EPIC-Peds: A Study to Learn About the Study Medicine Called PF-07321332 (Nirmatrelvir)/Ritonavir in Patients Under 18 Years of Age With COVID-19 That Are Not Hospitalized But Are at Risk for Severe Disease

• ClinicalTrials.gov Identifier: NCT05261139
• Recruitment Status: Suspended
• First Posted: March 2, 2022
• Last Update Posted: April 3, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: February 25, 2022
• First Posted Date: March 2, 2022
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: March 7, 2022
• Estimated Primary Completion Date: July 3, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 7, 2023)

• Cohort 1-2: Maximum Observed Plasma Concentration (Cmax) of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 4: pre-dose; Day 5: pre-dose, and 1, 2, 4, 6, 8 and 10 hours post dose ]
  Pharmacokinetic (PK) sample(s) for Cohorts 1-2 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (10 to 13 total PK samples for Cohort 1 and 10 samples for Cohort 2). Day 1: 1 hour-post dose by Tasso device and venous blood Day 4: pre-dose (Tasso) Day 5: pre-dose, and 1, 2, 4, 6, 8 and 10 hours post AM dose (Tasso); for Cohort 1 pre-dose, and 1, 2 hours post AM dose venous samples in approximately 10 participants.
• Cohort 1-2: Area Under the Curve to the End of the Dosing Period (AUC0-tau) of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 4: pre-dose; Day 5: pre-dose, and 1, 2, 4, 6, 8 and 10 hours post dose ]
  Pharmacokinetic (PK) sample(s) for Cohorts 1-2 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (10 to 13 total PK samples for Cohort 1 and 10 samples for Cohort 2). Day 1: 1 hour-post dose by Tasso device and venous blood Day 4: pre-dose (Tasso) Day 5: pre-dose, and 1, 2, 4, 6, 8 and 10 hours post AM dose (Tasso); for Cohort 1 pre-dose, and 1, 2 hours post AM dose venous samples in approximately 10 participants.
• Cohort 3: Maximum Observed Plasma Concentration (Cmax) of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 2: 2-8 hours post dose; Day 3: 2-8 hours post dose; Day 4: 2-8 hours post dose; Day 5: PK pre-dose and post-dose 1 to 3 hours ]
  PK sample(s) Cohort 3 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (7 total samples) Day 1: 1 hour-post dose Tasso and venous blood. Day 2: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 3: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 4: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 5: PK pre-dose and post-dose between 1 to 3 hours (Tasso)
• Cohort 3: Area Under the Curve to the End of the Dosing Period (AUC0-tau) of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 2: 2-8 hours post dose; Day 3: 2-8 hours post dose; Day 4: 2-8 hours post dose; Day 5: PK pre-dose and post-dose 1 to 3 hours ]
  PK sample(s) Cohort 3 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (7 total samples) Day 1: 1 hour-post dose Tasso and venous blood. Day 2: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 3: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 4: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 5: PK pre-dose and post-dose between 1 to 3 hours (Tasso)
• Cohort 4-5: Maximum Observed Plasma Concentration (Cmax) of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 5: PK pre-dose and post-dose AM between 1 to 3 hours ]
  PK sample(s) Cohorts 4-5 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (4 total samples) Day 1: 1 hour-post dose Tasso and 1 venous blood. Day 5: PK pre-dose and post-dose AM between 3 to 5 hours (Tasso)
• Cohort 4-5: Area Under the Curve to the End of the Dosing Period (AUC0-tau) of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 5: PK pre-dose and post-dose AM between 1 to 3 hours ]
  PK sample(s) Cohorts 4-5 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (4 total samples) Day 1: 1 hour-post dose Tasso and 1 venous blood. Day 5: PK pre-dose and post-dose AM between 3 to 5 hours (Tasso)
• Incidence of Treatment Emergent Adverse Events (TEAEs) leading to discontinuations. [ Time Frame: From Baseline up through Day 34 ]
• Incidence of Serious Adverse Events (SAEs) leading to discontinuations. [ Time Frame: From Baseline up through Day 34 ]
• Incidence of Adverse Events (AEs) leading to discontinuations. [ Time Frame: From Baseline up through Day 34 ]
• Number of participants with change from Baseline in Vital Signs [ Time Frame: From Baseline up through Day 34 ]

Original Primary Outcome Measures (submitted: February 28, 2022)

