Coherus RA Study

• Register: EUCTR
• Last refreshed on: 13 June 2016
• Main ID: EUCTR2014-000443-33-HU
• Date of registration: 06/06/2014
• Prospective Registration: Yes
• Primary sponsor: Coherus Biosciences, Inc
• Public title: Coherus RA Study
• Scientific title: A Double-Blind, Randomized, Parallel-Group, Active-Control Study to Compare the Efficacy and Safety of CHS-0214 Versus Enbrel® in Subjects With Rheumatoid Arthritis and Inadequate Response to Treatment With Methotrexate (CHS-0214-02) (RApsody) - ETA 302
• Date of first enrolment: 09/09/2014
• Target sample size: 620
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000443-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes 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, France, Germany, Hungary, Israel, Italy, Japan, Poland, Russian Federation, South Africa, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Director of Regulatory Submissions
• Affiliation: Medpace UK

• Name: Director of Regulatory Submissions
• Affiliation: Medpace UK

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet the following criteria to be enrolled in Part 1 of the study:
1.Male or female adult = 18 years of age (= 20 years of age in Japan);
2.Have a diagnosis of RA, as defined by the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 or 1987 criteria for RA with disease duration of at least 6 months prior to Screening;
3.Have had an adequate trial of methotrexate (MTX) defined as having been on MTX for at least 3 months and on a stable, dose (= 8 mg/week to = 25 mg/week, not to exceed local approved dose level) for at least 6 weeks prior to Screening;
4.Have active disease, defined as: = 6 tender joints, = 6 swollen joints (based on 66 swollen joint count (SJC) and 68 tender joint count (TJC) )
5.DAS28-CRP[4] = 3.2 ;
6.Have had an inadequate response to MTX and may have failed no more than 3 other conventional non-biologic DMARDs (eg, hydroxychloroquine, oral or injectable gold, azathioprine, D penicillamine, sulfasalazine, and leflunomide or approved kinase inhibitor), and are candidates for tumor necrosis factor alpha (TNF a) inhibitor therapy;
7.Have discontinued treatment with all DMARDs, except MTX, at least 2 weeks prior to Screening;
8.Women who meet one of the following:
a.Women of childbearing potential with a negative urine pregnancy test at Screening who agree to use one or more approved methods of birth control during the study. Approved methods of birth control are: hormonal contraception, intrauterine device, diaphragm plus spermicide, condom plus spermicide. Abstinence from heterosexual intercourse will be acceptable only if it is the preferred and usual lifestyle of the subject regardless of study participation; abstinence should be practiced for the duration of the study (study duration includes the Follow-up Visit) after taking the last dose of study drug;
b.Women who have been postmenopausal for at least 2 years (with amenorrhea for at least 1 year) or have had a hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation prior to signing the informed consent; and
9.Able and willing to give written informed consent prior to performance of any study related procedures.

Part 2: Subjects must meet the following criteria to be enrolled in Part 2 of the study:
1.Completed the evaluations and achieved at least an ACR20 response at Week 24;
2.Tolerated study drug in Part 1 with no SAEs or unresolved Grade 3 or higher adverse events related to study drug.

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 414
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 206

Exclusion criteria:
1.Use of parenteral glucocorticoids within 4W prior to initiation of Screening or use of intra-articular-glucocorticoids within 4 Wprior to randomization
2.Use of oral glucocorticoids (such as > 10 mg prednisone per day (or equivalent corticosteroid), or a change in dosage within 2W prior to initiation of Screening (Note: the dose of prednisone = 10 mg per day [or equivalent corticosteroid] should remain stable throughout Screening and should be expected to remain stable during the study for the subject to be eligible)
3.Use of more than 1 NSAID or use of a single NSAID at greater than the recommended daily dose for that NSAID
4.Prior treatment with any biologic for any indication (including but not limited to: tocilizumab [RoACTEMRA, Actemra], certolizumab pegol [CIMZIA], etanercept [Enbrel], adalimumab [HUMIRA], anakinra [Kineret], abatacept [ORENCIA], infliximab [REMICADE], rituximab [MabThera, Rituxan], and golimumab [SIMPONI]); (Note: insulin for diabetes mellitus and hormonal replacement therapy and hormonal birth control are allowed)
5. Administration of a live vaccine within 4W prior to screening
6.Participation in an investigational drug or device trial within 30D prior to randomization or a period equal to 5 times the half-life of the investigational agent, whichever is longer
7.Functional class IV RA according to ACR revised classification, 1991, ie, limited ability to perform usual self care, vocational, and avocational activities
8.Diagnosis of other rheumatic disease, autoimmune disease, connective tissue disease, or immune deficiency disease (eg, psoriasis, psoriatic arthritis, primary Sjögren’s syndrome, systemic lupus erythematosus, or demyelinating diseases such as multiple sclerosis)
9.History of alcohol or drug abuse within 2Y prior to Screening
10.White blood cell count < 3500 cells/mm3, lymphocyte count < 1000 cells/mm3, platelet count = 125,000 cells/mm3, serum creatinine = 2 mg/dL (177 µmol/L), alanine transaminase or aspartate transaminase = 2.0 × the upper limit of normal of the reference range, or hemoglobin = 8.5 g/dL at Screening
11.Presence or history of malignancy (except for successfully treated non metastatic basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix)
12.Presence of TB based on positive blood test (QuantiFERON®-TB Gold Test for TB) during Screening or subjects with known recent exposure to patient with active TB; Note: QuantiFERON®-TB Gold test can be repeated one time using a fresh sample in patients with an indeterminate result or low positivity defined as Quantiferon TB Antigen minus Nil value = 0.35-2 IU/ml. If the repeat test is negative, the subject may participate in the study. If the repeat test is positive or intermediate, the subject does not qualify to participate in the study;
13.Abnormal chest x-ray obtained within 6M prior to randomization demonstrating active lung disease processes other than RA (eg, evidence of TB or another active disease process). If a chest x-ray has not been obtained within the past 6M one should be obtained during the Screening process
14.History of positive test results for fungal or other infections (e.g., histoplasmosis, coccidiomycosis) required by regional guidelines prior to start of biologic drugs within 3M prior to randomization
15.Major systemic infections (eg, positive for hepatitisB surface antigen [HBsAg], hepatitisB core antibody [HBcAb], hepatitisC virus [HCV], or human immunodeficiency virus [HIV]);

