A Study of CH-4051 in Patients With Rheumatoid Arthritis (RA)

NCT ID: NCT01116141

Last Updated: 2013-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2012-05-31

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Methotrexate (MTX) + Folic Acid

20 mg MTX weekly + 1 mg folic acid daily

Group Type: ACTIVE_COMPARATOR

Methotrexate (MTX)

Intervention Type: DRUG

20 mg MTX weekly

Folic Acid

Intervention Type: DRUG

1 mg folic acid daily

0.3 mg CH-4051

0.3 mg CH-4051 daily

Group Type: EXPERIMENTAL

CH-4051

Intervention Type: DRUG

Different doses CH-4051 to be compared

1.0 mg CH-4051

1.0 mg CH-4051 daily

Group Type: EXPERIMENTAL

CH-4051

Intervention Type: DRUG

Different doses CH-4051 to be compared

3.0 mg CH-4051

3.0 mg CH-4051 daily

Group Type: EXPERIMENTAL

CH-4051

Intervention Type: DRUG

Different doses CH-4051 to be compared

3.0 mg CH-4051 + folic acid

3.0 mg CH-4051 + 1.0 mg folic acid daily

Group Type: EXPERIMENTAL

CH-4051

Intervention Type: DRUG

Different doses CH-4051 to be compared

Folic Acid

Intervention Type: DRUG

1 mg folic acid daily

Interventions

CH-4051

Different doses CH-4051 to be compared

Intervention Type: DRUG

Methotrexate (MTX)

20 mg MTX weekly

Intervention Type: DRUG

Folic Acid

1 mg folic acid daily

Intervention Type: DRUG

Other Intervention Names

amethopterin; folate

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chelsea Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arthur A Kavanaugh, MD

Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

CH-4051-RA202

Identifier Type: -

Identifier Source: org_study_id