Re³ (Re-Cube: Retain Remicade® Response)(Study P04249AM3) (Re³)

Randomised Controlled Trial Evaluating Strategies to Optimize Disease Activity Control in RA Patients Treated With Infliximab in Clinical Practice.

This Phase IIIb, randomized, multi-national, multi-center, blinded study of Infliximab (IFX) in subjects aged 18 and older with active RA is being conducted to assess whether increasing either the infusion dose or infusion frequency in patients presenting with a disease flare after an initial response to infliximab results in a significant improvement in disease activity.

Subjects responding to an initial infliximab treatment regimen, who flare during continuation of treatment at 3 mg/kg administered every 8 weeks, will be randomly assigned to one of 3 different dosing regimens of infliximab and will be treated for 4 or 5 consecutive infusions for a total duration of 24 weeks. The infliximab control group and the infliximab increased dose group are evaluator and subject-blinded. The increased frequency group is not blinded. Clinical assessments of disease activity will be based the European League Against Rheumatism (EULAR) criteria for response. Safety parameters will be assessed at every infusion.

A disease flare is defined by an increase in DAS28 with 0.6 or more at screening, when compared to the DAS28 score measured immediately prior to the last Remicade® infusion and depends upon the actual score as well. Since prior to enrollment, the subject received Remicade® as per routine clinical practice, the days on which infusions were administered and assessments are done during the induction period do not have to be exactly at Week 2, 6 and 14.

• Drug: Infliximab Control (double-blinded)
• Drug: Infliximab Increased Dose (double-blinded)
• Drug: Infliximab Increased Frequency (open-label)

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Infliximab Increased Frequency; Drug: Infliximab Increased Dose; Drug: Infliximab Control

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• aged 18 years or more
• with RA according to ACR criteria
• presented with a disease flare after initial response to infliximab, with both response and flare being defined using the DAS28 score (EULAR criteria)
• received the standard Remicade® dosing schedule per the EU label (3 mg/kg at Weeks 0, 2, 6, [and 14])
• an initial response documented by moderate or good DAS28 improvement (EULAR criteria) from Week 0 to Week 6 or 14.

Exclusion Criteria:

• a female who is, or intends to become, pregnant during or within 6 months of the end of the study, is nursing or not using adequate contraceptive measures
• has not observed the designated periods for concomitant medications
• used any investigational medical product within 30 days prior to Baseline
• any clinically significant deviation from normal in the physical examination or chest X-ray that in the investigator's judgment, may interfere with the study evaluation or affect subject safety
• rheumatic disease other than RA or has any systemic inflammatory condition with signs and symptoms that might confound the evaluations of safety and toxicity
• allergic reaction/sensitivity to the study drug or its excipients that requires corticosteroid pre-infusion medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Increased Frequency; Continuing the same dose of 3 mg/kg infliximab, but at every 6 weeks	Drug: Infliximab Increased Frequency; Continuing the same dose of 3 mg/kg infliximab, but at every 6 weeks for 24 weeks; Other Names: Increased Frequency
Experimental: Increased Dose; 3 mg/kg infliximab + 1 extra vial (100 mg) infliximab, every 8 weeks	Drug: Infliximab Increased Dose; 3 mg/kg infliximab + 1 extra vial (100 mg) infliximab every 8 weeks for 24 weeks; Other Names: Increased Dose
Active Comparator: Control; Continuation of infliximab 3 mg/kg every 8 weeks	Drug: Infliximab Control; Continuation of infliximab 3 mg/kg every 8 weeks for 24 weeks; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Disease Activity Score Based on 28 Joint Count (DAS28) Score.	Descriptive summary of DAS28 (Disease Activity Score Based on 28 Joint Count)change from Baseline to the end of study (Week 24) in the population with available data at both Baseline and Week 24 (increased dose group, n=5; increased frequency group, n=7; and control group, n=5). DAS28 is a unit scale from 2.0 (best value) to 10.0 (worst value).	Between Screening (Week <=1) and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Integrated Therapeutics Group

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: October 31, 2006
• First Submitted That Met QC Criteria: October 31, 2006
• First Posted (Estimate): November 1, 2006

Study Record Updates

• Last Update Posted (Actual): April 11, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: P04249

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php