A PHASE II, MULTI-CENTER, RANDOMIZED, PARALLEL GROUP, DOUBLE-BLIND, METHOTREXATE CONTROLLED STUDY TO ASSESS THE CLINICAL EFFICACY, SAFETY, AND TOLERABILITY OF CH-4051 IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS WHO HAVE SHOWN AN INADEQUATE RESPONSE TO METHOTREXATE MONOTHERAPY

• Register: EUCTR
• Last refreshed on: 19 May 2014
• Main ID: EUCTR2010-019134-27-CZ
• Date of registration: 28/06/2010
• Prospective Registration: Yes
• Primary sponsor: Chelsea Therapeutics, Inc
• Public title: A PHASE II, MULTI-CENTER, RANDOMIZED, PARALLEL GROUP, DOUBLE-BLIND, METHOTREXATE CONTROLLED STUDY TO ASSESS THE CLINICAL EFFICACY, SAFETY, AND TOLERABILITY OF CH-4051 IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS WHO HAVE SHOWN AN INADEQUATE RESPONSE TO METHOTREXATE MONOTHERAPY
• Scientific title: A PHASE II, MULTI-CENTER, RANDOMIZED, PARALLEL GROUP, DOUBLE-BLIND, METHOTREXATE CONTROLLED STUDY TO ASSESS THE CLINICAL EFFICACY, SAFETY, AND TOLERABILITY OF CH-4051 IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS WHO HAVE SHOWN AN INADEQUATE RESPONSE TO METHOTREXATE MONOTHERAPY
• Date of first enrolment: 19/10/2010
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019134-27
• 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: yes Placebo: yes Other: no

Countries of recruitment

Bulgaria, Czech Republic

Key inclusion & exclusion 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:
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.



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

Health Condition(s) or Problem(s) studied

Rhuematoid Arthritis
MedDRA version: 13.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

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: 0.3-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

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: 1.0-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

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: 3.0-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Methotrexate
Product Name: Methotrextate
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Methotrexate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Folic Acid
Product Name: Folic Acid
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Folic Acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

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.

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.

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.

Secondary ID(s)

CH-4051-RA202