Study to Evaluate the Efficacy, Immunogenicity, and Safety of RSVpreF in Adults. (RENOIR)

• ClinicalTrials.gov Identifier: NCT05035212
• Recruitment Status: Recruiting
• First Posted: September 5, 2021
• Last Update Posted: April 30, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: August 20, 2021
• First Posted Date: September 5, 2021
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: August 31, 2021
• Estimated Primary Completion Date: June 12, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2023)

• Efficacy Study: Number of first episode of RSV-associated lower respiratory tract illness (LRTI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. LRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. LRTI-RSV is defined as an ARI with 3 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Efficacy Study: Proportion of participants reporting prompted local reactions within 7-days after vaccination [ Time Frame: Within 7 days after vaccination ]
  Local reactions included pain at injection site, redness and swelling recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm and severe: >10 cm. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfere with daily activity and severe: prevented daily activity
• Efficacy Study: Proportion of participants reporting prompted systemic events within 7-days after vaccination [ Time Frame: Within 7 days after vaccination ]
  Systemic reactions:fever, fatigue/tiredness, headache, nausea, muscle pain, joint pain, vomiting, diarrhea and any systemic event recorded by participants in an e-diary. Fever: greater than equal to (>=)38.0 degrees (deg) Celsius (C), mild (>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C), moderate (>38.9 to 40.0 deg C and >40.0 deg C), severe (>38.9 deg C to 40.0 deg C) and grade 4 (>40.0 deg C). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h and severe: requires intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h.
• Efficacy Study: Proportion of participants reporting AE within 1-month after vaccination [ Time Frame: Within 1 month after vaccination (up to 35 days) ]
  An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events.
• Efficacy Study: Proportion of participants reporting SAE throughout the study [ Time Frame: Throughout the study duration (an average of 30 months) ]
  SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
• Efficacy Study: Proportion of participants reporting NDCMC throughout the study [ Time Frame: Throughout the study duration (an average of 30 months) ]
  An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
• SSA: Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers from participants who received 2-dose of RSVpreF [ Time Frame: Before revaccination and 1, 6, 12 and 18-months after revaccination with RSVpreF in SSA ]
  RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.
• SSA: Proportion of participants reporting prompted local reactions within 7-days after revaccination [ Time Frame: Within 7 days after revaccination ]
  Local reactions included pain at injection site, redness and swelling recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm and severe: >10 cm. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfere with daily activity and severe: prevented daily activity
• SSA: Proportion of participants reporting prompted systemic events within 7-days after revaccination [ Time Frame: Within 7 days after revaccination ]
  Systemic reactions:fever, fatigue/tiredness, headache, nausea, muscle pain, joint pain, vomiting, diarrhea and any systemic event recorded by participants in an e-diary. Fever: greater than equal to (>=)38.0 degrees (deg) Celsius (C), mild (>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C), moderate (>38.9 to 40.0 deg C and >40.0 deg C), severe (>38.9 deg C to 40.0 deg C) and grade 4 (>40.0 deg C). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h and severe: requires intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h.
• SSA: Proportion of participants reporting AE within 1-month after revaccination [ Time Frame: Within 1 month after revaccination (up to 35 days) ]
  An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events.
• SSA: Proportion of participants reporting SAE throughout the study [ Time Frame: Throughout the study duration (approximately 18 months) ]
  SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
• SSA: Proportion of participants reporting NDCMC throughout the study [ Time Frame: Throughout the study duration (approximately 18 months) ]
  An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
• SSB: Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers from participants who received 2-dose of RSVpreF [ Time Frame: Before revaccination and 1, 6, 12 and 18-months after revaccination with RSVpreF in SSB ]
  RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.
• SSB: Proportion of participants reporting prompted local reactions within 7-days after revaccination [ Time Frame: Within 7 days after revaccination ]
  Local reactions included pain at injection site, redness and swelling recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm and severe: >10 cm. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfere with daily activity and severe: prevented daily activity.
• SSB: Proportion of participants reporting prompted systemic events within 7-days after revaccination [ Time Frame: SSB: Proportion of participants reporting prompted systemic events within 7-days after revaccination ]
  Systemic reactions:fever, fatigue/tiredness, headache, nausea, muscle pain, joint pain, vomiting, diarrhea and any systemic event recorded by participants in an e-diary. Fever: greater than equal to (>=)38.0 degrees (deg) Celsius (C), mild (>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C), moderate (>38.9 to 40.0 deg C and >40.0 deg C), severe (>38.9 deg C to 40.0 deg C) and grade 4 (>40.0 deg C). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h and severe: requires intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h.
• SSB: Proportion of participants reporting AE within 1-month after revaccination [ Time Frame: Within 1 month after revaccination (up to 35 days) ]
  An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events.
• SSB: Proportion of participants reporting SAE throughout the study [ Time Frame: Throughout the study duration (approximately 18 months) ]
  SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
• SSB: Proportion of participants reporting NDCMC throughout the study [ Time Frame: Throughout the study duration (approximately 18 months) ]
  An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).

