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

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Arthritis, Rheumatoid	Biological: ABP 501; Biological: Adalimumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 526 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: October 2013
• Actual Primary Completion Date: November 2014
• Actual Study Completion Date: November 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: ABP 501; Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Biological: ABP 501; Solution for subcutaneous injection in pre-filled syringe; Other Names: AMJEVITA™; Adalimumab-atto
Active Comparator: Adalimumab; Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.	Biological: Adalimumab; Solution for subcutaneous injection in pre-filled syringe; Other Name: HUMIRA®

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

2. 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.
3. 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.
4. 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.
5. 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.
6. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Research Site

Victorville, California, United States, 92395

United States, Florida

Research Site

Jupiter, Florida, United States, 33458

United States, Georgia

Research Site

Sandy Springs, Georgia, United States, 30328

United States, Michigan

Research Site

Lansing, Michigan, United States, 48910

United States, Ohio

Research Site

Middleburg Heights, Ohio, United States, 44130

Canada, Manitoba

Research Site

Winnipeg, Manitoba, Canada, R3A 1M3

Germany

Research Site

Hattingen, Nordrhein-westfalen, Germany, 45525

United Kingdom

Research Site

Barnsley, England, United Kingdom, S75 2EP

Research Site

North Shields, England, United Kingdom, NE29 8NH

Research Site

Suffolk, England, United Kingdom, IP4 5PD

Research Site

Cardiff, Wales, United Kingdom, CF14 4XN

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01970475
• Other Study ID Numbers: 20120262; 2013-000525-31 ( EudraCT Number )
• First Posted: October 28, 2013
• Results First Posted: December 13, 2016
• Last Update Posted: December 13, 2016
• Last Verified: October 2016

Keywords provided by Amgen:

Arthritis; Rheumatoid

Additional relevant MeSH terms:

Adalimumab; Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Anti-Inflammatory Agents; Antirheumatic Agents