A Study of the Safety, Tolerability and Efficacy of Treatment With AP1189 in Early RA Patients With Active Joint Disease (SynAct-CS002)

A Double-blind, Multicenter, Two-part, Randomized, Placebo-controlled Study of the Safety, Tolerability, and Efficacy of 4 Weeks Treatment With AP1189 in Early Rheumatoid Arthritis (RA) Patients With Active Joint Disease

This is a multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) > 22, who are to start up-titration with methotrexate.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: 50 mg AP1189; Drug: AP1189; Drug: Placebo

Detailed Description

A multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) > 22, who are to start up-titration with methotrexate.

The study will be conducted in two parts separated by an interim analysis.

Part 1: The subjects will be randomized in a 1:1:1 ratio into: .

• AP1189 dose 50 mg
• AP1189 dose 100 mg
• placebo

INTERIM ANALYSIS

Part 2: All subjects will be randomized into either design 1, 2 or 3 based on data from the interim analysis.

• Design 1: AP1189 dose 50 mg or placebo in a 2:1 ratio
• Design 2: AP1189 dose 100 mg or placebo in a 2:1 ratio
• Design 3: Continue with the same doses as in Part 1

The purpose of this study is to determine the safety and efficacy of 2 doses of AP1189 compared with placebo after 4 weeks of treatment.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus Universitetshospital
• Norway
  • Oslo, Norway, 0370
    • Diakonhjemmet sykehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent has been obtained prior to initiating any study specific procedures
• Male and female subjects, 18 to 85 years of age
• Confirmed diagnosis of (RA) Rheumatoid Arthritis according to the 2010 ACR/EULAR RA classification criteria
• Polyarthritis with joint swelling and tenderness of a minimum of three joints out of 68 joints tested
• Candidate for Methotrexate treatment
• Is about to begin treatment with MTX (Methotrexate)
• Tested positive for anti-CCP Anti-cyclic citrullinated peptide) or RF (Rheumatoid Factor)
• Severe active RA (CDAI > 22) at screening and baseline
• Negative QFG-IT (QuantiFERON-in-Tube test)
• Subjects should be able to complete the PRO (Patient Reported Outcome) questionnaires
• Females of child-bearing potential may only participate if using reliable means of contraception or are post-menopausal. Surgically sterilized women at least 6 months prior to screening
• Females of childbearing potential must have a negative pregnancy test at screening and baseline

Exclusion Criteria:

• Participation in any other study involving investigational drug(s) within 4 weeks prior to study entry
• Major surgery within 8 weeks prior to screening or planned surgery within 1 month following randomization
• Rheumatic autoimmune disease other than RA, including SLE (systemic Lupus Erythematosus), MCTD (Mixed Connective Tissue Disease), scleroderma, polymyositis, or significant systemic involvement secondary to RA. Sjögren syndrome with RA is allowable
• 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 within 2 weeks prior to dosing with the IMP (Investigational Medicinal Product)
• Corticosteroids are prohibited within 2 weeks prior to screening (and during the entire treatment period and until the final visit
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease
• Have prior renal transplant, current renal dialysis or severe renal insufficiency (determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault Formula of ≤30 mL/min/1,73 m2 calculated by the local lab)
• 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
• Pregnant women or nursing mothers
• History of alcohol, drug, or chemical abuse within the 6 months prior to screening
• Neuropathies or other painful conditions that might interfere with pain evaluation
• Body weight of >150 kg

Exclusion criteria that only applies for Norway

• Evidence of moderate and/or severe organ dysfunction
• Abnormal chest x-ray (as per the discretion of the investigator
• Evidence of positive hepatitis serology
• Evidence of peptic ulcer disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 mg AP1189; 50 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water.	Drug: 50 mg AP1189; 50 mg AP1189 powder in bottle; Other Names: AP1189
Experimental: 100 mg AP1189; 100 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water.	Drug: AP1189; 100 mg AP1189 powder in bottle
Placebo Comparator: Placebo; Placebo. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension i e. the powder will be added 50 ml water.	Drug: Placebo; Placebo powder in bottle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CDAI	The change in CDAI score from severe (CDAI > 22) to moderate (CDAI <= 22) after 4 weeks treatment compared to baseline.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Swollen and tender joints	Proportion of subjects achieving a reduction of more than 10 swollen and/or tender joints compared to baseline	4 weeks
CDAI score	Proportion of subjects achieving a change in CDAI score compared to baseline	4 weeks
DAS28 score	Proportion of subjects achieving a change in DAS28 compared to baseline	4 weeks
HAQ-DI (Health Assessment Questionnaire-Disability Index) questionnaire	Proportion of subjects achieving a change in HAQ-DI	4 weeks
FACIT-Fatigue questionnaire	Proportion of subjects achieving a change in FACIT-Fatigue	4 weeks
ACR (American College of Rheumatology) response	Proportion of subjects achieving a response assessed by ACR20, ACR50 and ACR70	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of AP1189 as measured on the following biomarkers: CXCL13, IL-1β, IL-6, IL-10, and TNF-α	Effect of AP1189, compared to placebo and by treatment group on inflammatory and collagen destructive biomarkers	4 weeks

Collaborators and Investigators

• Sponsor: SynAct Pharma Aps
• Investigators: Principal Investigator: Ellen-Margrethe Hauge, Professor, Aarhus Universitetshospital; Principal Investigator: Espen A Haavardsholm, Concultant, PhD, Diakonhjemmet Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2019
• Primary Completion (Actual): November 16, 2021
• Study Completion (Actual): November 16, 2021

Study Registration Dates

• First Submitted: June 26, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2021
• Last Update Submitted That Met QC Criteria: November 26, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Joint Diseases
• Other Study ID Numbers: SynAct-CS002

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