Original Primary Outcome Measures (submitted: August 30, 2021)

• Number of first episode of RSV-associated moderate to severe lower respiratory tract illness (msLRTI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. msLRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Proportion of participants reporting prompted local reactions within 7-days after vaccination [ Time Frame: Within 7 days after vaccination ]
  Local reactions included pain at injection site, redness and swelling recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm and severe: >10 cm. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfere with daily activity and severe: prevented daily activity
• Proportion of participants reporting prompted systemic events within 7-days after vaccination [ Time Frame: Within 7 days after vaccination ]
  Systemic reactions:fever, fatigue/tiredness, headache, nausea, muscle pain, joint pain, vomiting, diarrhea and any systemic event recorded by participants in an e-diary. Fever: greater than equal to (>=)38.0 degrees (deg) Celsius (C), mild (>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C), moderate (>38.9 to 40.0 deg C and >40.0 deg C), severe (>38.9 deg C to 40.0 deg C) and grade 4 (>40.0 deg C). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h and severe: requires intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h.
• Proportion of participants reporting AE within 1-month after vaccination [ Time Frame: Within 1 month after vaccination (up to 35 days) ]
  An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events.
• Proportion of participants reporting SAE throughout the study [ Time Frame: Throughout the study duration (an average of 30 months) ]
  SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
• Proportion of participants reporting NDCMC throughout the study [ Time Frame: Throughout the study duration (an average of 30 months) ]
  An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).

Current Secondary Outcome Measures (submitted: October 3, 2023)

• Efficacy Study: Number of first episode of RSV-associated severe LRTI (sLRTI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as LRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to LRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
• Efficacy Study: Number of first episode of LRTI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. LRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. LRTI-RSV is defined as an ARI with 3 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Efficacy Study: Number of first episode of LRTI-RSV across 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. LRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. LRTI-RSV is defined as an ARI with 3 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Efficacy Study: Number of first episode of RSV-associated ARI (ARI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Efficacy Study: Number of first episode of ARI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Efficacy Study: Number of first episode of ARI-RSV across 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Efficacy Study: Number of first episode of sLRTI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as LRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to LRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
• Efficacy Study: Number of first episode of sLRTI-RSV across 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as LRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to LRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
• Efficacy Study: Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers [ Time Frame: Before vaccination, 1-month after vaccination, before season 2 (approximately 12 months after vaccination) ]
  RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.
• SSA: Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers from participants who received placebo in SSA. [ Time Frame: Before revaccination and 1, 6, 12 and 18-months after revaccination with placebo in SSA ]
  RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.
• SSA: Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers from participants who received RSVpreF in SSA. [ Time Frame: 1 month after receiving the initial vaccination in the efficacy study and 1 month after revaccination in SSA ]
  RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.
• SSB: Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers from participants who received placebo in SSB [ Time Frame: Before revaccination and 1, 6, 12 and 18-months after revaccination with placebo in SSB ]
  RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.
• SSB: Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers from participants who received RSVpreF in SSB. [ Time Frame: 1 month after receiving the initial vaccination in the efficacy study and 1 month after revaccination in SSB ]
  RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.

