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

• Register: ClinicalTrials.gov
• Last refreshed on: 3 October 2023
• Main ID: NCT02760407
• Date of registration: 29/04/2016
• Prospective Registration: Yes
• Primary sponsor: R-Pharm International, LLC
• Public title: 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 CREDO 2
• Scientific title: 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
• Date of first enrolment: June 6, 2016
• Target sample size: 1648
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02760407
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Bulgaria, China, Colombia, Czech Republic, Czechia, Estonia, Germany, Hungary, Korea, Republic of, Latvia, Lithuania, Mexico, Poland, Romania, Russian Federation, Taiwan, United Kingdom, United States

Contacts

• Name: Mikhail Samsonov
• Affiliation: R-Pharm

Key inclusion & exclusion criteria

Inclusion 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. (If the
subject was diagnosed according to ACR 1987 criteria previously, the Investigator may
classify the subject per ACR 2010 retrospectively, using available source data)

- Inadequate response to treatment with oral, SC, or intramuscular MTX (defined as a
subject with at least 12 weeks of exposure prior to Screening and with either absence
of any documented clinically significant response, or documented initial clinical
response with subsequent loss of that response or partial response) 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 route of administering MTX had to have been stable for
at least 6 weeks prior to Screening. A lower dose of MTX (=7.5 mg/week) was permitted
for subjects enrolled in the Republic of Korea, consistent with local clinical
practice.

- 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 the normal range (ULN) at Screening based on the central laboratory
results.

Exclusion Criteria:

- Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (eg, 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 are 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

- 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 should not 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):

1. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine,
chloroquine, gold, penicillamine, minocycline, or doxycycline

2. 12 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

3. 24 weeks for cyclophosphamide

- Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination
with live vaccines during the study

- Participation in any other investigational drug study within 30 days or 5 times the
terminal half-life of the investigational drug, whichever is longer, prior to baseline

- Other treatments for RA (e.g., Prosorba Device/Column) within 6 months prior to
baseline

- Use of intra-articular hyaluronic acid injections within 4 weeks prior to baseline

- Use of non-steroidal anti-inflammatory drugs (NSAIDs) on unstable dose or switching of
NSAIDs within 2 weeks prior to baseline

- Previous participation in this study (randomized) or another study of OKZ

- Subjects with concurrent acute or chronic viral hepatitis B or C infection as detected
by blood tests at Screening(e.g., positive for hepatitis B surface antigen [HBsAg],
total hepatitis B core antibody [anti-HBc], or hepatitis C virus antibody [HCV Ab]).
Subjects who are are positive for hepatitis B surface antibodies (anti-HBs), but
negative for HBsAg and anti-HBc, will be eligible

- Subjects with human immunodeficiency virus (HIV) infection

- Subjects with:

1. Suspected or confirmed current active TB disease or a history of active TB
disease

2. Close contact (i.e., sharing the same household or other enclosed environment,
such as a social gathering place, workplace, or facility, for extended periods
during the day) with an individual with active TB within 1.5 years prior to
Screening

- Concurrent malignancy or a history of malignancy within the last 5 years (with the
exception of successfully treated carcinoma of the cervix in situ and successfully
treated basal cell carcinoma and squamous cell carcinoma not less than 1 year prior to
Screening [and no more than 3 excised skin cancers within the last 5 years prior to
Screening])

- Subjects with any infection requiring oral antibiotic or antiviral therapy in the 2
weeks prior to Screening or at baseline, injectable anti-infective therapy in the last
4 weeks prior to baseline, or serious or recurrent infection with history of
hospitalization in the 6 months prior to baseline

- Subjects with evidence of disseminated herpes zoster infection, zoster encephalitis,
meningitis, or other non-self-limited herpes zoster infections in the 6 months prior
to baseline

- Subjects with planned surgery during the study or surgery = 4 weeks prior to Screening
and from which the subject has not fully recovered, as judged by the Investigator

- Subjects with diverticulitis or other symptomatic GI conditions that might predispose
the subject to perforations, including subjects with history of such predisposing
conditions (e.g., diverticulitis, GI perforation, or ulcerative colitis)

- Pre-existing central nervous system demyelinating disorders (e.g., multiple sclerosis
and optic neuri


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Olokizumab 64mg q4w

Drug: Adalimumab 40mg q2w

Drug: Placebo q2w

Drug: Olokizumab 64mg q2w

Primary Outcome(s)

Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response [Time Frame: at Week 12]

Secondary Outcome(s)

Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response [Time Frame: at Week 24]

Percentage of Subjects With Clinical Disease Activity Index (CDAI) = 2.8 (Remission) [Time Frame: at Week 24]

Percentage of Subjects Achieving Low Disease Activity: Olokizumab Comparison With Adalimumab [Time Frame: at Week 12]

Percentage of Subjects Achieving Low Disease Activity [Time Frame: at Week 12]

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

Percentage of Subjects Achieving ACR20 Response: Olokizumab Comparison With Adalimumab [Time Frame: at Week 12]

Secondary ID(s)

CL04041023

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Quintiles, Inc.

OCT Clinical Trials

Results

• Results available: Yes
• Date Posted: 30/04/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02760407