Rhuematoid Arthritis MedDRA version: 13.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: CH-4051
Product Code: CH-4051
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Dipotassium Salt
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
Chelsea Therapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for inclusion, each patient must fulfill the following 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: o C-reactive protein > 1.0 mg/dl at screening; o 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; o Patients that are not RF or Anti-CCP positive may be entered into the study only after consultation with and approval by the Medical Monitor • Patients must have voluntarily signed the informed consent form. 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
Exclusion criteria: Patients are not eligible for this study if they fulfill one or more of the following criteria: • Patients who received previous therapy with any biologic agent; • Patients currently taking any disease modifying anti-rheumatic drug (DMARD) other than MTX; o Previous non-biologic DMARD therapy is permitted as long as their last dose was at least 28 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 who are 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; o Patients with a serum creatinine level > 1.5 mg/dl at screening; o 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Demonstrate clinical efficacy of one or more doses of CH-4051 (0.3 mg, 1.0 mg, 3.0 mg and 3.0 mg with 1 mg folic acid supplementation p.o. daily) compared to MTX (20 mg/week) with 1.0 mg of folic acid supplementation p.o. daily as measured by the Hybrid ACR score, followed in a hierarchical step-down analysis of the Proportion of patients achieving ACR20.;Secondary Objective: • Assess the clinical efficacy of CH-4051 using DAS28 scores; • Assess the clinical efficacy of CH-4051 through analyses of the Area Under the Curve (AUC) of the Hybrid and DAS28 scores; • Proportion of patients achieving ACR50 and ACR70 response; • Assess the clinical efficacy of CH-4051 through analyses of the Area Under the Curve (AUC) of the ACR20, 50 and 70; • Assess linear trends in the Hybrid ACR, DAS28 and ACR20 scores across dose groups; • Assess the clinical efficacy of CH-4051 using EULAR “good” and “moderate” response criteria; • Assess the clinical efficacy of CH-4051 using mean changes from baseline in the components of the ACR and DAS28 response criteria; • Assess the clinical efficacy of CH-4051 using mean change from baseline of morning stiffness; • Evaluate the 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. ;Primary end point(s): The hACR will be summarized at each visit. A one-way analysis of variance (ANOVA) will be employed to assess treatment effect at Week 12. Each of the CH-4051 treatments will be compared to the MTX. Any changes between Weeks 12 and 16 will be noted. The co-primary end point, ACR20 will be analyzed using a “gatekeeper” function only if the hACR endpoint reaches statistical significance (p< 0.05). The ACR20 will be summarized at each visit. Differences between groups at week 12 will be compared using a Pearson’s Chi-squared test. Any changes between Weeks 12 and 16 will be noted. Details will be provided in the SAP. | — |
Countries
Bulgaria, Czech Republic
Outcome results
None listed