Original Secondary Outcome Measures (submitted: August 30, 2021)

• Number of first episode of msLRTI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. msLRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of msLRTI-RSV in the third RSV season [ Time Frame: During the third RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. msLRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of msLRTI-RSV through first 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. msLRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of msLRTI-RSV across 3 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 3 visit (an average of 18 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. msLRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of RSV-associated ARI (ARI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of ARI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of ARI-RSV in the third RSV season [ Time Frame: During the third RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of ARI-RSV through first 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of ARI-RSV across 3 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 3 visit (an average of 18 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
• Number of first episode of RSV-associated severe LRTI (sLRTI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as msLRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to msLRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
• Number of first episode of sLRTI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as msLRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to msLRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
• Number of first episode of sLRTI-RSV in the third RSV season [ Time Frame: During the third RSV season (an average of 6 months) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as msLRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to msLRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
• Number of first episode of sLRTI-RSV through first 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as msLRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to msLRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
• Number of first episode of sLRTI-RSV across 3 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 3 visit (an average of 18 months of surveillance) ]
  Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as msLRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to msLRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
• Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers [ Time Frame: Before vaccination, 1-month after vaccination, before season 2 (approximately 12 months after vaccination), before season 3 (approximately 24 months after vaccination) ]
  RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.
• RSV prefusion-F-binding specific antibody responses (IgG) [ Time Frame: Before vaccination, 1-month after vaccination, before season 2 (approximately 12 months after vaccination), before season 3 (approximately 24 months after vaccination) ]
  RSV prefusion-F-binding specific antibody responsee IgG, expressed as Geometric Mean Concentrations (GMCs), and GMFR. The IgG were quantified for RSV A and RSV B separately by incubating test sample sera with streptavidin-coated Luminex.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Efficacy, Immunogenicity, and Safety of RSVpreF in Adults.
• Official Title: A PHASE 3 STUDY TO EVALUATE THE EFFICACY, IMMUNOGENICITY, AND SAFETY OF RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F SUBUNIT VACCINE IN ADULTS

Brief Summary

Efficacy Study: This randomized, double-blinded, placebo-controlled Phase 3 study is designed to assess the safety, immunogenicity, and efficacy of a single dose of RSVpreF in the prevention of LRTI-RSV in adults:

• At a dose of 120µg.
• In adults 60 years of age and older.
• The duration of the study for each participant will be up to approximately 24 months.
• The study will be conducted in the United States, Canada, Netherlands, Finland, Argentina, Japan and South Africa.

Substudy A: This study is an extension of the efficacy study and was designed to evaluate the safety and immunogenicity of a second dose of RSVpreF when administered after a dosing interval of approximately 2 years:

• At a dose of 120µg (as studied in the Phase 3 Efficacy Study)
• Blood samples will be collected for antibody testing.
• The duration of the study for each participant will be up to approximately 18 months.
• The study will be conducted in the United States and Argentina.

Substudy B: This study was designed to evaluate the safety and immunogenicity of a second dose of RSVpreF when administered after a dosing interval of approximately 1 year:

• At a dose of 120µg (as studied in the Phase 3 Efficacy Study)
• Blood samples will be collected for antibody testing.
• The duration of the study for each participant will be up to approximately 18 months.
• The study will be conducted in Argentina.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

This is a double-blinded, placebo-controlled study.

