Clinical trial NCT01116141: A Study of CH-4051 in Patients With Rheumatoid Arthritis (RA)
Official title: A Phase II, Multi-center, Randomized, Parallel Group, Double-blind, MTX Controlled Study to Assess the Clinical Efficacy, Safety and Tolerability of CH-4051 in Patients With Active RA Who Have Shown an Inadequate Response to MTX Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
MTX
CH-405
antifolates
Lead sponsor: Chelsea Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-05-04
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if CH-4051 is a safe and effective treatment for rheumatoid arthritis.

Detailed description: Multi-center, multi-national, double-blind, randomized, active-controlled (MTX), 3-month study with 4 doses of CH-4051 (0.3 mg, 1.0 mg, 3.0 mg and 3.0 mg with 1mg of folic acid supplementation p.o. daily) compared to a "standard" dose of MTX at 20 mg per week with 1 mg of folic acid supplementation p.o. daily. This study will be conducted in two parts:

Part A: Patients will be randomized to 0.3 mg CH-4051, 1.0 mg CH-4051 or MTX. Part B: Patients will not be randomized into Part B until the Data Monitoring Committee has reviewed safety data from the Part A when approximately 25 patients (10 patients in each CH-4051 dose groups and 5 patients in the MTX groups) have completed 3 months of treatment. At this time the DMC will make a recommendation whether or not to commence randomization to 3.0 mg CH-4051, 3.0 mg CH-4051 with 1.0 mg of folic acid.

Eligibility criteria: Inclusion Criteria:

* Patients must be between the ages of 18 and 80;
* Have diagnosed active rheumatoid arthritis according to ACR criteria functional class I-III;
* Have at least 6 swollen joints (max = 66) and 6 tender joints (max = 68) at screening and baseline visits;
* Patients must have at least one of the following:
* C-reactive protein \> 1.0 mg/dl at screening;
* erythrocyte sedimentation rate \> 28 mm/Hr;
* Patients must have been taking methotrexate between 15 and 25 mg/week for at least 3 months and at a stable dose for at least 6 weeks;
* Patients must be either Rheumatoid Factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) positive;
* Patients must have voluntarily signed the informed consent.

Exclusion Criteria:

* Patients who received previous therapy with any biologic agent;
* Patients currently taking any disease modifying anti-rheumatic drug (DMARD) other than MTX;
* Previous non-biologic DMARD therapy is permitted as long as their last dose was at least 30 days prior to baseline;
* Female patients of child bearing potential who are pregnant or who are not using two methods of contraception (at least one barrier: i.e. condom) with their partner;
* Male patients who are sexually active and not using two methods of contraception (at least one barrier: i.e. condom) with their partner;
* Patients with any current active infection or infections requiring IV drug therapy within 30 days of baseline or oral therapy within 15 days of Baseline;
* Patients that have had any surgical procedures within 30 days of baseline;
* Patients with a history of HIV;
* Patients with Hepatitis B surface antigen positive and/or Hepatitis C antibody positive;
* Patients who consume more than 4 units of alcohol per week (1 unit = 5 ounces/150 ml of wine = 1.5 ounces/45 ml spirits = 12 ounces/360 ml of beer);
* Patients currently receiving any investigational drug or have received an investigational drug within 30 days of baseline or 5 half-lives of the investigational drug (whichever is longer);
* Patients with a history of cancer within the past 5 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ;
* Patients with a history of, or any, disease associated with an inflammatory arthritis other than RA;
* Patients with pulmonary fibrosis (Chest x-ray must be taken within 28 days of screening);
* Patients receiving probenecid;
* Patients who have received any steroid injections within 30 days of baseline;
* Patients with concomitant diseases that are unstable (i.e. cardiac, pulmonary) or that may affect drug activity (i.e. absorption, reactions, change in kinetics);
* Patients, in the investigator's opinion, that have any significant renal or hepatic impairment;
* Patients with a serum creatinine level \> 1.5 mg/dl at screening;
* Patients with an ALT \>1.5 ULN at screening;
* Patients considered by the investigator to be an unsuitable candidate to receive CH-4051;
* Wheelchair or bed-bound patients.

Primary outcomes:
measure: Co-primary: Hybrid American College of Rheumatology response criteria (hACR)followed by the ACR20
timeFrame: 12 weeks
Secondary outcomes:
measure: DAS28
timeFrame: 12 weeks
measure: ACR response criteria
timeFrame: 12 weeks
measure: Morning stiffness
timeFrame: 12 weeks
measure: Safety and tolerability of CH-4051 in RA patients as determined by the frequency and severity of adverse events, laboratory abnormalities, and dropouts due to AEs
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
name: Arthur A Kavanaugh, MD
role: PRINCIPAL_INVESTIGATOR
References: