A Phase II Trial Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis (Synergy)
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|ClinicalTrials.gov Identifier: NCT01369745|
Recruitment Status : Completed
First Posted : June 9, 2011
Results First Posted : April 30, 2014
Last Update Posted : May 15, 2014
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis||Drug: Prednisolone Drug: dipyridamole Drug: Prednisone Drug: Z102 Other: placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||294 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Study Start Date :||June 2011|
|Actual Primary Completion Date :||August 2012|
|Actual Study Completion Date :||September 2012|
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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01369745
|United States, Ohio|
|Zalicus Investigational Site|
|Toledo, Ohio, United States, 43606|
|Study Director:||Margaret Lee, PhD||Zalicus, Inc.|