A Dose Response Study to Evaluate the Efficacy and Safety of Oral AP1189 Administered in Disease-Modifying Anti-Rheumatic Drug (DMARD) naïve Participants Participants With Early Rheumatoid Arthritis

NCT06671054 | Recruiting Phase 2 FDA Drug

• 1 other identifier: SynAct-CS008
• Study Type: interventional
• Target: 240
• Locations: 5 countries
• Sites: 11

Brief Summary

The study is a randomized, double blind, placebo-controlled, dose response, phase II, multicentre trial to evaluate the efficacy and safety of oral AP1189 administered at the doses of 40, 70, or 100 mg for 12 weeks in combination with methotrexate, in DMARD-naïve participants with early rheumatoid arthritis and active inflammation.

Conditions

Rheumatoid Arthritis (RA)

Outcome Measures

Primary Outcomes (1)

• Change in Disease Activity Score 28 (DAS28)-C-Reactive Protein (CRP)

  Absolute change from baseline in DAS28-CRP at Week 12

  Week 12

Study Arms (4)

AP1189 40 mg

EXPERIMENTAL

12 weeks daily treatment of oral AP1189 40 mg as add-on to Methotrexate (MTX)

Drug: AP1189, 40 mg

AP1189 70 mg

EXPERIMENTAL

12 weeks daily treatment of oral AP1189 70 mg as add-on to Methotrexate (MTX)

Drug: AP1189, 70 mg

AP1189 100 mg

EXPERIMENTAL

12 weeks daily treatment of oral AP1189 100 mg as add-on to Methotrexate (MTX)

Drug: AP1189, 100 mg

Placebo

EXPERIMENTAL

12 weeks daily treatment of oral AP1189 matching placebo as add-on to Methotrexate (MTX)

Drug: AP1189 matching placebo

Interventions

AP1189, 40 mg DRUG

AP1189 tablets for oral use

AP1189 40 mg

AP1189, 70 mg DRUG

AP1189 tablets for oral use

AP1189 70 mg

AP1189, 100 mg DRUG

AP1189 tablets for oral use

AP1189 100 mg

AP1189 matching placebo DRUG

AP1189 tablets for oral use

Placebo

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent obtained before undergoing any trial-specific procedure.
• Participants with definite RA diagnosis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
• Disease duration no longer than 6 months from diagnosis at the time of Baseline Visit and with a history of RA symptoms which does not exceed 18 months.
• Participants must be naïve to any Disease-modifying anti-rheumatic drugs (DMARDs)
• Participants with at least 6/68 tender and 6/66 swollen joints at Screening Visit and Baseline.
• Participants with "high" disease activity as documented by a Disease Activity Score 28 (DAS28) (C-Reactive Protein - CRP) index score \> 5.1 at screening, and Clinical disease activity index (CDAI) \>22 at Screening Visit and Baseline.
• Participants with serum high sensitive C-Reactive Protein (hsCRP) ≥3 mg/L at the time of screening.
• Participants positive for serum rheumatoid factor (RF), AND/OR anti-cyclic citrullinated peptide antibodies (anti-CCP). If seronegative RA, hsCRP ≥6 mg/L at the time of screening.
• Willing and able to comply with the scheduled study visits, the treatment plan, and all study procedures.
• Females of childbearing potential must have a negative pregnancy test at screening and again at baseline.
• Sexually active female participants of childbearing potential and male participants are excluded if not practicing two different methods of birth control with their partner during the study and for 90 days after the last dose of study drug or who will not remain abstinent during the study and for 90 days after the last dose.

You may not qualify if:

• Functional class IV of Global Functional Status in RA, as defined by the ACR Classification.
• Rheumatic autoimmune disease other than RA, i.e. systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA.
• Current inflammatory joint disease other than RA.
• Non-inflammatory type of musculoskeletal condition that in the Investigator's opinion is symptomatic and/or severe enough to interfere with the subject's primary diagnosis of RA or the evaluation of the effect of the study drug.
• Gastrointestinal diseases known to interfere with the absorption or excretion of medications.
• Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
• Malignancy active during the 12 months preceding the Screening Visit.
• Acute hepatitis, chronic hepatitis, or detection of any unexplained elevation of serum ALT or AST greater than 1.5-fold ULN, at least twice in the 6 months before the Screening Visit) or HIV infection.
• History of alcohol or drug abuse during the 12 months preceding the Screening Visit.
• Vaccination with live vaccines during the 6 weeks preceding the Screening Visit.
• Haemoglobin \<9 g/dL or Haematocrit \<30% at the Screening Visit
• White blood cell (WBC) count \<3.0 x 109/L at the Screening Visit.
• Absolute neutrophil count \<1.2 x 109/L at the Screening Visit.
• Platelet count \<100 x 109/L at the Screening Visit.
• Serum alkaline-phosphatase, or gamma-glutamyl-transferase greater than 3-fold ULN; alanine aminotransferase, or aspartate aminotransferase, or total bilirubin greater than 2-fold ULN At the Screening Visit.

Sponsors & Collaborators

• SynAct Pharma Aps: lead
• NBCD A/S: collaborator

Study Sites (11)

Nouvelle Clinical Research LLC

Cutler Bay, Florida, 33189, United States

RECRUITING

Millennium Medical Research LLC

Miami, Florida, 33126, United States

RECRUITING

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

RECRUITING

Diagnostic Consultative Center Aleksandrovska

Sofia, 1431, Bulgaria

RECRUITING

Medical Center Tera Medico

Vratsa, 3000, Bulgaria

RECRUITING

Sanos Clinic Herlev

Herlev, 2730, Denmark

RECRUITING

IMSP Spitalul Clinic Municipal "Sfanta Treime"

Chisinau, 2068, Moldova

RECRUITING

M2Mmed

Chorzów, 41-500, Poland

RECRUITING

Vita Longa Sp. z o. o.

Katowice, 41-500, Poland

RECRUITING

Medyczne Centrum Hetmańska

Poznan, 60-218, Poland

RECRUITING

DC-MED Michal Kowalski S.K.

Swidnica, 58-100, Poland

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

N-(3-(1-(2-nitrophenyl)-1H-pyrrol-2-yl)allylidenamino)guanidine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Thomas Jonassen, MD

CONTACT

+45 4015 6669; tj@synactpharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 4, 2024
• Study Start: October 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: October 6, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1); US (3); DK (1); BU (2); PL (4)