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

NCT02760368 | Completed Phase 3 Results DMC

• 2 other identifiers: CL040410222014-004719-36
• Study Type: interventional
• Target: 428
• Locations: 3 countries
• Sites: 40

Brief 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.

Conditions

Rheumatoid Arthritis

Keywords

moderate Rheumatoid Arthritis; severe Rheumatoid Arthritis; subcutaneous; Olokizumab

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response

  A responder was defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. The calculations were based on a ≥ 20% improvement from baseline in the swollen joint count (SJC) assessed in 66 joints and in the tender joint count (TJC) assessed in 68 joints; and a ≥ 20% improvement from baseline in at least 3 of the 5 remaining core set measures: Patient Global Assessment of Disease Activity (Visual Analog Scale (VAS) assessment), Patient Assessment of Pain (VAS assessment), Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician Global Assessment (VAS assessment), Level of acute phase reactant (CRP or ESR, using level of CRP in this study).

  at Week 12

Secondary Outcomes (4)

• Percentage of Subjects Achieving Low Disease Activity

  at Week 12

• Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire Disability Index (HAQ-DI)

  Baseline to Week 12

• Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response

  at Week 24

• Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 (Remission)

  at Week 24

Study Arms (3)

Arm 1: Olokizumab q4w

EXPERIMENTAL

Olokizumab 64 mg Subcutaneous q4w +placebo+ Methotrexate (oral) in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.)

Drug: Olokizumab; Drug: Placebo

Arm 2: Olokizumab q2w

EXPERIMENTAL

Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral)

Drug: Olokizumab

Arm 3: Placebo

PLACEBO COMPARATOR

Placebo Subcutaneous q2w + Methotrexate (oral)

Drug: Placebo

Interventions

Olokizumab DRUG

160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial

Arm 1: Olokizumab q4w; Arm 2: Olokizumab q2w

Placebo DRUG

sodium chloride 0.9% solution supplied in polypropylene plastic ampoules of 10 mL cartons to contain 10 ampoules

Arm 1: Olokizumab q4w; Arm 3: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects may be enrolled in the study only if they meet all of the following criteria:
• Subjects willing and able to sign informed consent
• Subjects must have a diagnosis of adult onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 12 weeks prior to Screening.
• Inadequate response to treatment with MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if intolerant to higher doses).
• The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening.
• Subjects must be willing to take folic acid or equivalent throughout the study
• Subjects must have moderately to severely active RA disease as defined by all of the following:
• ≥6 tender joints (68 joint count) at Screening and baseline; and
• ≥6 swollen joints (66 joint count) at Screening and baseline; and
• CRP above ULN at Screening based on the central laboratory results.

You may not qualify if:

• Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus). However, subjects could have secondary Sjogren's syndrome or hypothyroidism
• Subjects who were Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)
• Prior exposure to any licensed or investigational compound directly or indirectly targeting IL-6 or IL-6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase \[SYK\] inhibitors)
• Prior treatment with cell-depleting therapies, including anti-CD20 or investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, and anti-CD19)
• Prior use of bDMARDs, with the following exception:
• weeks for etanercept
• weeks for infliximab
• weeks for adalimumab, certolizumab, and golimumab
• Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to baseline
• Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent), or change in dosage within 2 weeks prior to baseline
• Prior documented history of no response to hydroxychloroquine and sulfasalazine
• Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs were not to be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA):
• weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline
• weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to baseline: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at a dosage of 50 grams 4 times daily for at least 24 hours
• weeks for cyclophosphamide

Sponsors & Collaborators

• R-Pharm International, LLC: lead
• Quintiles, Inc.: collaborator
• OCT Clinical Trials: collaborator
• Mene Research: collaborator

Study Sites (40)

City Clinical Hospital #1

Minsk, 220013, Belarus

Location

Vitebsk Regional Clinical Hospital

Vitebsk, 210037, Belarus

Location

DCC 'Sv. Pantaleymon' OOD

Pleven, 5800, Bulgaria

Location

UMHAT "Kaspela", EOOD

Plovdiv, 4002, Bulgaria

Location

UMHAT "Sv. Ivan Rilski", EAD

Sofia, 1431, Bulgaria

Location

MC "Synexus - Sofia", EOOD

Sofia, 1784, Bulgaria

Location

Regional State Budgetary Healthcare Institution "Barnaul City Hospital #4"

Barnaul, Altayskiy Kray, 656050, Russia

Location

SAHI of Kemerovo region "Regional Clinical Hospital for War Veterans"

Kemerovo, Kemerovo Oblast, 650000, Russia

Location

Medical Center LLC "Maksimum Zdoroviya"

Kemerovo, Kemerovo Oblast, 650066, Russia

Location

Budgetary Healthcare Institution "Kursk Regional Clinical Hospital" of Healthcare Committee of Kursk region

Kursk, Kursk Oblast, 305007, Russia

Location

SPb SBHI "Clinical Rheumatological Hospital #25", Fourth Rheumatology Unit

Saint Petersburg, Leningradskaya Oblast', 190068, Russia

Location

FSBEI HE "First Moscow State Medical University n.a. I.M. Sechenov of MoH of Russian Federation", UCH #1

Moscow, Moscovskaya Oblast, 119435, Russia

Location

FSBEI HE "FMSMU n.a. I.M. Sechenov of MoH of RF", University Hospital #2, Departament of New Drugs Introduction

