A Study Comparing CRx-102 Plus Disease-modifying Anti-rheumatic Drug (DMARD) Therapy to Placebo Plus DMARD Therapy in RA

Study Overview
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Brief Summary
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This study was a Multicenter, Randomized, Blinded Study Comparing the Effect of CRx-102 Plus DMARD Therapy to that of Placebo Plus DMARD Therapy on Serum C Reactive Protein (CRP) and Cytokines in Subjects with Rheumatoid Arthritis. This Phase II, 6-week blinded study was planned for 60 subjects with moderate to severe rheumatoid arthritis (RA).

Detailed Description
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The primary objective of this study was to: • Compare the response of CRx-102 plus DMARD therapy to placebo plus DMARD therapy in lowering CRP levels in rheumatoid arthritis subjects. The secondary objectives of this study were to: Evaluate the changes in inflammatory cytokines in subjects treated with CRx-102 plus DMARD therapy to placebo plus DMARD therapy. Evaluate the efficacy of CRx-102 plus DMARD therapy to placebo plus DMARD therapy using ACR-20 and DAS28 indices as well as fatigue scales.

Official Title
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A Multicenter, Randomized, Blinded Study Comparing the Effect of CRx-102 Plus DMARD Therapy to That of Placebo Plus DMARD Therapy on Serum C Reactive Protein (CRP) and Cytokines in Subjects With RA

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: CRx-102
* Drug: Placebo
* Drug: DMARD Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Was 18 years of age of older Had moderate to severe RA Had at least 3 swollen joints (maximum 28) and 3 tender joints (maximum 28) Had a Baseline CRP level of at least 2.2 mg/L and a DAS28 score >4.5 Had been on DMARD therapy for at least 3 months and have been on a stable dose of DMARD therapy for at least 28 days prior to enrollment Had a negative pregnancy test (females) Was not taking glucocorticoids at screening Exclusion Criteria: Female subject is pregnant or lactating or of child bearing potential not using acceptable methods of birth control (barriers or abstinence). Female subjects using hormonal birth control are not to be enrolled. Subject is currently taking any steroids (glucocorticoids). All glucocorticoids must be discontinued for at least one month prior to entering study. Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering the study. Subject is currently taking more than 81 mg of aspirin daily. Subject is currently taking a statin, unless she/he has been on a stable dose of the same statin for at least 3 months prior to entering into the trial. Subject has any active infections or recent surgical procedures within 30 days of study initiation. Subject has uncontrolled diabetes mellitus as defined by a HbA1C value ≥ 7.0%. Subject knowingly has HIV or Hepatitis. Subject has undergone administration of any investigational drug within 30 days of study initiation. Subject has a history of hypersensitivity to steroids and/or dipyridamole. Subject has limited mental capacity or language skills such that simple instructions cannot be followed or information regarding adverse events cannot be provided.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRx-102 plus DMARD therapy<br> | Drug: CRx-102<br> <br> * Other names: Prednisolone plus dipyridamole;Drug: DMARD Therapy<br>* DMARD therapy can include methotrexate or other DMARD therapy<br>* Other names: Disease modifying anti-rheumatic drug therapy;|
| Placebo Comparator: Placebo plus DMARD therapy<br> | Drug: Placebo<br> <br> * Other names: sugar pill;Drug: DMARD Therapy<br>* DMARD therapy can include methotrexate or other DMARD therapy<br>* Other names: Disease modifying anti-rheumatic drug therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CRP From Baseline to Day 42 | The primary efficacy variable in this study was the change in CRP from Baseline (Day 1/Visit 2) to End of Study (Day 42/Visit 5). Blood samples for the analysis of serum CRP were taken at each visit. | Baseline and Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of ACR 20 Scores at End of Study (Day 42/Visit 5) | The percentage of subjects in each group that achieved an ACR 20 response on Day 42 | Day 42 | 
| Change in DAS28 Score From Baseline to Day 42 | To calculate the DAS28, the number of swollen joints and tender joints should be assessed using 28-joint counts, the ESR should have been measured in mm/hour, and the patient's general health (GH) or global disease activity measured on a Visual Analog Scale (VAS) of 100 mm must be obtained. Using these data, the DAS28 could be calculated using the following formula: DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * GH. The DAS28 provides a number between 0 and 10 that indicates the current activity of RA in the subject. A DAS28 above 5.1 means high disease activity and below 3.2 indicates low activity. Remission is achieved when a DAS28 score is lower than 2.6. The DAS28 measurements were to be taken at each visit. | Baseline and Day 42 | 
| Change in Fatigue (MAF Scale) Score From Baseline to Day 42 | The Multidimensional Assessment of Fatigue (MAF) scale is a self-administered, 16 item questionnaire to measure self-reported fatigue (http://www.son.washington.edu/research/maf/). The following steps were used to calculate a single score ranging from 1 (no fatigue) to 50 (severe fatigue). Convert item #15 to a 0 to 10 scale by multiplying each score by 2.5 Sum items #1, 2, and 3 Average items #4 through 14 Add results from above Steps 1 through 3 to obtain a single score A score was not be assigned to items #4 through 14 if a respondent indicated they did not engage any activity for reasons other than fatigue. If respondent selected no fatigue on item #1, a 0 was to be assigned to items #2 through 16; item #16 was not included in the global fatigue index. | Baseline and Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RA, Rheumatoid Arthritis, DMARD, CRP