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

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

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).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: CRx-102; Drug: DMARD Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zalicus

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: September 3, 2008
• First Submitted That Met QC Criteria: September 4, 2008
• First Posted (Estimate): September 5, 2008

Study Record Updates

• Last Update Posted (Estimate): May 20, 2014
• Last Update Submitted That Met QC Criteria: April 22, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; RA; DMARD; CRP
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Platelet Aggregation Inhibitors; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Phosphodiesterase Inhibitors; Prednisolone; Dipyridamole; Antirheumatic Agents
• Other Study ID Numbers: CRx-102-002