A Study to Assess CH1504 in Patients With Active Rheumatoid Arthritis

NCT00658047 | Completed Phase 2 DMC

• 1 other identifier: CH-1504-201
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to assess the clinical effect of CH-1504 at doses of 0.25, 0.5 and 1.0 mg per day in patients with active rheumatoid arthritis by determining the proportion of patients achieving an American College of Rheumatology (ACR) 20% improvement response.

Conditions

Arthritis, Rheumatoid

Keywords

Arthritis, Rheumatoid; Phase II; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Assess the clinical effect of CH-1504 (0.25, 0.5, and 1.0 mg po daily) by determining the proportion of patients achieving an ACR20 response.

  3 months of treatment

Secondary Outcomes (5)

• Assess the clinical efficacy of CH-1504 by proportion of patients achieving ACR50 and ACR70 responses.

  3 months of treatment

• Assess the clinical efficacy of CH-1504 using EULAR "good" and "moderate" response criteria.

  3 months of treatment

• Assess the clinical efficacy of CH-1504 using the difference from baseline of ACR core set and DAS28 of measures.

  3 months of treatment

• Evaluate the safety and tolerability of CH-1504 in RA patients as determined by the frequency and severity of adverse events, laboratory abnormalities, and dropouts.

  3 months of treatment

• Identify the dose response relationship of CH-1504.

  3 months of treatment

Study Arms (4)

0.25 mg CH-1504

EXPERIMENTAL

0.25 mg CH-1504

Drug: CH-1504

0.5 mg CH-1504

EXPERIMENTAL

0.5 mg CH-1504

Drug: CH-1504

1.0 mg CH-1504

EXPERIMENTAL

1.0 mg CH-1504

Drug: CH-1504

Methotrexate

ACTIVE COMPARATOR

Methotrexate (MTX) 10 mg/week for 2 weeks, 15 mg/week for 2 weeks, 20 mg/week for 8 weeks

Drug: Methotrexate (MTX)

Interventions

CH-1504 DRUG

Comparison of different doses of CH-1504

0.25 mg CH-1504; 0.5 mg CH-1504; 1.0 mg CH-1504

Methotrexate (MTX) DRUG

10mg/week for 2 weeks escalated to 15mg/week for 2 weeks escalated to 20mg/week for 8 weeks

Also known as: amethopterin (previous name for MTX)

Methotrexate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Inclusion; To be eligible for inclusion, each patient must fulfill the following criteria: * Patients must be between the ages of 18 and 80; * Have been diagnosed with active rheumatoid arthritis according to ACR criteria; * 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 \> 20 mm/Hr; * Morning stiffness \> 45 min. at screening; * Patients must have blood test values per the following criteria: * ALT, AST \< 1.2 U/l x ULN * Albumin \> 2.5 g/dl * Prothrombin Time \< 1.2 INR * Hb \> 9.0 g/dl * Hct \> 35% * WBC \> 3000 μl (mm3) * Neutrophils \> 1000 μl (mm3) * Platelets \> 100000 μl * Creatinine \< 1.2 mg/dl * Patients must have voluntarily signed the informed consent Exclusion; Patients are not eligible for this study if they fulfill one or more of the following criteria: * Patients who received previous methotrexate therapy; * Patients who received previous therapy with any biologic agent; * Previous biologic therapy for a disease other than RA is permitted so long as their last dose was more than 120 days prior to baseline; * Patients currently taking sulfasalazine; * Previous sulfasalazine therapy is permitted so long as their last dose was more than 30 days prior to baseline; * Patients currently taking hydroxychloroquine; * Previous hydroxychloroquine is permitted so long as their last dose was more than 120 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, Hepatitis B or C; * Patients who consume more than 7 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 a chest X-ray that indicates the presence of pulmonary fibrosis (Chest x-ray may be taken with in 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 considered by the investigator to be an unsuitable candidate to receive CH-1504; * Wheelchair or bed-bound patients.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (1)

The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease

Toronto, Ontario, M5G 1X5, Canada

Location

Related Publications (1)

• Keystone EC, Shirinsky VS, Simon LS, Pedder S, Hewitt LA; CH-1504 Study Group. Efficacy and safety of CH-1504, a metabolically stable antifolate, in patients with active rheumatoid arthritis: results of a phase II multicenter randomized study. J Rheumatol. 2011 Sep;38(9):1875-83. doi: 10.3899/jrheum.101038. Epub 2011 Jul 1.

  PMID: 21724705 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

4'-methylene-5,8,10-trideazaaminopterin; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Edward Keystone, MD

  The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 14, 2008
• Study Start: April 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: June 1, 2009
• Last Updated: April 15, 2013

Record last verified: 2013-04

Locations

CA (1)