A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX354-C in Subjects with Rheumatoid Arthritis Partially Responsive to Methotrexate Therapy - CARAT-2

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2010-019964-36-HU
• Date of registration: 07/06/2010
• Prospective Registration: Yes
• Primary sponsor: ChemoCentryx, Inc.
• Public title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX354-C in Subjects with Rheumatoid Arthritis Partially Responsive to Methotrexate Therapy - CARAT-2
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX354-C in Subjects with Rheumatoid Arthritis Partially Responsive to Methotrexate Therapy - CARAT-2
• Date of first enrolment: 14/07/2010
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019964-36
• 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: no Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic, Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects, aged 18-75 years inclusive, with functional class I to III RA based on ACR criteria (see protocol section 11.3) for at least 3 months prior to screening; wheel-chair bound subjects or those with irreversible disease will not be eligible;
2. Subjects must have active RA, defined by a minimum of 8 swollen joints and 8 tender/painful joints (based on 66/68 joint count), at screening (see section 11.4 for joints to be included);
3. Serum C-reactive protein (CRP) above 5 mg/L at screening;
4. Must have been on methotrexate (7.5 to 25 mg/week) taken orally, subcutaneously, or intramuscularly for = 16 weeks and on a stable dose for = 8 weeks prior to randomization;
5. If on hydroxychloroquine, must have been on a stable dose for = 16 weeks prior to randomization;
6. If taking non-steroidal anti-inflammatory drugs (NSAIDs), must have been on stable doses for = 2 weeks before randomization;
7. If taking oral corticosteroids, subjects may not take more than 10 mg/day of prednisone or equivalent, and must have been on a stable dose for = 4 weeks before randomization;
8. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol;
9. Negative result of the human immunodeficiency virus (HIV) screen, the hepatitis B screen, and the hepatitis C screen;
10. Judged to be otherwise healthy by the Investigator, based on medical history, physical examination (including electrocardiogram [ECG]), and clinical laboratory assessments;
11. Female subjects of childbearing potential, and male subjects with partners of childbearing potential, may participate if adequate contraception is used during, and for at least the four weeks after, any administration of study medication. Adequate contraception is defined as usage by at least one of the partners of a barrier method of contraception, together with usage by the female partner, commencing at least three months prior to Screening, of a stable regimen of any form of hormonal contraception or an intra-uterine device. Use of abstinence alone is not considered adequate. Use of a barrier method alone is considered adequate only if the male partner was vasectomized at least six months prior to Screening. Use of a double-barrier method of contraception is acceptable.

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

Exclusion criteria:
1. Diagnosed with RA prior to 16 years of age;
2. Women who are pregnant, breastfeeding, or have a positive serum pregnancy test at screening;
3. History within one year prior to randomization of illicit drug use;
4. History of alcohol abuse at any time in the past;
5. Have received sulfasalazine, azathioprine, 6-mercaptopurine, mycophenolate mofetil, tetracycline, cyclosporine, gold, tacrolimus, sirolimus, or other disease modifying anti-rheumatic drug (DMARD) within 8 weeks of randomization;
6. Use of infliximab, adalimumab, abatacept, certolizumab, golimumab, or tocilizumab within 8 weeks of randomization;
7. Use of leflunomide within 6 months of randomization;
8. Use of etanercept or anakinra within 4 weeks of randomization;
9. Use of a B-cell depleting agent such as rituximab or ocrelizumab, or cytotoxic agents, such as cyclophosphamide or chlorambucil, within one year of randomization;
10. Currently taking cytochrome P450 inhibitors including protease inhibitors such as ritonavir, indinavir, nelfinavir, or macrolide antibiotics such as erythromycin, telithromycin, clarithromycin, or azole antifungals such as fluconazole, ketoconazole, itraconazole, or cimetidine, nefazodone, bergamottin (constituent of grapefruit juice), quercetin, aprepitant, or verapamil;
11. Currently taking cytochrome P450 inducers including St. John’s wort, rifampicin, rifabutin, rifapentin, dexamethasone, phenytoin, carbamazapine, phenobarbitol, or troglitazone;
12. Intra-articular, intravenous, or intramuscular corticosteroid injection within 4 weeks of randomization;
13. History or presence of any form of cancer within the 10 years prior to randomization, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis;
14. Evidence of tuberculosis based on chest X rays, tuberculin skin test, QuantiFERON®-TB Gold test, or T-SPOT®.TB test performed during screening;
15. Presence of Felty’s syndrome, psoriatic arthritis, gout, or other auto-immune diseases;
16. Major surgery (including joint surgery) within 12 weeks prior to randomization;
17. The subject had an infection requiring antibiotic treatment within 4 weeks of randomization;
18. Subject has any evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin > 1.5 x the upper limit of normal;
19. Subject has any evidence of renal impairment; serum creatinine > 1.5 x upper limit of normal or estimated Glomerular Filtration Rate (GFR) based on the Cockcroft-Gault equation < 30 mL/min;
20. History or presence of any medical or psychiatric condition or disease, or laboratory abnormality that, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation and may prevent the subject from completing the study; and
21. Participated in any clinical study of an investigational product including CCX354-C within 30 days or 5 times the half life of the agent, whichever is longer, prior to randomization.



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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 12.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: CCX354-C
Product Code: CCX354-C
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: CCX354-C
Other descriptive name: CCX354
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of the study is to evaluate the safety and tolerability of CCX354-C in subjects with rheumatoid arthritis (RA) who had an inadequate response to methotrexate treatment.

Secondary Objective: The secondary objectives of the study are to evaluate the efficacy of CCX354-C compared to placebo based on:
1. Change from baseline in RA Disease Activity Score 28-C-reactive protein (DAS28-CRP);
2. Proportion of subjects achieving American College of Rheumatology (ACR) 20, 50, and 70 response criteria;
3. Proportion of subjects achieving a DAS28-CRP value less than 2.6 (remission); and
4. Proportion of subjects achieving a DAS28-CRP value less than 3.2 (low disease activity).

Primary end point(s): The primary safety endpoint is the subject incidence of adverse events.
The main efficacy endpoints include:
1. Change from baseline to Week 12 in DAS28-CRP
2. ACR20, ACR50, and ACR70 Response at Week 12
3. Proportion of subjects achieving a DAS28-CRP score less than 2.6 (remission) at Week 12
4. Proportion of subjects achieving a DAS28-CRP score less than 3.2 (low disease activity) at Week 12
Pharmacokinetic Endpoints
Individual plasma concentrations of CCX354, the M11 metabolite, and possible other metabolites will be listed, and may be plotted and summarized descriptively and graphically for each treatment.
Pharmacodynamic Endpoints
The change and percent change from baseline to Week 1, 2, 4, 8, 12, and 16 in bone metabolism markers including CTx, iPTH, osteocalcin, and PINP will be determined in subjects participating in this study.

Secondary ID(s)

CL004_354

2010-019964-36-BE