A Study Comparing Sirukumab (CNTO 136) Monotherapy with Adalimumab (HUMIRA®) Monotherapy in the Treatment of Active Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 12 September 2016
• Main ID: EUCTR2013-001417-32-BG
• Date of registration: 16/09/2014
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: A Study Comparing Sirukumab (CNTO 136) Monotherapy with Adalimumab (HUMIRA®) Monotherapy in the Treatment of Active Rheumatoid Arthritis
• Scientific title: A Multicenter, Randomized, Double-blind, Parallel Group Study of CNTO 136 (sirukumab) Administered Subcutaneously as Monotherapy Compared With Adalimumab Monotherapy, in Subjects with Active Rheumatoid Arthritis - SIRROUND-H
• Date of first enrolment: 27/11/2014
• Target sample size: 510
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001417-32
• 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: 3
• 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, Brazil, Bulgaria, Chile, Colombia, Germany, Hungary, Lithuania, Mexico, Moldova, Republic of, Peru, Poland, Romania, Russian Federation, Serbia, South Africa, Spain, Ukraine, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have a diagnosis of rheumatoid arthritis (RA) for at least 6 months before screening

2. Have moderately to severely active RA with at least 8 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline

3. Have previous or current treatment with methotrexate (MTX) and are considered intolerant to MTX (including MTX-naïve subjects for whom it is inappropriate to administer MTX), and/or are considered inappropriate for treatment with MTX, and/or an inadequate responder to methotrexate

4. Must not have received MTX or any other non-biologic DMARD including but not limited to sulfasalazine, hydroxychloroquine, chloroquine, and bucillamine for at least 2 weeks prior to the first administration of the study agent

5. C-reactive protein >= 10.00 mg/L or erythrocyte sedimentation rate >=28 mm/hr at screening
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 423
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 87

Exclusion criteria:
1. Has Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis

2. Has ever received biologic therapy for RA, including but not limited to the following: TNF-alpha inhibitors, tocilizumab, rituximab, anakinra, abatacept

3. Has ever used tofacitinib therapy or any other JAK inhibitor

4. Has received intra-articular, intramuscular, or IV corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration

5. Has received leflunomide within 24 months before the first study agent administration and has not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable


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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 18.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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

Intervention(s)

Product Name: Sirukumab
Product Code: CNTO136
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Sirukumab
Other descriptive name: CNTO 136
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: Sirukumab
Product Code: CNTO136
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Sirukumab
Other descriptive name: CNTO 136
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Humira
Product Name: Adalimumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: The primary objective is to demonstrate the superior efficacy of sirukumab monotherapy compared with adalimumab monotherapy in biologic naïve subjects with active RA who are intolerant to MTX, who are considered inappropriate for continued treatment with MTX or who are inadequate responders to MTX.

Secondary Objective: The secondary objectives are to assess the following for sirukumab:
- Safety
- Physical function
- Pharmacokinetics, pharmacodynamics, and immunogenicity

Primary end point(s): 1. Change from baseline in Disease Activity Index Score 28 using erythrocyte sedimentation rate [DAS28 (ESR)]

2. Percentage of subjects with an American College of Rheumatology 50 (ACR 50) response

Timepoint(s) of evaluation of this end point: 1, 2) at week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1, 2) at week 24

3, 4, 6, 8, 11, 13, 15-20, 22-25) at weeks 24 and 52

5, 9, 10, 14, 26) at week 52

7, 12) over time by time point

21) from week 0 through week 24

Secondary end point(s): Major Secondary Endpoints
1. Percentage of subjects with DAS28 (ESR) remission

2. Percentage of subjects with an ACR 20 response

Other secondary endpoints:
3. Proportion of subjects with DAS (ESR) response at Weeks 24 and 52

4. Proportion of subjects with DAS28 (CRP) response at Weeks 24 and 52

5. Proportion of subjects with DAS (ESR) remission at Week 52

6. Proportion of subjects with DAS28 (CRP) remission at Weeks 24 and 52

7. Change from baseline in DAS28 (ESR) and DAS28 (CRP) over time by time point

8. Proportion of patients with EULAR low disease (DAS28 < 3.2) activity at Weeks 24 and 52

9. Proportion of subjects who achieve ACR 20 response at Weeks 52

10. Proportion of subjects who achieve ACR 50 response at Week 52

11. Proportion of subjects who achieve ACR 70 responses at Weeks 24 and 52

12. Proportion of subjects who achieve ACR 20, ACR 50, and ACR 70 response over time by time point

13. Percent improvement from baseline in ACR components at Weeks 24 and 52

14. Proportion of subjects who achieve major clinical response by Week 52

15. Proportion of subjects with SDAI-based ACR/EULAR remission at Weeks 24 and 52

16. Proportion of subjects with Boolean-based ACR/EULAR remission at Weeks 24 and 52

17. CDAI remission/low disease activity at Weeks 24 and 52

18. Change from baseline in SDAI at Weeks 24 and 52

19. Change from baseline in CDAI at Weeks 24 and 52

20. Change from baseline in HAQ-DI score at Weeks 24 and 52

21. AUC of change from baseline in HAQ-DI score from Week 0 through Week 24

22. Proportion of HAQ-DI responders (ie, those who have a change from baseline of > 0.22 in HAQ-DI score) at Weeks 24 and 52

23. Change from baseline in duration of morning stiffness at Weeks 24 and 52

24. Change from baseline in physical and mental component scores and in domain scores of SF-36 at Weeks 24 and 52

25. Change from baseline in FACIT-Fatigue at Weeks 24 and 52

26. Change from baseline in EQ-5D VAS and in EQ-5D index at Week 52

Secondary ID(s)

NCT02019472

CNTO136ARA3005

2013-001417-32-DE

Source(s) of Monetary Support

Janssen Research and Development, LLC