A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis

NCT05516758
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Phase
Phase 2
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Recruitment status
Terminated
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Participants
491
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Lead sponsor
Eli Lilly and Company
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Start date
2022-08-31
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Number of sites
131
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Summary
The main purpose of this study is to assess the safety and efficacy of peresolimab in adult participants with moderately-to-severely active rheumatoid arthritis.
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Acronym
RESOLUTION-1
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Short title
A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
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Official title
A Phase 2b, Double-Blind, Placebo-Controlled Study to Evaluate Peresolimab in Adult Participants With Moderately-to-Severely Active Rheumatoid Arthritis
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Terminated
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Phase
Phase 2
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Study type
Interventional
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Reason stopped
Study terminated due to an unfavourable benefit-risk profile observed in interim data analysis.
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Completion date
2025-01-17
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First posted
2022-08-26
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Registry last updated
2025-12-04
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Primary completion date
2023-11-20
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Start date
2022-08-31
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Actual participants
491
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Participants
491
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Participant count basis
Actual
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Protocol amendments
3
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Number of sites
131
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Eli Lilly and Company
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05516758
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ClinicalTrials.gov ID
NCT05516758
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Double masking
Masked roles
Participants, Investigators
Sources for study design
clinicaltrials.gov

  1. Percentage of Participants Achieving 20% Improvement in American College of Rheumatology Criteria (ACR20) Response at Week 12

    Timeframe: Week 12

    The ACR20 response was a composite measure of clinical, laboratory, and functional assessments used to evaluate improvement in rheumatoid arthritis signs and symptoms. ACR20 responders were participants with at least 20% improvement from baseline in tender joint count (TJC) and swollen joint count (SJC), and at least 20% improvement in 3 of the 5 remaining core measures: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) which measures participants' perceived degree of difficulty performing daily activities, and acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants achieving ACR20 response= (number of ACR20 responders)/ (number of participants analyzed) \*100.

  1. Percentage of Participants Achieving 50% Improvement in American College of Rheumatology Criteria (ACR50) Response at Week 12

    Timeframe: Week 12

    The ACR50 response was a composite measure of clinical, laboratory, and functional assessments used to evaluate improvement in rheumatoid arthritis signs and symptoms. ACR50 responders were participants with at least 50% improvement from baseline in TJC and SJC, and at least 50% improvement in 3 of the 5 remaining core measures: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, HAQ-DI which measures participants' perceived degree of difficulty performing daily activities, and acute phase reactant as measured by hsCRP. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100.

  2. Percentage of Participants Achieving 70% Improvement in American College of Rheumatology Criteria (ACR70) Response at Week 12

    Timeframe: Week 12

    The ACR70 response was a composite measure of clinical, laboratory, and functional assessments used to evaluate improvement in rheumatoid arthritis signs and symptoms. ACR70 responders were participants with at least 70% improvement from baseline in TJC and SJC, and at least 70% improvement in 3 of the 5 remaining core measures: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, HAQ-DI which measures participants' perceived degree of difficulty performing daily activities, and acute phase reactant as measured by hsCRP. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100.

  3. Percentage of Participants With Low Disease Activity (LDA) According to Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count-High-Sensitivity C-Reactive Protein (DAS28-hsCRP) ≤3.2 at Week 12

    Timeframe: Week 12

    DAS28-hsCRP LDA was defined as DAS28-hsCRP score of ≤3.2. The Disease Activity Score (DAS) based on 28 joint counts consisted of a composite numerical score derived from the following variables: tender joint count (0 to 28), swollen joint count (0 to 28), high-sensitivity C-reactive protein (hsCRP, mg/mL), and the patient's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28)+ 0.014\* participant's global assessment of disease activity+ 0.36\*natural log(hsCRP+1) + 0.96. Total Scores ranged from 1.0 to 9.4, with lower scores indicating less disease activity.

  4. Percentage of Participants With Remission According to DAS28-hsCRP Score <2.6 at Week 12

    Timeframe: Week 12

    DAS28-hsCRP remission is defined as DAS28-hsCRP \<2.6. DAS based on 28 joints consisted of composite numerical score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and patient's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP=0.56\*sqrt (TJC28) + 0.28\*sqrt (SJC28) + 0.014\* patient's global assessment of disease activity + 0.36\*natural log(hsCRP+1) +0.96. Total Scores ranged from 1.0-9.4, where lower scores indicated less disease activity.

  5. Percentage of Participants Achieving LDA According to Clinical Disease Activity Index (CDAI) Score ≤10 at Week 12

    Timeframe: Week 12

    Low disease activity was defined as a CDAI score of ≤10. CDAI is a tool for measurement of disease activity in rheumatoid arthritis that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity.

  6. Percentage of Participants Achieving Remission According to CDAI Score ≤2.8 at Week 12

    Timeframe: Week 12

    Remission was defined as a CDAI score of ≤2.8. CDAI is a tool for measurement of disease activity in rheumatoid arthritis that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity.

  7. Change From Baseline in DAS28-hsCRP Score at Week 12

    Timeframe: Baseline, Week 12

    DAS based on 28 joints consisted of composite numerical score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and patient's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP = 0.56\*sqrt (TJC28) + 0.28\*sqrt (SJC28)+ 0.014\* patient's global assessment of disease activity + 0.36\*natural log(hsCRP+1) +0.96. Total scores ranged 1.0-9.4; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition. Least Square (LS) Mean was calculated using mixed model repeated measures (MMRM) with treatment, stratification factors, baseline value, visit, treatment-by-visit interaction as fixed factors and participant as a random factor.

