Efficacy and Safety Study of ABP 501 Compared to Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT01970475
• Recruitment Status: Completed
• First Posted: October 28, 2013
• Results First Posted: December 13, 2016
• Last Update Posted: December 13, 2016
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: October 23, 2013
• First Posted Date: October 28, 2013
• Results First Submitted Date: October 20, 2016
• Results First Posted Date: December 13, 2016
• Last Update Posted Date: December 13, 2016
• Study Start Date: October 2013
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 20, 2016)

Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 24 [ Time Frame: Baseline and Week 24 ]

A participant was a responder if the following 3 criteria for improvement from Baseline were met:

• ≥ 20% improvement in tender joint count;
• ≥ 20% improvement in swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters:
  • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
  • Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
  • Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
  • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
  • C-Reactive Protein level.

Original Primary Outcome Measures (submitted: October 23, 2013)

The primary efficacy endpoint is ACR20 (20% improvement in ACR core set measurements) at week 24. [ Time Frame: Week 24 ]

20% improvement in ACR (American College of Rheumatology) core set measurements

Current Secondary Outcome Measures (submitted: October 20, 2016)

• Change From Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) [ Time Frame: Baseline and weeks 2, 4, 8, 12, 18, and 24 ]
  The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:

  • The number of swollen and tender joints assessed using the 28-joint count;
  • C-reactive protein (CRP) level
  • Patient's global assessment of disease activity assessed on a score from 0 to 100 transformed from the result measured on a horizontal scale from 0 (no RA activity at all) to 10 (worst RA activity imaginable).

  The DAS28-CRP score ranges from approximately zero to ten. Higher DAS28-CRP scores indicate higher disease activity. A repeated measures analysis with the DAS28-CRP change from baseline as the response and the stratification variables, visit, treatment, treatment-by-visit interaction and the baseline DAS28-CRP measurement as predictors in the model was performed.
• Percentage of Participants With an ACR20 Response at Week 2 and Week 8 [ Time Frame: Baseline, week 2 and week 8 ]
  A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 20% improvement in tender joint count;
  • ≥ 20% improvement in swollen joint count; and
  • ≥ 20% improvement in at least 3 of the 5 following parameters:
    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
    • Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • C-Reactive Protein level.
• Percentage of Participants With an ACR50 Response at Week 24 [ Time Frame: Baseline and week 24 ]
  A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 50% improvement in tender joint count;
  • ≥ 50% improvement in swollen joint count; and
  • ≥ 50% improvement in at least 3 of the 5 following parameters:
    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
    • Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • C-Reactive Protein level.
• Percentage of Participants With an ACR70 Response at Week 24 [ Time Frame: Baseline and Week 24 ]
  A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 70% improvement in tender joint count;
  • ≥ 70% improvement in swollen joint count; and
  • ≥ 70% improvement in at least 3 of the 5 following parameters:
    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
    • Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • C-Reactive Protein level.
• Number of Participants With Adverse Events [ Time Frame: From the time of first treatment up to 28 days following the last dose of study treatment; 26 weeks. ]
  Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 according to the following scale: 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; 5 = fatal. A treatment-related AE is defined as an event where the answer to the question "is there a reasonable possibility that the event may have been caused by the Investigational Medicinal Product" was yes. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria:

  • fatal
  • life threatening (places the subject at immediate risk of death)
  • requires inpatient hospitalization or prolongation of existing hospitalization
  • results in persistent or significant disability/incapacity
  • congenital anomaly/birth defect
  • other medically important serious event.
• Percentage of Participants Who Developed Antibodies to ABP 501 or Adalimumab [ Time Frame: Up to week 26 ]
  Two validated assays were used to detect the presence of anti-drug antibodies. Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against ABP 501 and adalimumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based bioassay to determine neutralizing activity against ABP 501 or adalimumab (Neutralizing Antibody Assay). Developing antibody incidence is defined as a negative or no antibody result at baseline and a positive antibody result at a post-baseline time point.

Original Secondary Outcome Measures (submitted: October 23, 2013)

• Disease Activity Score 28-CRP [ Time Frame: Week 24 ]
• ACR50 and ACR70 response [ Time Frame: Week 24 ]
  50% or 70% improvement in ACR core set measurements
• Incidence of anti-drug antibodies [ Time Frame: Week 26 ]
• Subject incidence of adverse events and serious adverse events [ Time Frame: Week 26 ]
• Clinically significant changes in laboratory values and vital signs [ Time Frame: Week 26 ]
• ACR20 response [ Time Frame: Weeks 2 and 8 ]
  20% improvement in ACR core set measurements

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

Descriptive Information

• Brief Title: Efficacy and Safety Study of ABP 501 Compared to Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis
• Official Title: A Randomized, Double-blind, Phase 3 Study of ABP 501 Efficacy and Safety Compared to Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis
• Brief Summary: The purpose of this study is to compare the effectiveness and safety of ABP 501 against adalimumab (HUMIRA®) in adults with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Arthritis, Rheumatoid

Intervention

• Biological: ABP 501
  Solution for subcutaneous injection in pre-filled syringe
  Other Names:

  • AMJEVITA™
  • Adalimumab-atto
• Biological: Adalimumab
  Solution for subcutaneous injection in pre-filled syringe
  Other Name: HUMIRA®

Study Arms

• Experimental: ABP 501
  Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
  Intervention: Biological: ABP 501
• Active Comparator: Adalimumab
  Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
  Intervention: Biological: Adalimumab

Publications *

• Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1.
• Cohen S, Genovese MC, Choy E, Perez-Ruiz F, Matsumoto A, Pavelka K, Pablos JL, Rizzo W, Hrycaj P, Zhang N, Shergy W, Kaur P. Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study. Ann Rheum Dis. 2017 Oct;76(10):1679-1687. doi: 10.1136/annrheumdis-2016-210459. Epub 2017 Jun 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 3, 2014): 526
• Original Estimated Enrollment (submitted: October 23, 2013): 500
• Actual Study Completion Date: November 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Men or women ≥ 18 and ≤ 80 years old
2. Subjects must be diagnosed with rheumatoid arthritis for at least 3 months before baseline
3. Active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints at screening and baseline
4. Subjects must be taking MTX for ≥ 12 consecutive weeks and on a stable dose of 7.5 to 25 mg/week for > 8 weeks prior to receiving the study drug and be willing to remain on stable dose throughout the study
5. Subject has no known history of active tuberculosis

Exclusion Criteria:

1. Class IV RA, Felty's syndrome or history of prosthetic or native joint infection
2. Major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren's syndrome
3. Prior use of 2 or more biologic therapies for RA
4. Previous receipt of HUMIRA® (adalimumab) or a biosimilar of adalimumab
5. Ongoing use of prohibited treatments

Other Inclusion/Exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, United Kingdom, United States
• Removed Location Countries: Bulgaria, Czech Republic, Hungary, Mexico, Poland, Romania, Russian Federation, Spain

Administrative Information

• NCT Number: NCT01970475
• Other Study ID Numbers: 20120262; 2013-000525-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: October 2016