A Study to Evaluate the Long-Term Safety and Efficacy of Bimekizumab in Subjects With Psoriatic Arthritis (BE ACTIVE 2)

• ClinicalTrials.gov Identifier: NCT03347110
• Recruitment Status: Completed
• First Posted: November 20, 2017
• Results First Posted: December 1, 2023
• Last Update Posted: December 1, 2023
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Tracking Information

• First Submitted Date: November 15, 2017
• First Posted Date: November 20, 2017
• Results First Submitted Date: October 26, 2023
• Results First Posted Date: December 1, 2023
• Last Update Posted Date: December 1, 2023
• Actual Study Start Date: November 22, 2017
• Actual Primary Completion Date: October 29, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 26, 2023)

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Study [ Time Frame: From Entry Visit of PA0009 until Safety Follow-Up Visit (up to Week 120) ]
  An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs were defined as events with onset date on or after the start date of study medication in PA0009.
• Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Study [ Time Frame: From Entry Visit of PA0009 until Safety Follow-Up Visit (up to Week 120) ]
  A serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, life-threatening, significant or persistent disability/incapacity, congenital anomaly/birth defect, important medical event, initial inpatient hospitalization or prolongation of hospitalization.

Original Primary Outcome Measures (submitted: November 15, 2017)

• Incidence of Adverse Event (AE) during the study [ Time Frame: From Entry Visit (Visit 1) until Safety Follow-Up Visit (up to Week 120) ]
  An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
• Incidence of Serious Adverse Event (SAE) during the study [ Time Frame: From Entry Visit (Visit 1) until Safety Follow-Up Visit (up to Week 120) ]
  Once it is determined that a subject experienced an Adverse Event (AE), the seriousness of the AE must be determined. An SAE must meet 1 or more of the following criteria: death, life-threatening, significant or persistent disability/incapacity, congenital anomaly/birth defect, important medical event, initial inpatient hospitalization or prolongation of hospitalization.) product.

Current Secondary Outcome Measures (submitted: October 26, 2023)

• Percentage of Participants Who Withdrew Due to Treatment-emergent Adverse Event (TEAE) During the Study [ Time Frame: From Entry Visit of PA0009 until Safety Follow-Up Visit (up to Week 120) ]
  An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
• Percentage of Participants With American College of Rheumatology 20% Improvement (ACR20) Response at Week 48 Calculated Relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The ACR20 response rate was based on 20% or greater improvement relative to Baseline of PA0008 in the following measures: Tender Joint Count (TJC) based on 78 joints, Swollen Joint Count (SJC) based on 76 joints; 3 of the 5 remaining core set measures: Disease activity as assessed by Patient's Global Assessment of Disease Activity (PGADA), Disease activity as assessed by Physician's Global Assessment of Disease Activity (PhGADA), Pain as assessed by Patient's Assessment of Arthritis Pain (PtAAP), Physical function as assessed by Health Assessment Questionnaire - Disability Index (HAQ-DI), Acute phase response as assessed by high sensitivity C-reactive protein (hs CRP). Participants for whom ACR could not be derived due to missing data were counted as non-responders as per NRI analysis.
• Percentage of Participants With American College of Rheumatology 50% Improvement (ACR50) Response at Week 48 Calculated Relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The ACR50 response rate was based on 50% or greater improvement relative to Baseline of PA0008 in the following measures: TJC based on 78 joints, SJC based on 76 joints; 3 of the 5 remaining core set measures: Disease activity as assessed by PGADA, Disease activity as assessed by PhGADA, Pain as assessed by PtAAP, Physical function as assessed by HAQ-DI, Acute phase response as assessed by hs CRP. Participants for whom ACR could not be derived due to missing data were counted as non-responders as per NRI analysis.
• Percentage of Participants With American College of Rheumatology 70% Improvement (ACR70) Response at Week 48 Calculated Relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The ACR70 response rate was based on 70% or greater improvement relative to Baseline of PA0008 in the following measures: TJC based on 78 joints, SJC based on 76 joints; 3 of the 5 remaining core set measures: Disease activity as assessed by PGADA, Disease activity as assessed by PhGADA, Pain as assessed by PtAAP, Physical function as assessed by HAQ-DI, Acute phase response as assessed by hs CRP. Participants for whom ACR could not be derived due to missing data were counted as non-responders as per NRI analysis.
• Change From Baseline of PA0008 in Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) at Week 48 Calculated Relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The MASES is an index that measures the severity (ie, intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous process). Each item was scored as 0 = not tender or 1 = tender and then were summed for a possible score of 0 to 13, with higher scores indicating worse enthesitis. If 7 or more items were available, MASES was calculated by dividing the summed score with the number of assessments and multiplying the result by 13. If less than 7 items were available, MASES was treated as missing.
• Change From Baseline of PA0008 in the Leeds Dactylitis Index (LDI) at Week 48 Calculated Relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  Presence of dactylitis was assessed using the LDI basic which evaluated for a greater than or equal to (>=) 10% difference in the circumference of the digit compared to the opposite digit and was then multiplied by the tenderness score, using a simple grading system (0=absent, 1=present). The results from each digit with dactylitis were summed to produce a final score. For the final score, the minimum value for LDI is zero and there is no maximum value. A low score indicates less dactylitis symptoms. A score of zero is considered dactylitis free. Observed values have been reported in this outcome measure.
• Percentage of Participants With Psoriasis Area Severity Index (PASI75) Response at Week 48 Calculated Relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline of PA0008. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining percentage of skin covered with psoriasis (PSO) for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. For the Final score, minimum possible PASI value is 0= no disease, maximum value is 72= maximal disease. Missing PASI responses were imputed using least observation carried forward (LOCF) for any visits where the corresponding BSA has not increased compared to the preceding visit.
• Percentage of Participants With Psoriasis Area Severity Index (PASI90) Response at Week 48 Calculated Relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline of PA0008. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. For the final score, minimum possible PASI value is 0= no disease, maximum value is 72= maximal disease. Missing PASI responses were imputed using LOCF for any visits where the corresponding BSA has not increased compared to the preceding visit.

