NCT02760407

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

A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-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: 1,648 (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 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 RA inadequately controlled by MTX therapy. The secondary objective was to evaluate the efficacy of OKZ relative to adalimumab in subjects with moderately to severely active RA inadequately controlled by MTX therapy.

Detailed description

The goal of this Phase III study was to assess the efficacy, safety and tolerability 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. This 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. Subjects were assessed for eligibility to enter the study during the 4-week Screening Period. A total of 1575 subjects were planned to be randomly assigned to 1 of 4 treatment groups in a 2:2:2:1 ratio (450, 450, 450, and 225 subjects per group, respectively): 1. Olokizumab 64 mg q4w: SC injection of OKZ 64 mg q4w (alternating with SC injection of placebo q4w to maintain blinding) + MTX 2. Olokizumab 64 mg q2w: SC injection of OKZ 64 mg q2w + MTX 3. Adalimumab 40 mg q2w: SC injection of adalimumab 40 mg q2w + MTX 4. 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 with a stable route of administration. Concomitant treatment with folic acid was required for all subjects. The last dose of study treatment (OKZ, adalimumab, or placebo) was at Week 22 in all groups. Following Visit 2 (randomization; Week 0), subjects returned to the study site at least every 2 weeks through Week 24 for response and safety assessments. At Week 14, subjects who had not improved by at least 20% in both swollen and tender joint counts were classified as nonresponders and 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 had discontinued randomized treatment prematurely were required to come for the End of Treatment (EoT) Visit 2 weeks after the last study treatment administration and then continue with the scheduled study visits. Adverse events (AEs) were assessed throughout the study (starting when the subject signed the informed consent form) and evaluated using the Common Terminology Criteria for Adverse Events Version 4.0. There was ongoing monitoring of safety events, including laboratory findings, by the Sponsor or the Sponsor's designee. In addition, safety was assessed throughout the study by an independent Data Safety Monitoring Board and potential major adverse cardiac events were evaluated by an independent Cardiovascular Adjudication Committee. The study was conducted at 208 sites across 18 countries globally (in US, European Union (EU),United Kingdom (UK), Russian Federation, Asia, Latin America).

Conditions

• Rheumatoid Arthritis

Interventions

Type	Name	Description
DRUG	Olokizumab 64mg q4w	160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
DRUG	Olokizumab 64mg q2w	160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
DRUG	Adalimumab 40mg q2w	0.4 or 0.8 mL prefilled, single-dose syringe
DRUG	Placebo q2w	sodium chloride 0.9% solution supplied in either a 10 mL vial or ampoule, depending on market availability. Each placebo will be packed into a cardboard carton to contain 1 vial or ampoule

Timeline

• Start date: 2016-06-06
• Primary completion: 2019-08-02
• Completion: 2019-11-05
• First posted: 2016-05-03
• Last updated: 2023-09-21
• Results posted: 2021-04-30

Locations

203 sites across 18 countries: United States, Argentina, Brazil, Bulgaria, Colombia, Czechia, Estonia, Germany, Hungary, Latvia, Lithuania, Mexico, Poland, Romania, Russia, South Korea, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study