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Rheumatoid arthritis
MedDRA version: 18.1 Level: LLT Classification code 10042952 Term: Systemic rheumatoid arthritis System Organ Class: 100000004859

Intervention(s)

Product Code: CHS-0214
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Etanercept
Current Sponsor code: CHS-0214
Other descriptive name: CHS-0214
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Enbrel
Product Name: Etanercept
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): 1. The primary efficacy endpoint in Part 1 will be the percentage of subjects who achieve 20% improvement according to American College of Rheumatology Criteria (ACR20) at Week 24 compared to Baseline (week0/day0). Subjects will be considered an ACR20 responder if: compared to Baseline (week0/Day 0), they achieve: 20% decrease in swollen joint counts (SJC), 20% decrease in tender joint counts (TJC), and 20% improvement in 3 of the following 5 measures
• Hs-CRP;
• Health Assessment Questionnaire – Disability Index (HAQ DI);
• Subjects pain assessment using a visual analoguie scale (VAS);
• Subject global assessment of disease activity (SGA);
• Physicians global assessmetn of disease activity (PGA).

2.The primary response duration endpoint will be the percentage of subjects who maintain ACR20 response from week 24 (durable effect) or who have a continued improvement in response (ACR50 response, ACR70 response) and DAS28-CRP(4) to < 3.2(low disease activity) and < 2.6 (remission) assessed at weeks 28. 36 and 48

Timepoint(s) of evaluation of this end point: 1. From baseline - Day 0 to week 24
2. Part 1 - weeks 0, 4, 8, 12, 18, and 24 and for Part 2 - weeks 28, 36, and 48.

Main Objective: The objectives of Part 1 of the study are to compare the efficacy and safety of CHS 0214 manufactured in the EU, to Enbrel (EU) at 24 weeks in subjects with RA who have an inadequate response to methotrexate and no more than 3 other non-biologic disease modifying anti rheumatic drugs and who are naïve to biologic therapies.
The objectives of Part 2 of the study are to evaluate the longer term safety and the durability of response to open-label CHS 0214.

Secondary Objective: Not applicable

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy variables will include
1. ACR20 at Weeks 4, 8, 12, and 18;
2. The average percent improvement from Baseline (Week0/Day 0) in individual ACR response criteria: TJC, SJC, HAQ-DI;
3. Subject’s pain assessment (subject’s pain-VAS), SGA, PGA and hs-CRP at Weeks 4, 8, 12, 18 and 24;
4. 50% and 70% improvement according to American College of Rheumatology criteria (ACR50 and ACR70, respectively) and DAS28-CRP(4) < 3.2. ;
5. Remission rate (defined as DAS28 CRP(4) < 2.6 on all subsequent visits after DAS28 CRP(4) < 2.6 is achieved).

Timepoint(s) of evaluation of this end point: 1. Weeks 4, 8, 12 and 18
2. From Basline
3. Weeks 4, 8, 12, 18, and 24
4. Weeks 4, 8, 12, 18, and 24
5. At all subsequent study visists after required DAS28 CRP(4) is reached

Secondary ID(s)

NCT02115750

CHS-0214-02

Source(s) of Monetary Support

Baxter (Baxter International, Inc., Baxter Healthcare Corporation, Baxter Healthcare SA)

Daiichi Sankyo Company Ltd

Coherus BioSciences Inc