Primary Purpose: Prevention

• Condition: Lower Respiratory Tract Illness

Intervention

• Biological: RSVpreF
  RSV vaccine (RSVpreF)
• Biological: Placebo
  Placebo

Study Arms

• Experimental: Efficacy Study: RSVpreF vaccine
  RSVpreF
  Intervention: Biological: RSVpreF
• Placebo Comparator: Efficacy Study: Placebo dose
  Placebo
  Intervention: Biological: Placebo
• Experimental: SSA: Vaccination of RSVpreF recipients with RSVpreF
  Participants who originally received RSVpreF in the Efficacy Study and are eligible for SSA will receive RSVpreF in SSA.
  Intervention: Biological: RSVpreF
• Placebo Comparator: SSA: Vaccination of RSVpreF recipients with Placebo
  Participants who originally received RSVpreF in the Efficacy Study and are eligible for SSA will receive Placebo in SSA.
  Intervention: Biological: Placebo
• Experimental: SSB: Vaccination of RSVpreF recipients with RSVpreF
  Participants who originally received RSVpreF in the Efficacy Study and are eligible for SSB will receive RSVpreF in SSB.
  Intervention: Biological: RSVpreF
• Placebo Comparator: SSB: Vaccination of RSVpreF recipients with Placebo
  Participants who originally received RSVpreF in the Efficacy Study and are eligible for SSB will receive Placebo in SSB.
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 29, 2024): 45000
• Original Estimated Enrollment (submitted: August 30, 2021): 30000
• Estimated Study Completion Date: June 12, 2026
• Estimated Primary Completion Date: June 12, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Efficacy Study

Inclusion Criteria:

• Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, frequent symptom assessment by mobile device application, and other study procedures, including collection of nasal swabs by themselves and by study staff when indicated.
• Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.

Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for participants with known stable infection with HIV, HCV, or HBV can be found in the protocol.

• Adults who are ambulatory and live in the community, or in assisted living or long-term care residential facilities that provide minimal assistance, such that the participant is primarily responsible for self-care and activities of daily living.
• Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

• Male or female participants ≥60 years of age.

  • Male participants able to father children must agree to use a highly effective method of contraception from the time of informed consent through at least 28 days after study intervention administration.
  • Female participants must not be of childbearing potential.

Exclusion Criteria:

• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine.
• Serious chronic disorder including metastatic malignancy, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the participant from participating in the study.
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Participation in other studies involving an investigational product within 28 days prior to consent and/or through and including the 6-months follow-up visit (Visit 3).

Note: This criterion does not apply to participants who are participating in a follow-up period for another study involving a study intervention that is an investigational drug or vaccine, if receipt of the last dose was at least 6 months prior to consenting for this study and there is no further dosing anticipated from the previous study during the participant's participation in this study

- Individuals who receive chronic systemic treatment with immunosuppressive therapy, including cytotoxic agents, monoclonal antibodies, systemic corticosteroids, or radiotherapy, eg, for cancer or an autoimmune disease, from 60 days before study intervention administration or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled in the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

Note: Participants with COPD or asthma can be enrolled if chronic corticosteroids do not exceed a dose equivalent to 10 mg/day of prednisone.

• Receipt of blood/plasma products or immunoglobulin within 60 days before study intervention administration.
• Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Substudy A

Inclusion Criteria:

• Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, frequent symptom assessment by mobile device application, and other study procedures, including collection of nasal swabs by themselves and by study staff when indicated.
• Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.

Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for participants with known stable infection with HIV, HCV, or HBV can be found in the protocol.

• Adults who are ambulatory and live in the community, or in assisted living or long-term care residential facilities that provide minimal assistance, such that the participant is primarily responsible for self-care and activities of daily living.
• Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

• Male or female participants ≥60 years of age.

  • Male participants able to father children must agree to use a highly effective method of contraception from the time of informed consent through at least 28 days after study intervention administration.
  • Female participants must not be of childbearing potential.
• Participants who received RSVpreF in the efficacy study.
• Participants who have a Visit 2 serology sample available for testing from the efficacy study, completed the end-of-Season 2 visit (Visit 5), and did not meet exclusion criteria throughout the efficacy study duration.

