A Phase II Trial Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis (Synergy)
|Rheumatoid Arthritis||Drug: Prednisolone Drug: dipyridamole Drug: Prednisone Drug: Z102 Other: placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase II, Double-Blind, Placebo-Controlled, Multi-Center, Randomized Withdrawal Design Trial Using Adaptive Randomization Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis|
- Change From Baseline in DAS28-CRP at 12 Weeks [ Time Frame: baseline to week 12 ]
The primary efficacy endpoint was the mean change in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) from baseline to Week 12.
The DAS28-CRP is a composite measure of inflammation in Rheumatoid Arthritis and incorporates a tender and swollen joint count, CRP and Patient Global Assessment of Disease Activity expressed in a Gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 suggests a low level of disease activity, while a score of >5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤3.2 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores.
- Change From Baseline in DAS28-CRP Individual Components at 12 Weeks [ Time Frame: Baseline to week 12 ]
The mean change in the individual components of the Disease Activity Score 28 using C-reactive protein (DAS28-CRP) from baseline to Week 12 which included individual assessment of Tender Joint Count (28-joint assessment), Swollen Joint Count (28-joint assessment), Patient Global Assessment of Disease Activity and absolute CRP level. In each case, higher scores indicate more disease activity.
The DAS28-CRP is a composite measure of inflammation in Rheumatoid Arthritis and incorporates a tender and swollen joint count, CRP and Patient Global Assessment of Disease Activity expressed in a Gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 suggests a low level of disease activity, while a score of >5.1 suggests a high level of disease activity.
- Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks [ Time Frame: Week 12 ]The American College of Rheumatology (ACR) 20 is a widely accepted composite index of improvement in RA proposed by the ACR (Fransen and van Riel 2009). ACR20 refers to a composite improvement of 20% in swollen joint count, tender joint count, and 3 or more of the following 5 measures:Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient Pain VAS, Patient's self-addressed disability (HAQ) (Arnet 1988 and Felson 1995), Acute-phase reactant (ESR or CRP) The ACR 50 and ACR 70 are similar tools, used to indicate 50% and 70% improvement, respectively.
- Multidimensional Assessment of Fatigue (MAF) at Week 12 [ Time Frame: week 12 ]
The Multidimensional Assessment of Fatigue (MAF) scale contains 16 items and measures four dimensions of fatigue: severity (#1-2), distress (#3), degree of interference in activities of daily living (#4-14), and timing (#15-16). Fourteen items contain numerical rating scales (#1-14) and two items have multiple-choice responses (#15-16). Respondents are asked to reflect on fatigue patterns for the past week.
To calculate the Global Fatigue Index (GFI): Convert item #15 to a 0-10 scale by multiplying each score by 2.5 and then sum items #1, 2, 3, average #4-14, and newly scored item #15.
Scores range from 1 (no fatigue) to 50 (severe fatigue). Do not assign a score to items #4-14 if respondent indicated they "do not do any activity for reasons other than fatigue." If respondents select no fatigue on item #1, assign a zero to items #2-16. Item #16 is not included in the Global Fatigue Index.
- Time to Failure (Days) [ Time Frame: Baseline to 12 weeks ]Patients will be monitored for addition of any DMARD or withdrawal due to flare. The time to failure is defined as the duration of study participation (in days) until a qualifying event or completion of study treatment, whichever comes first.
|Study Start Date:||June 2011|
|Study Completion Date:||September 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Prednisolone
Prednisolone 2.7 mg daily for 12 weeks
Prednisolone 2.7 mg daily
Active Comparator: dipyridamole
Dipyridamole 360 mg daily for 12 weeks
dipyridamole 360 mg daily
Active Comparator: prednisone
Prednisone 5 mg daily for 12 weeks
Prednisone 5 mg daily
Experimental: Z102 (2.7/360)
Prednisolone 2.7 mg plus dipyridamole 360 mg daily for 12 weeks
Prednisolone 2.7 mg plus dipyridamole 360 mg daily
Placebo Comparator: placebo
Placebo daily for 12 weeks
Please refer to this study by its ClinicalTrials.gov identifier: NCT01369745
|United States, Ohio|
|Zalicus Investigational Site|
|Toledo, Ohio, United States, 43606|
|Study Director:||Margaret Lee, PhD||Zalicus, Inc.|