Original Secondary Outcome Measures (submitted: November 15, 2017)

• Subjects who withdrew due to an Adverse Event (AE) during the study [ Time Frame: From Entry Visit (Visit 1) until Safety Follow-Up Visit (up to Week 120) ]
  An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
• ACR20 (American College of Rheumatology 20% Improvement) Response at Week 48 calculated relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The ACR20 response rate is based on a 20% or greater improvement of arthritis relative to Baseline of PA0008.
• ACR20 (American College of Rheumatology 20% Improvement) Response at Week 48 calculated relative to PA0009 entry value [ Time Frame: PA0009 Entry Visit, Week 48 ]
  The ACR20 response rate is based on a 20% or greater improvement of arthritis relative to PA0009 entry value.
• ACR50 (American College of Rheumatology 50% Improvement) Response at Week 48 calculated relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The ACR50 response rate is based on a 50% or greater improvement of arthritis relative to Baseline of PA0008.
• ACR50 (American College of Rheumatology 50% Improvement) Response at Week 48 calculated relative to PA0009 entry value [ Time Frame: PA0009 Entry Visit, Week 48 ]
  The ACR50 response rate is based on a 50% or greater improvement of arthritis relative to PA0009 entry value.
• ACR70 (American College of Rheumatology 70% Improvement) Response at Week 48 calculated relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The ACR70 response rate is based on a 70% or greater improvement of arthritis relative to Baseline of PA0008.
• ACR70 (American College of Rheumatology 70% Improvement) Response at Week 48 calculated relative to PA0009 entry value [ Time Frame: PA0009 Entry Visit, Week 48 ]
  The ACR70 response rate is based on a 70% or greater improvement of arthritis relative to PA0009 entry value.
• Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) at Week 48 calculated relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The MASES is an index that measures the severity (ie, intensity and extent) of enthesitis through the assessment of 13 entheses each scored as 0 or 1 and then summed for a possible score of 0 to 13.
• Change from PA0009 entry value in Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) at Week 48 [ Time Frame: PA0009 Entry Visit, Week 48 ]
  The MASES is an index that measures the severity (ie, intensity and extent) of enthesitis through the assessment of 13 entheses each scored as 0 or 1 and then summed for a possible score of 0 to 13.
• Change from Baseline in the Leeds Dactylitis Index (LDI) at Week 48 calculated relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  Presence of dactylitis will be assessed using the LDI basic which evaluates for a >=10% difference in the circumference of the digit compared to the opposite digit this is then multiplied by the tenderness score, using a simple grading system (0=absent, 1=present).
• Change from PA0009 entry value in the Leeds Dactylitis Index (LDI)at Week 48 [ Time Frame: PA0009 Entry Visit, Week 48 ]
  Presence of dactylitis will be assessed using the LDI basic which evaluates for a >=10% difference in the circumference of the digit compared to the opposite digit this is then multiplied by the tenderness score, using a simple grading system (0=absent, 1=present).
• PASI75 (Psoriasis Area Severity Index) Response at Week 48 calculated relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The PASI75 response is based on at least 75% improvement in the PASI score compared to Baseline in PA0008. The Investigator assesses the average redness, thickness, and scaliness of lesions in each body area (each on a 5-point scale); 0=none, 1=slight, 2=moderate, 3=marked, and 4=very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity.
• PASI75 (Psoriasis Area Severity Index) Response at Week 48 calculated relative to PA0009 entry value [ Time Frame: PA0009 Entry Visit, Week 48 ]
  The PASI75 response is based on at least 75% improvement in the PASI score compared to PA0009 entry value. The Investigator assesses the average redness, thickness, and scaliness of lesions in each body area (each on a 5-point scale); 0=none, 1=slight, 2=moderate, 3=marked, and 4=very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity.
• PASI90 (Psoriasis Area Severity Index) Response at Week 48 calculated relative to Baseline of PA0008 [ Time Frame: Baseline of PA0008, Week 48 ]
  The PASI90 response is based on at least 90% improvement in the PASI score compared to Baseline in PA0008. The Investigator assesses the average redness, thickness, and scaliness of lesions in each body area (each on a 5-point scale); 0=none, 1=slight, 2=moderate, 3=marked, and 4=very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity.
• PASI90 (Psoriasis Area Severity Index) Response at Week 48 calculated relative to PA0009 entry value [ Time Frame: PA0009 Entry Visit, Week 48 ]
  The PASI90 response is based on at least 90% improvement in the PASI score compared to PA0009 entry value. The Investigator assesses the average redness, thickness, and scaliness of lesions in each body area (each on a 5-point scale); 0=none, 1=slight, 2=moderate, 3=marked, and 4=very marked. The PASI score ranges from 0 to 72 with a higher score indicating increased disease severity.