• Cohort 1-2: Maximum Observed Plasma Concentration (Cmax) of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 4: pre-dose or trough; Day 5: pre-dose or trough, and 1, 2, 4, 6, 8, and 10 hours post dose ]
  Pharmacokinetic (PK) sample(s) for Cohorts 1-2 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (10 total PK samples) Day 1: 1 hour-post dose by Tasso device and 1 mL venous blood Day 4: pre-dose or trough (Tasso only) Day 5: pre-dose or trough, and 1, 2, 4, 6, 8, and 10 hours post AM dose (Tasso only)
• Cohort 3-5: Cmax of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 2: 2-8 hours post dose; Day 3: 2-8 hours post dose; Day 4: 2-8 hours post dose; Day 5: PK trough and post-dose 1 to 3 hours ]
  PK sample(s) Cohorts 3-5 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (7 total samples) Day 1: 1 hour-post dose Tasso and 1 mL venous blood. Day 2: 2-8 hours post AM dose prior to PM dose (Tasso only) Day 3: 2-8 hours post AM dose prior to PM dose (Tasso only) Day 4: 2-8 hours post AM dose prior to PM dose (Tasso only) Day 5: PK trough and post-dose 1 to 3 hours (Tasso only)
• Cohort 1-2: Area Under the Curve to the End of the Dosing Period (AUC0-tau) of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 4: pre-dose or trough; Day 5: pre-dose or trough, and 1, 2, 4, 6, 8, and 10 hours post dose ]
  Pharmacokinetic (PK) sample(s) for Cohorts 1-2 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (10 total PK samples) Day 1: 1 hour-post dose by Tasso device and 1 mL venous blood Day 4: pre-dose or trough (Tasso only) Day 5: pre-dose or trough, and 1, 2, 4, 6, 8, and 10 hours post AM dose (Tasso only)
• Cohort 3-5: AUC0-tau of nirmatrelvir and ritonavir [ Time Frame: Day 1: 1 hour-post dose; Day 2: 2-8 hours post dose; Day 3: 2-8 hours post dose; Day 4: 2-8 hours post dose; Day 5: PK trough and post-dose 1 to 3 hours ]
  PK sample(s) Cohorts 3-5 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (7 total samples) Day 1: 1 hour-post dose Tasso and 1 mL venous blood. Day 2: 2-8 hours post AM dose prior to PM dose (Tasso only) Day 3: 2-8 hours post AM dose prior to PM dose (Tasso only) Day 4: 2-8 hours post AM dose prior to PM dose (Tasso only) Day 5: PK trough and post-dose 1 to 3 hours (Tasso only)
• Incidence of TEAEs, SAEs, AEs leading to discontinuations, and vital sign measurements [ Time Frame: From Baseline up through Day 34 ]

Current Secondary Outcome Measures (submitted: August 7, 2023)

• Viral load assessment titers measured via reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal or nasal swabs over time [ Time Frame: Baseline, Day 4, 5, 6, 10, 14 and 28 ]
  To evaluate the change in viral loads in pediatric participants from birth to <18 years of age with COVID-19 who are at risk of progression to severe disease.
• Proportion of participants with COVID-19 related hospitalization or death from any cause [ Time Frame: From Baseline through Day 28 ]
  To evaluate the efficacy of nirmatrelvir/ritonavir for the treatment of COVID-19 in nonhospitalized symptomatic pediatric participants with COVID-19 who are at increased risk of progression to severe disease.
• Patient assessment on acceptability and palatability of nirmatrelvir/ritonavir (film-coated tablets and oral powder) [ Time Frame: At baseline only for tablets and after each dose for powder formulation ]
  Frequency of responses to visual questionnaire on taste.

Original Secondary Outcome Measures (submitted: February 28, 2022)

• Viral load assessment titers measured via reverse transcription polymerase chain reaction (RT-PCR) in nasal swabs over time [ Time Frame: Baseline, Day 4, 5, 6, 10, and 14 ]
  To evaluate the change in viral loads in pediatric participants from birth to <18 years of age with COVID-19 who are at risk of progression to severe disease.
• Proportion of participants with COVID-19 related hospitalization or death from any cause [ Time Frame: From Baseline through Day 28 ]
  To evaluate the efficacy of nirmatrelvir/ritonavir for the treatment of COVID-19 in nonhospitalized symptomatic pediatric participants with COVID-19 who are at increased risk of progression to severe disease.
• Patient assessment on palatability of nirmatrelvir (film-coated tablets and age-appropriate formulation) [ Time Frame: At baseline only ]
  Frequency of responses to visual questionnaire on taste.
• Patient assessment on palatability of ritonavir (age-appropriate formulation) [ Time Frame: At baseline only ]
  Frequency of responses to visual questionnaire on taste.
• Patient assessment on acceptability of nirmatrelvir (film-coated tablets and age-appropriate formulation) [ Time Frame: At baseline only ]
  Frequency of responses to visual questionnaire swallowability
• Patient assessment on acceptability of ritonavir (age-appropriate formulation) [ Time Frame: At baseline only ]
  Frequency of responses to visual questionnaire swallowability

