Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Were Taking an Existing Medication Called a Tumour Necrosis Factor Alpha Inhibitor But Had Active Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 3 October 2023
• Main ID: NCT02760433
• 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, in Subjects With Rheumatoid Arthritis (RA) Who Were Taking an Existing Medication Called a Tumour Necrosis Factor Alpha Inhibitor But Had Active Disease CREDO 3
• Scientific title: 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 Tumor Necrosis Factor Alpha (TNF-a) Inhibitor Therapy
• Date of first enrolment: January 25, 2017
• Target sample size: 368
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02760433
• 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, Colombia, Czech Republic, Czechia, Germany, Hungary, Korea, Republic of, Mexico, Poland, Russian Federation, Turkey, United States

Contacts

• Name: Mikhail Samsonov
• Affiliation: R-Pharm

Key inclusion & exclusion criteria

Inclusion Criteria:

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 24 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.)

- Treatment with oral, SC, or intramuscular (IM) MTX for at least 12 weeks prior to
Screening at a dose of 15 to 25 mg/week (or =10 mg/week if there is documented
intolerance 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

- C-reactive protein (CRP) above Upper limit of normal (ULN) at Screening based on
the central laboratory results.

- Subjects must have a documented inadequate response to treatment (i.e., TNFi failure)
with =1 licensed TNFi following at least 12 weeks of therapy with that agent.
Inadequate response to treatment is classified as either:

- Primary failure: The absence of any documented clinically significant response;
or

- Secondary failure: Documented initial response with subsequent loss of that
response or partial response

Exclusion Criteria:

- 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 may 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 Interleukin (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) with the exception
of rituximab, which is allowed if it was discontinued at least 24 weeks prior to
baseline (rituximab 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).

- Prior use of bDMARDs, within the following windows prior to baseline (bDMARDs 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 etanercept and anakinra

2. 8 weeks for infliximab

3. 10 weeks for adalimumab, certolizumab, and golimumab

4. 12 weeks for abatacept

- 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])

a) subjects who are positive for hepatitis B surface antibodies (anti-HBs), but
negative for HBsAg and anti-HBc, will be eligible.

- Subjects with HIV infection

- Subjects with:

1. Suspected or confirmed current active tuberculosis (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 ther


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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Placebo

Drug: Olokizumab

Primary Outcome(s)

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

Secondary Outcome(s)

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 American College of Rheumatology 50% (ACR50) Response [Time Frame: at Week 12]

Percentage of Subjects With Clinical Disease Activity Index (CDAI) = 2.8 (Remission) [Time Frame: at Week 12]

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

Secondary ID(s)

2015-005308-27

CL04041025

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Quintiles, Inc.

OCT Clinical Trials

Mene Research

Results

• Results available: Yes
• Date Posted: 21/07/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02760433