A Golimumab Phase 3b, Multicenter, Assessment of Intravenous Efficacy in Rheumatoid Arthritis Subjects Who Have Diminished Disease Control Despite Treatment With Infliximab (REMICADE®) (REGAIN)

This is a Phase 3b, multicenter study of the efficacy of golimumab 2 mg/kg IV in subjects with active rheumatoid arthritis who are receiving methotrexate and have inadequate disease control (defined as an erythrocyte sedimentation rate [ESR]-based Disease Activity Score in 28 joints [DAS28] ≥ 3.2 and ≥ 4 swollen and ≥ 4 tender joints) despite current anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks.

To be eligible for participation, subjects must have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, who have since exhibited a diminished response despite continued treatment. It is estimated that 200 subjects will be enrolled in the study at approximately 85 global sites.

Study Overview

• Status: Terminated
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Biological: Golimumab 2 mg/kg IV

Detailed Description

The study employs an open-label "active switch" design that moves subjects from infliximab to golimumab 2 mg/kg IV. In general, subjects eligible for the study include men or women who are currently receiving infliximab in actual clinical practice who are at least 18 years of age with active rheumatoid arthritis, and have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, but now exhibit a diminished response and inadequate disease control despite continued treatment. Subjects must have received infliximab in combination with methotrexate for a minimum of 9 months prior to the first screening visit.

The screening visit will occur sometime between Week -12 and Week -10. Consenting subjects who meet screening criteria will receive their final dose of infliximab at Week -8 as part of actual clinical practice. Golimumab IV treatment, which will be supplied by the sponsor, will be received at Weeks 0, 4, 12, 20, and 28. The primary endpoint is at Week 24, the final efficacy assessment is at Week 32, and a follow-up safety assessment by telephone is at Week 44. There will be a maximum of 36 weeks between the last infliximab infusion at Week -8 and the last infusion of golimumab at Week 28. The duration of study participation is expected to be a maximum of 56 weeks (including the Screening Period, 32 weeks of golimumab treatment and assessment, and a 12-week safety follow-up).

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Rimouski, Canada
  • British Columbia
    • Victoria, British Columbia, Canada
  • Newfoundland and Labrador
    • Saint-John'S, Newfoundland and Labrador, Canada
    • St. John'S, Newfoundland and Labrador, Canada
  • Ontario
    • Hamilton, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Huntsville, Alabama, United States
  • Arizona
    • Peoria, Arizona, United States
    • Phoenix, Arizona, United States
  • Arkansas
    • Fort Smith, Arkansas, United States
  • California
    • Fremont, California, United States
    • Fullerton, California, United States
    • Long Beach, California, United States
    • Santa Maria, California, United States
    • Thousand Oaks, California, United States
    • Whittier, California, United States
  • Connecticut
    • Bridgeport, Connecticut, United States
  • Florida
    • Clearwater, Florida, United States
    • Miami, Florida, United States
    • Orlando, Florida, United States
    • Sarasota, Florida, United States
    • Tampa, Florida, United States
  • Idaho
    • Coeur D'Alene, Idaho, United States
  • Indiana
    • Indianapolis, Indiana, United States
    • South Bend, Indiana, United States
  • Minnesota
    • Eagan, Minnesota, United States
    • Edina, Minnesota, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • New York
    • Orchard Park, New York, United States
  • North Carolina
    • Asheville, North Carolina, United States
    • Charlotte, North Carolina, United States
    • Greensboro, North Carolina, United States
    • Hickory, North Carolina, United States
    • Wilmington, North Carolina, United States
  • Ohio
    • Dayton, Ohio, United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
    • Philadelphia, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
    • Wyomissing, Pennsylvania, United States
  • South Carolina
    • Charleston, South Carolina, United States
    • Columbia, South Carolina, United States
    • Myrtle Beach, South Carolina, United States
  • Tennessee
    • Hixson, Tennessee, United States
    • Jakson, Tennessee, United States
    • Nashville, Tennessee, United States
  • Texas
    • Houston, Texas, United States
    • Plano, Texas, United States
    • San Antonio, Texas, United States
  • Virginia
    • Arlington, Virginia, United States
  • Washington
    • Spokane, Washington, United States
  • Wisconsin
    • Glendale, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Major Inclusion Criteria include (but not limited to):

• Have a diagnosis of Rheumatoid Arthritis (according to the revised 1987 criteria of the American Rheumatism Association).
• Treatment with infliximab and methotrexate for >= 9 months, (with stable doses of methotrexate over last 16 weeks of 7.5 mg/week to 25 mg/week) and (anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks).
• Disease Activity Score 28 (DAS28) ≥ 3.2 based on Erythrocyte Sedimentation Rate (ESR) at Week -8 and Week 0.
• Swollen joint count (SJC) ≥ 4 and tender joint count (TJC) ≥ 4 at Week - 8 and at Week 0.
• Prior response confirmed by physician.

Major Exclusion Criteria include (but not limited to):

• Have a history of latent or active granulomatous infection, including histoplasmosis, or Have a history of latent or active granulomatous infection, including histoplasmosis, or coccidioidomycosis, prior to the first screening visit or during the Screening Period.
• Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
• Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis.
• Have previously received more than 1 of the currently approved subcutaneous (SC) administered anti-TNFα agents, etanercept, certolizumab pegol, golimumab, or adalimumab.
• Are pregnant, nursing, or planning a pregnancy or fathering a child within 6 months after receiving the last administration of the study agent.
• Weight less than 35 kg or greater than 110 kg (less than 77 pounds or greater than 242 pounds).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Golimumab 2 mg/kg IV; Study drug (golimumab 2 mg/kg IV) will be administered as an intravenous (IV) infusion at Weeks 0, 4, 12, 20 and 28.	Biological: Golimumab 2 mg/kg IV; Study drug (golimumab 2 mg/kg IV) will be administered as an intravenous (IV) infusion at Weeks 0, 4, 12, 20 and 28.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 24	The ACR 20 Response is defined as greater than or equal to (>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and erythrocyte sedimentation rate (ESR).	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved an ACR 20 Response at Week 24 With Confirmed Presence of Antibodies to Infliximab	The ACR 20 Response is defined as >= 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (010 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and ESR.	Week 24
Percentage of Participants Who Acheived ACR 20 Response at Week 24 With Trough Infliximab Levels Below the Lower Limit of Quantification (LLOQ)	The ACR 20 Response is defined as >= 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (010 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and ESR.	Week 24

Collaborators and Investigators

• Sponsor: Janssen Biotech, Inc.

Publications and helpful links

Helpful Links

• A Golimumab Phase 3b, Multicenter, Assessment of Intravenous Efficacy in Rheumatoid Arthritis Subjects Who Have Diminished Disease Control Despite Treatment with Infliximab (REMICADE ®) REGAIN

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 11, 2013
• First Submitted That Met QC Criteria: October 11, 2013
• First Posted (Estimate): October 16, 2013

Study Record Updates

• Last Update Posted (Actual): April 12, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Arthritis, Rheumatoid
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Golimumab
• Other Study ID Numbers: CR102117; CNTO148ART3003 (Other Identifier: Janssen Biotech, Inc.); 2013-001809-91 (EudraCT Number)