NCT02760368

Evaluation of the Effectiveness and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 428 (actual)
• Sponsor: R-Pharm International, LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to determine how effective and safe the study drug Olokizumab was in patients with Rheumatoid Arthritis (RA) who had been already receiving, but not fully responding to treatment with methotrexate (MTX). The primary objective of this study was to evaluate the efficacy of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) relative to placebo in subjects with moderately to severely active rheumatoid arthritis (RA) inadequately controlled by methotrexate (MTX) therapy.

Detailed description

The goal of this Phase III study was to assess the efficacy, tolerability, and safety of OKZ in subjects with moderately to severely active RA who had responded inadequately to MTX. The primary endpoint of the trial was at Week 12. Olokizumab was expected to reduce the disease activity and improve physical function. The study was expected to provide safety information in a large group of subjects over at least a 24 week period. The CREDO 1 study included a 4-week Screening Period, a double-blind Treatment Period from Week 0 to Week 24, and a Safety Follow-Up Period from Week 24 to Week 44. At randomization, a total of 428 eligible subjects were randomly assigned to 1 of 3 treatment groups in a 1:1:1 ratio: 1. OKZ 64 mg q4w: SC injection of OKZ 64 mg q4w (alternating with SC injection of placebo OKZ q4w to maintain blinding) + MTX. 2. OKZ 64 mg q2w: SC injection of OKZ 64 mg q2w + MTX. 3. Placebo: SC injection of placebo q2w + MTX Throughout the double-blind Treatment Period, all subjects were required to remain on a stable dose of background MTX at 15 to 25 mg/week (or ≥ 10 mg/week if there was documented intolerance to higher doses) with a stable route of administration, and concomitant treatment with folic acid ≥5 mg per week or equivalent is required for all subjects. The last dose of study treatment (OKZ or placebo) was at Week 22 in all groups. Following Visit 2 (randomization), subjects returned to the study site at least every other week through Week 24 for response and safety assessments as per the study Schedule of Events. Subjects were classified in terms of their response to study treatment at Week 14, with non-responders defined as subjects in any treatment group who had not improved by at least 20% in both swollen and tender joint counts (66-68 joint assessment). Starting at or as close as possible to Week 14, non-responders were administered sulfasalazine and/or hydroxychloroquine as rescue medication in addition to the assigned treatment. After completion of the 24-week double-blind Treatment Period, subjects either rolled over into the long-term open-label extension (OLE) study or entered the Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for visits +4, +8, and +22 weeks after the last dose of study treatment. Subjects who discontinued the randomized treatment prematurely were required to come for the End of Treatment (EoT) Visit 2 weeks after the last study treatment administration and then continued with the scheduled study visits as per the Schedule of Events. The study was conducted at approximately 50 sites across 4 countries globally, which included Russia, Belarus, Turkey, and Bulgaria.

Conditions

• Rheumatoid Arthritis

Interventions

Type	Name	Description
DRUG	Olokizumab	160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
DRUG	Placebo	sodium chloride 0.9% solution supplied in polypropylene plastic ampoules of 10 mL cartons to contain 10 ampoules

Timeline

• Start date: 2016-05-19
• Primary completion: 2018-08-01
• Completion: 2018-10-01
• First posted: 2016-05-03
• Last updated: 2023-09-21
• Results posted: 2020-10-30

Locations

40 sites across 3 countries: Belarus, Bulgaria, Russia