  8. Change From Baseline in CDAI Score at Week 12

    Timeframe: Baseline, Week 12

    CDAI is a tool for measurement of disease activity in rheumatoid arthritis that does not require laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity(scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity).CDAI is calculated by summing values of 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. Negative change from baseline indicates improvement. LS Mean was calculated using MMRM with treatment, stratification factors, baseline value, visit, treatment-by-visit interaction as fixed factors and participant as a random factor.

  9. Change From Baseline in HAQ-DI Score at Week 12

    Timeframe: Baseline, Week 12

    HAQ-DI was a patient-reported questionnaire used in rheumatoid arthritis to assess physical function over the past week. It covered 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2 to 3 items. Each item is scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity requiring assistance from another individual or the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Total score was computed as the sum of domain scores and divided by the number of domains answered. The total score ranges from 0 to 3, with higher scores indicating greater physical limitations. LS Mean was calculated using MMRM with treatment, stratification factors, baseline value, visit and treatment-by-visit interaction as fixed effects and participant as a random effect.

  10. Minimum Observed Concentration of Peresolimab by Treatment-Emergent Anti-Drug Antibody (TE ADA) Status

    Timeframe: Baseline through Week 12

    Minimum observed concentration of peresolimab was assessed and stratified by Treatment-Emergent Anti-Drug Antibody (TE-ADA) status (TE ADA positive and TE ADA negative). A TE ADA evaluable participant was defined as TE ADA positive if they met the following criteria: 1. Had baseline status of ADA Not Present and at least 1 postbaseline status of ADA Present with titer ≥ 2×minimum required dilution (MRD) of the ADA assay (Treatment Induced TE ADA). The MRD of peresolimab is 1:10. 2. Had baseline and postbaseline status of ADA Present, with the postbaseline titer being 2 dilutions (4-fold) greater than the baseline titer. TE-ADA negative participants were defined as those not meeting the TE ADA positive criteria.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • Have a diagnosis of adult onset rheumatoid arthritis (RA) for at least 3 months prior to screening, as defined by the 2010 ACR/European League Against Rheumatism (EULAR) classification criteria

  • Have moderately-to-severely active RA, at screening and baseline, defined by the presence of

    • ≥6 swollen joints based on 66 joint count, and
    • ≥6 tender joints based on 68 joint count.

  • Have had an inadequate response to, or loss of response or intolerance to at least 1 conventional synthetic DMARD (csDMARD), biologic DMARD ( bDMARD), or targeted synthetic DMARD (tsDMARD) treatment.

  • Have Class IV RA according to ACR revised criteria.

  • Have presence of 1 or more significant concurrent medical conditions per investigator judgment, including but not limited to

    • poorly controlled diabetes or hypertension

    • chronic kidney disease stage IIIb, IV, or V

    • symptomatic heart failure according to New York Heart Association Class II, III, or IV

    • myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack, within the past 12 months before randomization

    • severe chronic pulmonary disease, for example, requiring oxygen therapy

    • major chronic inflammatory disease or connective tissue disease other than RA, including but not limited to,

      • systemic lupus erythematosus
      • psoriatic arthritis
      • axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis
      • reactive arthritis
      • gout
      • scleroderma
      • polymyositis
      • dermatomyositis
      • active fibromyalgia, or
      • multiple sclerosis
Sources for eligibility
clinicaltrials.gov

  • Accel Research Sites - Birmingham Clinical Research UnitBirmingham, United States
  • Arizona Arthritis & Rheumatology Research PLLCGilbert, United States
  • Arizona Arthritis & Rheumatology Research, PLLCGlendale, United States
  • Arizona Arthritis & Rheumatology Research, PLLCMesa, United States
  • Arizona Arthritis & Rheumatology Associates, PLLCPhoenix, United States
  • Medvin Clinical Research - MetyasCovina, United States
  • St Joseph Heritage HealthcareFullerton, United States
  • Newport Huntington Medical GroupHuntington Beach, United States
  • Desert Medical AdvancesRancho Mirage, United States
  • Dan La, MD IncTujunga, United States
  • Wolverine Clinical TrialsTustin, United States
  • Medvin Clinical Research - SuWhittier, United States
  • Denver Arthritis ClinicDenver, United States
  • Tekton Research - Fort Collins - East Harmony RoadFort Collins, United States
  • HARAC Research CorpAvon Park, United States
  • Encore Medical Research of Boynton BeachBoynton Beach, United States
  • Clinical Research of West Florida, Inc. (Clearwater)Clearwater, United States
  • Suncoast Clinical Research, Inc.New Port Richey, United States
  • Baycare Medical GroupSt. Petersburg, United States
  • West Broward Rheumatology AssociatesTamarac, United States
  • Clinical Research of West FloridaTampa, United States
  • ForCare Clinical ResearchTampa, United States
  • Baycare Medical GroupTampa, United States
  • Great Lakes Clinical Trials - RavenswoodChicago, United States
  • Hinsdale Orthopaedics - llinois Bone & Joint InstituteHinsdale, United States

And 106 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2022-501425-20-00
  • J1A-MC-KDAF
  • U1111-1283-9566
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (7)