Exclusion Criteria:

• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine.
• Serious chronic disorder including metastatic malignancy, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the participant from participating in the study.
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Participation in other studies involving an investigational product within 28 days prior to consent and/or through and including the 6-months follow-up visit (Visit 103).

Note: This criterion does not apply to participants who are participating in a follow-up period for another study involving a study intervention that is an investigational drug or vaccine, if receipt of the last dose was at least 6 months prior to consenting for this study and there is no further dosing anticipated from the previous study during the participant's participation in this study - Individuals who receive chronic systemic treatment with immunosuppressive therapy, including cytotoxic agents, monoclonal antibodies, systemic corticosteroids, or radiotherapy, eg, for cancer or an autoimmune disease, from 60 days before study intervention administration or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled in the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

Note: Participants with COPD or asthma can be enrolled if chronic corticosteroids do not exceed a dose equivalent to 10 mg/day of prednisone.

• Receipt of blood/plasma products or immunoglobulin within 60 days before study intervention administration.
• Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.

Note: This criterion does not include the receipt of RSVpreF in the efficacy study. Per inclusion criterion #6, receipt of RSVpreF in the efficacy study is required to participate in Substudy A.

• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
• Participant was confirmed by the sponsor to have previously received the study intervention more than once.

Substudy B

Inclusion Criteria:

• Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, frequent symptom assessment by mobile device application, and other study procedures, including collection of nasal swabs by themselves and by study staff when indicated.
• Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.

Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for participants with known stable infection with HIV, HCV, or HBV can be found in the protocol.

• Adults who are ambulatory and live in the community, or in assisted living or long-term care residential facilities that provide minimal assistance, such that the participant is primarily responsible for self-care and activities of daily living.
• Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

• Male or female participants ≥60 years of age.

  • Male participants able to father children must agree to use a highly effective method of contraception from the time of informed consent through at least 28 days after study intervention administration.
  • Female participants must not be of childbearing potential. 6. Participants who received RSVpreF in the efficacy study.
• Participants who received RSVpreF in the efficacy study.
• Participants who have a Visit 2 serology sample available for testing from the efficacy study and did not meet exclusion criteria through Visit 4 of the efficacy study.

Exclusion Criteria:

• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine.
• Serious chronic disorder including metastatic malignancy, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the participant from participating in the study.
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Participation in other studies involving an investigational product within 28 days prior to consent and/or through and including the 6-months follow-up visit (Visit 203).

Note: This criterion does not apply to participants who are participating in a follow-up period for another study involving a study intervention that is an investigational drug or vaccine, if receipt of the last dose was at least 6 months prior to consenting for this study and there is no further dosing anticipated from the previous study during the participant's participation in this study

- Individuals who receive chronic systemic treatment with immunosuppressive therapy, including cytotoxic agents, monoclonal antibodies, systemic corticosteroids, or radiotherapy, eg, for cancer or an autoimmune disease, from 60 days before study intervention administration or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled in the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

Note: Participants with COPD or asthma can be enrolled if chronic corticosteroids do not exceed a dose equivalent to 10 mg/day of prednisone.

• Receipt of blood/plasma products or immunoglobulin within 60 days before study intervention administration.
• Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.

Note: This criterion does not include the receipt of RSVpreF in the efficacy study. Per inclusion criterion #6, receipt of RSVpreF in the efficacy study is required to participate in Substudy B.

• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
• Participant was confirmed by the sponsor to have previously received the study intervention more than once.
• Participants who completed Vaccination 1 from the efficacy study less than 9 months or greater than 15 months prior to revaccination.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Argentina, Canada, Finland, Japan, Netherlands, South Africa, United States

Administrative Information

• NCT Number: NCT05035212
• Other Study ID Numbers: C3671013; 2021-003693-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2024