A Dose-range Study of the Safety and Efficacy of Treatment in Adult Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate (RESOLVE)

A Two-part, Randomized, Double-blind, Multi-center, Placebo-controlled Study of the Dose-range, Safety and Efficacy of 4 and 12 Weeks of Treatment With AP1189 in Adult Rheumatoid Arthritis (RA) Patients With an Inadequate Response to Methotrexate (MTX) Alone - (RESOLVE)

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: AP1189, 60 mg; Drug: AP1189, 80 mg; Drug: AP1189, 100 mg; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• Moldova, Republic of
  • Chișinău, Moldova, Republic of
    • Timofei Moșneaga Republican Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

• Must meet at least one of the following parameters at Screening:

  1. A positive result for Anti-Cyclic Citrullinated Peptide (anti-CCP) or Rheumatoid Factor (RF),
  2. Serum CRP ≥ 6 mg/L based on central laboratory value
• 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
• Subject has an inadequate clinical response to maximally tolerated methotrexate therapy
• 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
• Negative QuantiFERON-in-Tube test (QFG-IT)
• Females of child-bearing potential must use of highly effective birth control method
• Male participant's partner must use highly effective birth control

Exclusion Criteria:

• Use of all other biologic or nonbiologic DMARDs and immunosuppressive therapy within 4 weeks prior to administration of the first dose of study drug
• Oral steroids at a dose >10 mg/day of prednisone or a prescription for oral steroids which has changed within 4 weeks of baseline
• Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to baseline
• Major surgery (including joint operation) within 8 weeks prior to screening or planned surgery within the period of the study participation
• Rheumatic autoimmune disease other than RA
• Functional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedbound
• Prior history of or current inflammatory joint disease other than RA
• Subjects with fibromyalgia
• Initiation or change in dose for NSAIDs (including low-dose aspirin and Cyclooxygenase (COX-2) inhibitors) within 2 weeks prior to baseline
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease
• 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
• Have prior renal transplant, current renal dialysis, or moderate to severe renal insufficiency
• Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
• Evidence of active malignant disease (except basal cell carcinoma of the skin that has been excised and cured)
• History of alcohol, drug, or chemical abuse within the 6 months prior to screening
• Neuropathy or other painful, chronic conditions that might interfere with pain evaluation
• Body weight of >150 kg
• HBsAg positive and/or Anti-HBc with sign of current infection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Change in ACR20	The change in American College of Rheumatology 20% (ACR20) compared to baseline	4 weeks
Part B: Change in ACR20	The change in American College of Rheumatology 20% (ACR20) compared to baseline	12 weeks
Number of reported Adverse Events	Evaluation of the safety and tolerability of AP1189 on the number and severity of reported Adverse Events, compared with placebo	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Change in ACR50	The change in American College of Rheumatology 50% (ACR50) compared to baseline	4 weeks
Part B: Change in ACR50	The change in American College of Rheumatology 50% (ACR50) compared to baseline	12 weeks
Part A: Change in ACR70	The change in American College of Rheumatology 70% (ACR70) compared to baseline	4 weeks
Part B: Change in ACR70	The change in American College of Rheumatology 70% (ACR70) compared to baseline	12 weeks
Part A: Change in CDAI	The change Clinical Disease Activity Index (CDAI) compared to baseline	4 weeks
Part B: Change in CDAI	The change Clinical Disease Activity Index (CDAI) compared to baseline	12 weeks
Part A: Change in DAS-28	The change in Disease Activity Score (DAS-28), based on a C-Reactive Protein (CRP) value, compare to baseline	4 weeks
Part B: Change in DAS-28	The change in Disease Activity Score (DAS-28), based on a C-Reactive Protein (CRP) value, compare to baseline	12 weeks

Collaborators and Investigators

• Sponsor: SynAct Pharma Aps
• Collaborators: NBCD A/S

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2022
• Primary Completion (Actual): August 28, 2023
• Study Completion (Actual): August 28, 2023

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): November 6, 2024
• Last Update Submitted That Met QC Criteria: November 4, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: SynAct-CS006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No