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

Descriptive Information

• Brief Title: A Study to Evaluate the Long-Term Safety and Efficacy of Bimekizumab in Subjects With Psoriatic Arthritis
• Official Title: A Multicenter, Open-Label, Follow-Up Study to Evaluate the Long-Term Safety and Efficacy of Bimekizumab in Subjects With Psoriatic Arthritis
• Brief Summary: This is a study to assess the long-term safety and tolerability of bimekizumab in subjects with psoriatic arthritis
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Psoriatic Arthritis

Intervention

Drug: Bimekizumab

Bimekizumab at a prespecified dose.

Other Name: UCB4940

Study Arms

Experimental: Bimekizumab

Subjects will receive bimekizumab up to 2 years.

Intervention: Drug: Bimekizumab

• Publications *: Mease PJ, Asahina A, Gladman DD, Tanaka Y, Tillett W, Ink B, Assudani D, de la Loge C, Coarse J, Eells J, Gossec L. Effect of bimekizumab on symptoms and impact of disease in patients with psoriatic arthritis over 3 years: results from BE ACTIVE. Rheumatology (Oxford). 2023 Feb 1;62(2):617-628. doi: 10.1093/rheumatology/keac353.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 25, 2018): 184
• Original Estimated Enrollment (submitted: November 15, 2017): 200
• Actual Study Completion Date: October 29, 2020
• Actual Primary Completion Date: October 29, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• In the opinion of the Investigator, the subject is expected to benefit from participation in an Open Label Extension (OLE) study
• Subject completed PA0008 without meeting any withdrawal criteria
• Female subjects must be postmenopausal, permanently sterilized or, if of childbearing potential, must be willing to use a highly effective method of contraception
• Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active

Exclusion Criteria:

• Female subjects who plan to become pregnant during the study or within 20 weeks following the last dose of IMP. Male subjects who are planning a partner pregnancy during the study or within 20 weeks following the last dose
• Subjects with any current sign or symptom that may indicate a medically significant active infection (except for the common cold) or has had an infection requiring systemic antibiotics within 2 weeks of study entry
• Subjects who meet any withdrawal criteria in PA0008. For any subject with an ongoing Serious Adverse Event, or a history of serious infections (including hospitalizations) in the lead-in study, the Medical Monitor must be consulted prior to the subject's entry into PA0009

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, Germany, Hungary, Poland, Russian Federation, United States

Administrative Information

• NCT Number: NCT03347110
• Other Study ID Numbers: PA0009; 2017-001003-74 ( EudraCT Number )
• Has Data Monitoring Committee: No

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.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• Original Responsible Party: UCB Biopharma S.P.R.L.
• Current Study Sponsor: UCB Biopharma SRL
• Original Study Sponsor: UCB Biopharma S.P.R.L.
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; +1 8445992273 (UCB)

• PRS Account: UCB Pharma
• Verification Date: November 2023