A Phase II Trial Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis

NCT01369745 | Completed Phase 2 Results DMC

• 1 other identifier: Z102-008
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 1

Brief Summary

Thus study will test an experimental drug called Z-102 (combination of prednisolone and dipyridamole) to treat patients with moderate to severe rheumatoid arthritis.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Moderate to severe

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in DAS28-CRP at 12 Weeks

  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.

  baseline to week 12

Secondary Outcomes (4)

• Change From Baseline in DAS28-CRP Individual Components at 12 Weeks

  Baseline to week 12

• Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks

  Week 12

• Multidimensional Assessment of Fatigue (MAF) at Week 12

  week 12

• Time to Failure (Days)

  Baseline to 12 weeks

Study Arms (5)

Prednisolone

ACTIVE COMPARATOR

Prednisolone 2.7 mg daily for 12 weeks

Drug: Prednisolone

dipyridamole

ACTIVE COMPARATOR

Dipyridamole 360 mg daily for 12 weeks

Drug: dipyridamole

prednisone

ACTIVE COMPARATOR

Prednisone 5 mg daily for 12 weeks

Drug: Prednisone

Z102 (2.7/360)

EXPERIMENTAL

Prednisolone 2.7 mg plus dipyridamole 360 mg daily for 12 weeks

Drug: Z102

placebo

PLACEBO COMPARATOR

Placebo daily for 12 weeks

Other: placebo

Interventions

Prednisolone DRUG

Prednisolone 2.7 mg daily

Prednisolone

dipyridamole DRUG

dipyridamole 360 mg daily

dipyridamole

Prednisone DRUG

Prednisone 5 mg daily

prednisone

Z102 DRUG

Prednisolone 2.7 mg plus dipyridamole 360 mg daily

Also known as: prednisolone, dipyridamole

Z102 (2.7/360)

placebo OTHER

placebo

Eligibility Criteria

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

You may qualify if:

• Meet the ACR / EULAR criteria for classification of RA
• Have moderate to severe RA, defined as involving a minimum (≥6 total swollen and ≥6 total tender) of the 28 joints assessed
• Have screening CRP levels of at least 0.6 mg/dl and a DAS28-CRP score ≥4.5
• Have been on a stable dose of conventional DMARD therapy for at least 90 days without dosage adjustment or modification and should be able to maintain the same dose of conventional DMARD therapy during study participation (with or without glucocorticoid therapy

You may not qualify if:

• Treatment-refractory patients are excluded
• Has active cardiovascular disease, unless well controlled by appropriate treatment for a minimum of 3 months prior to screening
• Is taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325 mg
• Is currently taking steroids at a daily prednisone dose, or the equivalent, of \>10 mg
• Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering the study
• The need to continue the use of one or multiple NSAID's at the same time, or the use of acetaminophen on a chronic basis
• All opiate use is prohibited
• Use of any other medications or herbs used for the treatment of pain is prohibited
• Patients with a history of or currently active tuberculosis as per specific country guidelines are excluded
• Has uncontrolled diabetes mellitus as defined by a serum glucose \>126 mg/dl
• Knowingly has HIV infection or hepatitis
• Has undergone administration of any investigational drug within 30 days of study initiation
• All biologic agents are excluded for 90 days prior to Screening and throughout the study.
• Has undergone administration of rituximab or any B-cell depleting investigational drugs within 6 months of study initiation
• Has had a history of alcohol or drug abuse within the past 2 years

Sponsors & Collaborators

• Zalicus: lead

Study Sites (1)

Zalicus Investigational Site

Toledo, Ohio, 43606, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Prednisolone; Dipyridamole; Prednisone

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; Pregnadienediols

Limitations and Caveats

The study did not progress past the first stage of adaptive randomization. The number of subjects allocated to the dipyridamole 360 mg, prednisolone 2.7 mg, and prednisone 5 mg arms was insufficient to allow analysis of the secondary objectives.

Results Point of Contact

• Title: Margaret Lee,PhD
• Organization: Zalicus

mlee@zalicus.com

617-301-7142

Study Officials

• Margaret Lee, PhD

  Zalicus, Inc.

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2011
• First Posted: June 9, 2011
• Study Start: June 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: September 1, 2012
• Last Updated: May 15, 2014
• Results First Posted: April 30, 2014

Record last verified: 2014-04

Locations

US (1)