Moscow, Moscovskaya Oblast, 119435, Russia

Location

SBEI HPE "First Moscow State Medical University n.a. I.M. Sechenov of MoH of Russian Federation" UCH #3

Moscow, Moscovskaya Oblast, 119435, Russia

Location

State Budgetary Healthcare Institution of Moscow "City Clinical Hospital #1 n.a. Pirogov" Healthcare Departament of Moscow

Moscow, Moscovskaya Oblast, 19049, Russia

Location

State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department

Moscow, Moscow Oblast, 111539, Russia

Location

SBHI of Moscow "City Clinical Hospital #4 of Moscow Healthcare Departament"

Moscow, Moscow Oblast, 115093, Russia

Location

SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko"

Nizhny Novgorod, Nizhny Novgorod Oblast, 603126, Russia

Location

State Autonomous Healthcare Institution of Novosibirsk region "City Polyclinic #1"

Novosibirsk, Novosibirsk Oblast, 630099, Russia

Location

LLC "Clinical Diagnostic Center "Ultramed"

Omsk, Omsk Oblast, 644024, Russia

Location

Budgetary Healthcare Institution of Omsk Region "Regional Clinical Hospital"

Omsk, Omsk Oblast, 644111, Russia

Location

SBHI of the Republic of Karelia "Republican Hospital named after V.A. Baranov"

Petrozavodsk, Republic of Karelia, 185019, Russia

Location

State Budgetary Healthcare Institution "Republican Clinical Hospital n.a. G.G. Kuvatov"

Ufa, Respublic of Bashkortostan, 450005, Russia

Location

SBEI HPE "Rostov State Medical University" of Ministry of Health of the Russian Federation

Rostov-on-Don, Rostov Oblast, 344022, Russia

Location

State Healthcare Institution "Regional Clinical Hospital"

Saratov, Saratov Oblast, 410053, Russia

Location

SBEI HPE "SSMU n.a. V.I. Razumovsky of MoH of RF", Clinical Hospital n.a. S.R. Mirotvorcev, Therapeutic Departament

Saratov, Saratov Oblast, 410054, Russia

Location

Non-governmental Healtheare Institution "Regional Clinical Hospital at Smolensk station of OJSC "Russian Railways"

Smolensk, Smolensk Oblast, 214025, Russia

Location

SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"

Stavropol, Stavropol Kray, 355030, Russia

Location

State Budgetary Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital #1"

Yekaterinburg, Sverdlovsk Oblast, 620102, Russia

Location

SBEI HPE "Ural State Medical University" of MoH of RF based MBI "Central City Clinical Hospital #6"

Yekaterinburg, Sverdlovsk Oblast, 620149, Russia

Location

State Autonomous Healthcare Institution "Republican Clinical Hospital of Ministry of Health of Tatarstan Republic

Kazan', The Republic of Tatarstan, 420064, Russia

Location

State Healthcare Institution of Tula region "Tula Regional Clinical Hospital"

Tula, Tulskaya Oblast, 300053, Russia

Location

State Healthcare Institution "Ulyanovsk Regional Clinical Hospital"

Ulyanovsk, Ulyanovsk Oblast, 432063, Russia

Location

SBHI of Vladimir Region "Regional Clinical Hospital", Rheumatology Departament

Vladimir, Vladimirskaya Oblast’, 600023, Russia

Location

SBHI "Yaroslavl Regional Clinical Hospital", Rheumatology department

Yaroslavl, Yaroslavl Oblast, 150062, Russia

Location

State Autonomous Helthcare Institution of Yaroslavl region "Clinical Hospital of Emergency Care n.a. Solovyev"

Yaroslavl, Yaroslavsakaya Oblast, 150003, Russia

Location

FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"

Moscow, 115522, Russia

Location

City Clinical Hospital №5 of Nizhny Novgorod

Nizhny Novgorod, 603005, Russia

Location

Ryazan State Medical University n.a. I.P. Pavlov based on Regional Clinical Cardiology Dispensary

Ryazan, 390026, Russia

Location

SBHI "North-West Federat Medical Research Center n.a. V.A.Almazov" of the Ministry of Healthcare of the Russian Federation

Saint Petersburg, 197341, Russia

Location

Related Publications (1)

• Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, Maslyanskiy AL, Samsonov M, Stoilov R, Zonova EV, Genovese M. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3.

  PMID: 34344706 DERIVED

Related Links

• Nasonov E, Fatenejad S, Korneva E, Krechikova D. - Safety and Efficacy of Olokizumab in a Phase III Trial of Patients with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate - CREDO1 Study \[abstract\].
• E. Nasonov, R. Stoilov, T. Tyabut, M. C. Genovese. 2020 OP0021 Olokizumab, Monoclonal Antibody Against IL6, in Patients with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate:Results of Phase III CREDO-1 study
• E. Nasonov, M. Ivanova, M. Samsonov, T. Tyabut, M. C. Genovese; 2020 THU0176 Olokizumab Improves Patient Reported Outcomes in Patients with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate: Results CREDO-1 study

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

olokizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Maria Lemak, Scientific Advisor
• Organization: R-Pharm

lemak@rpharm.ru

0074959567937

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2016
• First Posted: May 3, 2016
• Study Start: May 19, 2016
• Primary Completion: August 1, 2018
• Study Completion: October 1, 2018
• Last Updated: September 21, 2023
• Results First Posted: October 30, 2020

Record last verified: 2023-09

Locations

BE (2); RU (34); BU (4)