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

Descriptive Information

• Brief Title: EPIC-Peds: A Study to Learn About the Study Medicine Called PF-07321332 (Nirmatrelvir)/Ritonavir in Patients Under 18 Years of Age With COVID-19 That Are Not Hospitalized But Are at Risk for Severe Disease
• Official Title: A PHASE 2/3, INTERVENTIONAL SAFETY, PHARMACOKINETICS, AND EFFICACY, OPEN-LABEL, MULTI-CENTER, SINGLE-ARM STUDY TO INVESTIGATE ORALLY ADMINISTERED PF-07321332 (NIRMATRELVIR)/RITONAVIR IN NONHOSPITALIZED SYMPTOMATIC PEDIATRIC PARTICIPANTS WITH COVID-19 WHO ARE AT RISK OF PROGRESSION TO SEVERE DISEASE

Brief Summary

The purpose of this clinical trial is to learn about the safety, pharmacokinetics (pharmacokinetics helps us understand how the drug is changed and eliminated from your body after you take it), and efficacy (how well a study treatment works in the study) of the study medicine (called nirmatrelvir/ritonavir) for potential treatment of coronavirus disease 2019 (COVID-19).

The study medicine will be given to patients under 18 years of age with COVID-19 that are not hospitalized but are at risk for severe disease.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: nirmatrelvir
  PF-07321332
• Drug: ritonavir
  ritonavir

Study Arms

• Experimental: Cohort 1 nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will be given by tablets or powder by mouth twice a day for 5 days (10 doses total).

  Weight ≥40 kg

  1. ≥12 to <18 years
  2. ≥6 to <12 years
  Interventions:

  • Drug: nirmatrelvir
  • Drug: ritonavir
• Experimental: Cohort 2 nirmatrelvir/ritonavir
  nirmatrelvir/ritonavir will be given as powder by mouth twice a day for 5 days (10 doses total) Weight ≥20 to <40 kg, ≥6 to <18 years
  Interventions:

  • Drug: nirmatrelvir
  • Drug: ritonavir
• Experimental: Cohort 3 nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir

  ≥2 to <6 years

  Interventions:

  • Drug: nirmatrelvir
  • Drug: ritonavir
• Experimental: Cohort 4 nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir

  ≥1 month (≥28 days) to <2 years

  Interventions:

  • Drug: nirmatrelvir
  • Drug: ritonavir
• Experimental: Cohort 5 nirmatrelvir/ritonavir
  nirmatrelvir/ritonavir <1 month (<28 days) old
  Interventions:

  • Drug: nirmatrelvir
  • Drug: ritonavir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: August 7, 2023): 160
• Original Estimated Enrollment (submitted: February 28, 2022): 140
• Estimated Study Completion Date: July 3, 2027
• Estimated Primary Completion Date: July 3, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

• Male and female, age 0 to < 18 years, able to swallow for some participants
• Confirmed SARS-CoV-2 infection within 72 hours prior to enrollment
• Initial onset of COVID-19 signs/symptoms within 5 days prior to the day of enrollment and at least 1 of the specified COVID-19 signs/symptoms present at enrollment
• Has at least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19

Exclusion Criteria:

• History of or need for hospitalization for the medical treatment of COVID-19
• Total bilirubin >=2X upper limit of normal (ULN) (except for Gilbert's syndrome)
• Receiving dialysis or have known moderate to severe renal impairment
• Suspected or confirmed concurrent active systemic infection other than COVID-19
• History of hypersensitivity or other contraindication to any of the components of the study intervention
• Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance or strong inducers of cytochrome P450 (CYP)3A4
• Has received or is expected to receive antibody treatment, antiviral treatment or convalescent COVID-19 plasma
• Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19 through the study follow up
• Females who are pregnant or breastfeeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Hungary, Japan, Mexico, Puerto Rico, South Africa, United Kingdom, United States

Administrative Information

• NCT Number: NCT05261139
• Other Study ID Numbers: C4671026
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

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