Clinical trial NCT00551707: Multicenter Study to Evaluate CRx-102 vs. Each of Its Components to Treat Active Rheumatoid Arthritis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Superiority of CRx-102 Over Each of Its Components When Given to Subjects With Active Rheumatoid Arthritis (RA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: CombinatoRx
CRx-102
Rheumatoid Arthritis
Prednisolone
Dipyridamole
ACR20
Lead sponsor: Zalicus
Sponsor class: INDUSTRY
First posted: 2007-10-31
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: CRx-102 is a synergistic combination drug candidate containing the cardiovascular drug dipyridamole and a very low dose of the glucocorticoid prednisolone. CRx-102 is believed to work through a novel mechanism of action in which dipyridamole selectively amplifies the anti-inflammatory and immunomodulatory activities of the glucocorticoid without replicating the dose-dependent adverse effects. CRx-102 has been associated with clinical benefit in proof of concept studies in subjects with hand Osteoarthritis (OA) and Rheumatoid Arthritis (RA).

In this trial, CRx-102 will be given to subjects with active RA as an add-on therapy to existing stable doses of Disease Modifying Anti-Rheumatic Drugs (DMARDs) including methotrexate (MTX), sulfasalazine, hydroxychloroquine, leflunomide or azathioprine. MTX in combination with other DMARDs (e.g., sulfasalazine or hydroxychloroquine) will be permitted to reflect the current standard of care practices within rheumatology.

Detailed description: The study was discontinued before the enrollment objective was met. Preliminary review of the efficacy dataset revealed that the efficacy dataset was not robust enough to support an extensive formal efficacy analysis as described in the SAP. Therefore, only the CRP values over time and the percent change in C-reactive protein (CRP) values in the As-Treated population were calculated.

Eligibility criteria: Inclusion Criteria:

* Subject must voluntarily give written informed consent
* Subject must be ≥ 18 years of age
* Subject must have RA (ACR criteria)
* Subject must have at least 4 swollen joints and at least 6 tender joints at screening and baseline (28 joint count)
* Subject must have a CRP \> Upper Limit of Normal at screening
* Subject must have been on DMARD or DMARD combination (e.g. MTX + hydroxychloroquine) for at least 3 months and be on a stable dose of DMARD(s) for at least 6 weeks prior to screening.
* For MTX subjects: MTX ≥ 7.5 mg weekly (po/sc/im) and willing to take folic acid or folinic acid supplementation
* Subject willing to take concomitant multivitamin or the equivalent of 400 I.U. vitamin D and the equivalent of 1000 mg of elemental calcium daily

Exclusion Criteria:

* History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease
* Wheelchair or bed bound
* History of osteoporotic fracture
* History of malignancy within the past 10 years. However, subjects with a history of treated or excised basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate
* History of lymphoma or chronic leukemia
* Moles or lesions that are currently undiagnosed, but are suspicious for malignancy
* Surgery within the previous 3 months (except for minor dental and cosmetic)
* History of drug or alcohol abuse (as defined by the Investigator)
* History of bleeding disorder
* History of gastrointestinal bleeding within 5 years of screening
* History of severe migraines or headaches
* History of glaucoma
* Active diabetic retinopathy
* Visually compromising cataract
* History of opportunistic infection within the previous 12 months
* Active Tuberculosis (TB)
* Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to screening
* Fever or symptomatic viral or bacterial infection within 2 weeks prior to screening
* Positive for Hepatitis C virus (HCV) antibody
* Positive for HBsAg
* Known positive HIV antibody
* Has a history of hypersensitivity to glucocorticoids and/or dipyridamole
* Treatment with oral, intra-articular, intramuscular, or intravenous glucocorticoids within 6 weeks prior to screening; inhaled glucocorticoid is permitted
* Treatment with any tumor necrosis factor-alpha (TNFα) biologic, anakinra or abatacept within 2 months prior to screening
* Treatment with rituximab
* Treatment with another investigational drug 3 months prior to screening
* Treatment with anticoagulants including: dipyridamole, warfarin, clopidogrel, ticlopidine; Acetylsalicylic acid \> 150 mg per day
* Treatment with any concomitant medications that have not been at a stable dose for at least 28 days prior to screening
* Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) laboratory values that exceed 1.5 x ULN
* HbA1C value of \> 7.0%
* Current enrollment in any other study with investigational drug or device
* Female subject who is pregnant or lactating or of child bearing potential and not using acceptable methods of contraception (birth control pills, barriers or abstinence)
* Unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's return for follow-up visits on schedule
* Other unspecified reasons that, in the opinion of the Investigator or sponsor make the subject unsuitable for enrollment

Primary outcomes:
measure: Absolute C-reactive Protein (CRP) Values at Day 98 - As Treated Population
timeFrame: Day 98
Secondary outcomes:
measure: Percent Change From Baseline to Day 98 in C-reactive Protein (CRP) Values - As Treated Population
timeFrame: baseline to day 98
measure: To Assess the Superiority of CRx-102 Compared to Prednisolone and Dipyridamole Using American College of Rheumatology Rating Scale (20% or More Improvement; ACR20) Calculated From Baseline to Day 98 in Subjects With Active Rheumatoid Arthritis
timeFrame: baseline to day 98
measure: To Assess the Efficacy of CRx-102 Compared to Placebo Using ACR 20 Calculated From Baseline to Day 98
timeFrame: baseline to 98 Days
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Palm Harbor
country: United States
state: Florida
city: Elizabethtown
country: United States
state: Kentucky
city: Haddon Heights
country: United States
state: New Jersey
city: Mayfield Village
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Dallas
country: United States
state: Texas
city: Rosario
country: Argentina
state: Santa Fe
city: Buenos Aires
country: Argentina
city: San Jan
country: Argentina
city: San Miguel de Tucuman
country: Argentina
city: Winnipeg
country: Canada
state: Manitoba
city: St. John's
country: Canada
state: Newfoundland and Labrador
city: Hamilton
country: Canada
state: Ontario
city: Windsor
country: Canada
state: Ontario
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Bekescsaba
country: Hungary
city: Esztergom
country: Hungary
city: Szolnok
country: Hungary
city: Kaunas
country: Lithuania
city: Vilnius
country: Lithuania
city: Aguas Calientes
country: Mexico
state: Aguascalientes
city: Vallarta Norte
country: Mexico
state: Guadalajara
city: Bialystok
country: Poland
city: Elblag
country: Poland
city: Katowice
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Bucuresti
country: Romania
city: Cluj Napoca
country: Romania
city: Timisoara
country: Romania
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Belgrade
country: Serbia
city: Niska Banja
country: Serbia
city: Pretoria
country: South Africa
state: Gauteng
city: Cape Town
country: South Africa
state: Western Cape
city: Worcester
country: South Africa
state: Western Cape
Study officials:
affiliation: Zalicus
name: Margaret Lee, PhD
role: STUDY_DIRECTOR
References: