Multicenter Study to Evaluate CRx-102 vs. Each of Its Components to Treat Active Rheumatoid Arthritis

NCT00551707 | Completed Phase 2 Results DMC

• 1 other identifier: CRx-102-007
• Study Type: interventional
• Target: 51
• Locations: 12 countries
• Sites: 48

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.

Conditions

Rheumatoid Arthritis

Keywords

CombinatoRx; CRx-102; Rheumatoid Arthritis; Prednisolone; Dipyridamole; ACR20

Outcome Measures

Primary Outcomes (1)

• Absolute C-reactive Protein (CRP) Values at Day 98 - As Treated Population

  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 CRP values in the As-Treated population were calculated.

  Day 98

Secondary Outcomes (3)

• Percent Change From Baseline to Day 98 in C-reactive Protein (CRP) Values - As Treated Population

  baseline to day 98

• 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

  baseline to day 98

• To Assess the Efficacy of CRx-102 Compared to Placebo Using ACR 20 Calculated From Baseline to Day 98

  baseline to 98 Days

Study Arms (5)

CRx-102 (2.7/180)

EXPERIMENTAL

CRx-102 dose 1 total daily dose during treatment period (days 14-98) 2.7 mg prednisolone plus 180 mg dipyridamole administered as 1.8 mg prednisolone plus 90 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 90 mg dipyridamole at 1 PM titration dose (days 0-13) 2.7 mg prednisolone plus 90 mg dipyridamole administered as 1.8 mg prednisolone plus 45 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 45 mg dipyridamole at 1 PM

Drug: CRx-102 (2.7/180)

CRx-102 (2.7/360)

EXPERIMENTAL

CRx-102 Dose 2 total daily dose during treatment period (days 14-98) 2.7 mg prednisolone plus 360 mg dipyridamole administered as 1.8 mg prednisolone plus 180 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 180 mg dipyridamole at 1 PM titration dose 1 (days 0-6) 2.7 mg prednisolone plus 90 mg dipyridamole administered as 1.8 mg prednisolone plus 45 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 45 mg dipyridamole at 1 PM titration dose 2 (days 7-13) 2.7 mg prednisolone plus 180 mg dipyridamole administered as 1.8 mg prednisolone plus 90 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 90 mg dipyridamole at 1 PM

Drug: CRx-102 (2.7/180); Drug: CRx-102 (2.7/360)

Prednisolone

ACTIVE COMPARATOR

treatment dose ( days 0-98) total daily dose of 2.7 mg prednisolone administered as 1.8 mg prednisolone at 8 AM and 0.9 mg prednisolone at 1 PM

Drug: prednisolone

Dipyridamole

ACTIVE COMPARATOR

total daily dose during treatment period (days 14-98) 360 mg dipyridamole administered as 180 mg dipyridamole at 8 AM and and 180 mg dipyridamole at 1 PM titration dose 1 (days 0-6) 90 mg dipyridamole administered 45 mg dipyridamole at 8 AM and 45 mg dipyridamole at 1 PM titration dose 2 (days 7-13) 180 mg dipyridamole administered as 90 mg dipyridamole at 8 AM and 90 mg dipyridamole at 1 PM

Drug: dipyridamole

Placebo

PLACEBO COMPARATOR

placebo administered twice per day at 8 AM and 1 PM

Drug: placebo

Interventions

CRx-102 (2.7/180) DRUG

prednisolone 2.7 mg plus dipyridamole 180 mg

Also known as: prednisolone 2.7 mg plus dipyridamole 180 mg

CRx-102 (2.7/180); CRx-102 (2.7/360)

prednisolone DRUG

prednisolone (2.7 mg)

Prednisolone

dipyridamole DRUG

dipyridamole 360 mg

Also known as: dipyridamole 360 mg

Dipyridamole

placebo DRUG

placebo

Placebo

CRx-102 (2.7/360) DRUG

Prednisolone 2.7 mg plus Dipyridamole 360 mg

Also known as: Prednisolone 2.7 mg plus Dipyridamole 360 mg

CRx-102 (2.7/360)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Zalicus: lead

Study Sites (48)

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Phoenix, Arizona, United States

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Little Rock, Arkansas, United States

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Anaheim, California, United States

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La Jolla, California, United States

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Westlake Village, California, United States

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Palm Harbor, Florida, United States

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Elizabethtown, Kentucky, United States

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Haddon Heights, New Jersey, United States

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Mayfield Village, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Dallas, Texas, United States

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Buenos Aires, Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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San Jan, Argentina

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San Miguel de Tucumán, Argentina

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Winnipeg, Manitoba, Canada

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St. John's, Newfoundland and Labrador, Canada

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Hamilton, Ontario, Canada

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Windsor, Ontario, Canada

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Tallinn, Estonia

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Tartu, Estonia

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Békéscsaba, Hungary

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Esztergom, Hungary

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Szolnok, Hungary

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Kaunas, Lithuania

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Vilnius, Lithuania

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Aguascalientes, Aguascalientes, Mexico

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Vallarta Norte, Guadalajara, Mexico

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Bialystok, Poland

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Elblag, Poland

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Katowice, Poland

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Krakow, Poland

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Lublin, Poland

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Poznan, Poland

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Torun, Poland

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Warsaw, Poland

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Bucharest, Romania

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Cluj-Napoca, Romania

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Timișoara, Romania

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Moscow, Russia

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Saint Petersburg, Russia

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Belgrade, Serbia

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Niška Banja, Serbia

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Pretoria, Gauteng, South Africa

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Cape Town, Western Cape, South Africa

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Worcester, Western Cape, South Africa

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

dipyridamole, prednisolone drug combination; Prednisolone; Dipyridamole

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Margaret Lee, PhD
• Organization: Zalicus

mlee@zalicus.com

617-301-7142

Study Officials

• Margaret Lee, PhD

  Zalicus

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 29, 2007
• First Posted: October 31, 2007
• Study Start: October 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: January 1, 2009
• Last Updated: April 29, 2014
• Results First Posted: April 29, 2014

Record last verified: 2014-03

Locations

ES (2); RO (3); RU (2); SE (2); CA (4); HU (3); AR (4); ME (2); PL (8); ZA (3); US (13); LI (2)