Study of the Efficacy and Safety of Olokizumab in Patients with Moderately to Severely Active Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 26 October 2021
• Main ID: EUCTR2015-005309-35-HU
• Date of registration: 02/02/2017
• Prospective Registration: Yes
• Primary sponsor: R-Pharm
• Public title: Study of the Efficacy and Safety of Olokizumab in Patients with Moderately to Severely Active Rheumatoid Arthritis
• Scientific title: A Multicenter, Open-Label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects with Moderately to Severely Active Rheumatoid Arthritis - Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO) 4
• Date of first enrolment: 16/03/2017
• Target sample size: 1880
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005309-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Medical Department
• Affiliation: JSC R-Pharm

• Name: Medical Department
• Affiliation: JSC R-Pharm

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject must be willing and able to sign informed consent
2. Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025).
3. Subject must have maintained their stable dose (and route) of MTX 15 to 25 mg/week (or =10 mg/week if there is documented intolerance to higher doses) during the core study and plan to maintain the same dose and route of administration for =12 additional weeks.
4.Subjects must be willing to take folic acid or equivalent throughout the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1576
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 304

Exclusion criteria:
1. Subject with any medically important condition in the core study (e.g., clinically significant laboratory values, frequent AEs or SAEs, infection SAEs, and/or other concurrent severe and/or uncontrolled medical condition) which would make this subject unsuitable for inclusion in the OLE study in the Investigator’s judgement.
2. Subject has evidence of active TB
3. Subject with a positive or repeated indeterminate interferon-gamma release assay (IGRA) result at Week 22 of the core study
? Subjects may be enrolled in the OLE study if they fulfill all 3 of the following criteria prior to the first dose of study treatment:
a. Active TB is ruled out by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice);
b. The subject starts prophylaxis for LTBI according to country-specific/Centers for Disease Control and Prevention (CDC) guidelines (treatment with isoniazid for 6 months is not an appropriate prophylactic regime for this study and it should not be used); and
c. The subject is willing to complete the entire course of recommended LTBI therapy
4. Subject has planned surgery during the first 12 weeks of the OLE study
5. Female subjects who are pregnant or lactating, or who are planning to become pregnant during the study or within 6 months of the last dose of study treatment
6. Female subjects of childbearing potential (unless permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of natural amenorrhea as defined by the amenorrhea with underlying status [e.g., correlative age] or 6 months of natural amenorrhea with documented serum follicle-stimulating hormone levels >40 mIU/mL and estradiol <20 pg/mL) who are not willing to use a highly effective method of contraception during the study and for at least 6 months after the last administration of study treatment
OR
Male subjects with partners of childbearing potential not willing to use a highly effective method of contraception during the study and for at least 3 months after the last administration of study treatment.
7. Subject is unwilling or unable to follow the procedures outlined in the protocol
8. Other medical or psychiatric conditions, or laboratory abnormalities that may increase the potential risk associated with study participation and administration of the study treatment, or that may affect study results interpretation and, as per Investigator’s judgement, make the subject ineligible.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Moderately to Severely Active Rheumatoid Arthritis
MedDRA version: 19.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Olokizumab
Product Code: (CDP6038; L04041)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Olokizumab
Other descriptive name: CDP6038
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 160-

Primary Outcome(s)

Primary end point(s): -The nature, incidence, severity, and outcome of adverse events (AEs), including serious adverse events (SAEs) and AEs of special interest (AESIs)
-Follow-up- adjusted incidence and event rates (per 100 subject-years of follow-up) for SAEs and AESIs
-Proportions of subjects with clinically significant laboratory abnormalities
-Assessment of changes over time in clinical laboratory parameters, vital sign measurements, and physical examination findings
-Time from first exposure to OKZ to the first occurrence of any major adverse cardiac event (MACE)
-Incidence and titer of antidrug antibodies (ADAs) to OKZ, incidence of neutralizing antibodies, and the time course of antibodies

Timepoint(s) of evaluation of this end point: Various time points throughout the study - please refer to the detailed
'Schedule of Events' table in the protocol for full details.

Main Objective: The primary objective of this study is to evaluate the long-term safety and tolerability of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) in subjects with moderately to severely active rheumatoid arthritis (RA) who previously completed 24 weeks of double blind treatment in Study CL04041022, CL04041023, or CL04041025 (core studies).

Secondary Objective: • To evaluate the long-term efficacy of OKZ
• To evaluate the long-term immunogenicity of OKZ
• To evaluate the physical function and quality of life of subjects receiving long-term treatment with OKZ

Secondary Outcome(s)

Secondary end point(s): -Proportion of subjects achieving an American College of Rheumatology 20% (ACR20), American College of Rheumatology 50% (ACR50), and American College of Rheumatology 70% (ACR70) response who remain on randomized open-label treatment and in the study, assessed at all applicable time points
-Evaluating the impact of ADAs to OKZ on subject safety and efficacy
-Proportion of subjects with Simplified Disease Activity Index (SDAI) =3.3 remission, who remain on randomized open-label treatment and in the study, assessed at all applicable time points
-Proportion of subjects with Disease Activity Score 28-joint count (DAS28) low disease activity (based on DAS28 C-reactive protein [CRP] <3.2), who remain on randomized open-label treatment and in the study, assessed at all applicable time points
-Change from baseline over time in DAS28 (CRP), assessed at all applicable time points
-Change from baseline over time in the measure of physical ability based on Health Assessment Questionnaire-Disability Index (HAQ-DI), assessed at all applicable time points
-Proportion of subjects with improvement from baseline in HAQ-DI score =0.22, who remain on randomized open-label treatment and in the study, assessed at all applicable time points
-Change from baseline over time in the scores for the following patient-reported outcomes (PRO) measures, assessed at all applicable time points:
o Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) total scores
o European Quality of Life-5 Dimensions (EQ-5D)
o Work Productivity Survey-Rheumatoid Arthritis (WPS-RA)
o Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue)
-Change from baseline over time in SDAI and Clinical Disease Activity Index (CDAI), assessed at all applicable time points
-Proportion of subjects with moderate to good responses for European League Against Rheumatism (EULAR) based on DAS28 (CRP), who remain on randomized open-label treatment and in the study, assessed at all applicable time points, where a moderate response is defined as either DAS28 (CRP) =5.1 with an improvement from baseline in DAS28 (CRP) >0.6 and =1.2, or DAS28 (CRP) >3.2 with an improvement from baseline in DAS28 (CRP) >1.2, and a good response is defined as DAS28 (CRP) =3.2 with an improvement from baseline in DAS28 (CRP) >1.2
-Change from baseline to all time points in the components of the ACR response criteria

Timepoint(s) of evaluation of this end point: Various time points throughout the study - please refer to the detailed
'Schedule of Events' table in the protocol for full details.

Secondary ID(s)

CL04041024

2015-005309-35-GB

Source(s) of Monetary Support

R-Pharm

Ethics review

Status: Approved
Approval date: 08/03/2017
Contact: