RESOLVE: A Dose-range Study of the Safety and Efficacy of Treatment in Adult Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate
Study Details
Study Description
Brief Summary
The RESOLVE study is a two-part, randomized, double-blind, multi-center, placebo-controlled study of the safety, dose-range finding confirmation, and efficacy of 4 (Part A) and 12 weeks (Part B) of treatment with AP1189 in adult RA patients with an inadequate response to MTX alone.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
In Part A approximately 120 randomized patients will be treated with either 60 mg AP1189, 80 mg AP1189, 100 mg AP1189 or placebo once daily for 4 weeks as add-on treatment to stable MTX treatment. Part A will conclude with an unblinded assessment for risk/benefit and a recommendation for dose selection for Part B.
In Part B patients will be randomized into groups of equal size evaluating 2-3 doses of AP1189 versus placebo. All doses will be administered once daily for 12 weeks as add-on treatment to stable MTX treatment. The proposed sample size per dose group/placebo group is 75 patients, by which the total study population of Part B may be either 225 or 300 patients, depending on the number of dose groups of AP1189 selected for evaluation based on Part A.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: AP1189, 60 mg Part A: (AP1189, 60 mg); Part B: (TBD) |
Drug: AP1189, 60 mg
AP1189 tablets for oral use
|
Experimental: AP1189, 80 mg Part A: (AP1189, 80 mg); Part B: (TBD) |
Drug: AP1189, 80 mg
AP1189 tablets for oral use
|
Experimental: AP1189, 100 mg Part A: (AP1189, 100 mg); Part B: (TBD) |
Drug: AP1189, 100 mg
AP1189 tablets for oral use
|
Placebo Comparator: Placebo Part A: (placebo); Part B: (placebo). |
Drug: Placebo
Matching placebo tablets for oral use
|
Outcome Measures
Primary Outcome Measures
- Part A: Change in ACR20 [4 weeks]
The change in American College of Rheumatology 20% (ACR20) compared to baseline
- Part B: Change in ACR20 [12 weeks]
The change in American College of Rheumatology 20% (ACR20) compared to baseline
- Number of reported Adverse Events [12 weeks]
Evaluation of the safety and tolerability of AP1189 on the number and severity of reported Adverse Events, compared with placebo
Secondary Outcome Measures
- Part A: Change in ACR50 [4 weeks]
The change in American College of Rheumatology 50% (ACR50) compared to baseline
- Part B: Change in ACR50 [12 weeks]
The change in American College of Rheumatology 50% (ACR50) compared to baseline
- Part A: Change in ACR70 [4 weeks]
The change in American College of Rheumatology 70% (ACR70) compared to baseline
- Part B: Change in ACR70 [12 weeks]
The change in American College of Rheumatology 70% (ACR70) compared to baseline
- Part A: Change in CDAI [4 weeks]
The change Clinical Disease Activity Index (CDAI) compared to baseline
- Part B: Change in CDAI [12 weeks]
The change Clinical Disease Activity Index (CDAI) compared to baseline
- Part A: Change in DAS-28 [4 weeks]
The change in Disease Activity Score (DAS-28), based on a C-Reactive Protein (CRP) value, compare to baseline
- Part B: Change in DAS-28 [12 weeks]
The change in Disease Activity Score (DAS-28), based on a C-Reactive Protein (CRP) value, compare to baseline
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Confirmed diagnosis of RA according to the 2010 ACR/EULAR RA classification criteria and are ACR class I-III
-
≥6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts)
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Must meet at least one of the following parameters at Screening:
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A positive result for Anti-Cyclic Citrullinated Peptide (anti-CCP) or Rheumatoid Factor (RF),
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Serum CRP ≥ 6 mg/L based on central laboratory value
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Ongoing methotrexate therapy ≥12 weeks in a stable dose of 7.5 to 25 mg/week for at least 4 weeks prior to the baseline visit
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Subject has an inadequate clinical response to maximally tolerated methotrexate therapy
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Subjects should be receiving an adequate and prescribed stable dose of folic acid (≥5 mg/week total dose or as per local clinical practice) which should be confirmed or initiated at screening and continued throughout the study
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Negative QuantiFERON-in-Tube test (QFG-IT)
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Females of child-bearing potential must use of highly effective birth control method
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Male participant's partner must use highly effective birth control
Exclusion Criteria:
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Use of all other biologic or nonbiologic DMARDs and immunosuppressive therapy within 4 weeks prior to administration of the first dose of study drug
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Oral steroids at a dose >10 mg/day of prednisone or a prescription for oral steroids which has changed within 4 weeks of baseline
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Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to baseline
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Major surgery (including joint operation) within 8 weeks prior to screening or planned surgery within the period of the study participation
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Rheumatic autoimmune disease other than RA
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Functional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedbound
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Prior history of or current inflammatory joint disease other than RA
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Subjects with fibromyalgia
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Initiation or change in dose for NSAIDs (including low-dose aspirin and Cyclooxygenase (COX-2) inhibitors) within 2 weeks prior to baseline
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Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease
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Serum Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than 1.5 x the upper limit of normal (ULN) and alkaline phosphatase (ALP) and/or bilirubin values above the ULN at the screening visit
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Have prior renal transplant, current renal dialysis, or moderate to severe renal insufficiency
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Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
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Evidence of active malignant disease (except basal cell carcinoma of the skin that has been excised and cured)
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History of alcohol, drug, or chemical abuse within the 6 months prior to screening
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Neuropathy or other painful, chronic conditions that might interfere with pain evaluation
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Body weight of >150 kg
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HBsAg positive and/or Anti-HBc with sign of current infection.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Timofei Mosneaga Republican Clinical Hospital | Chișinău | Moldova, Republic of |
Sponsors and Collaborators
- SynAct Pharma Aps
- NBCD A/S
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SynAct-CS006