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

NCT ID: NCT06671054

Last Updated: 2025-10-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-01

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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The purpose of the trial is to evaluate the efficacy, safety and tolerability of 12 weeks daily treatment of oral AP1189 at the doses of 40, 70, or 100 mg in combination with oral MTX compared to oral MTX alone.

The aim is to have 240 participants randomized to one of the 4 treatment groups, in a 1:1:1:1 ratio and treated with both AP1189/Placebo and MTX.

Conditions

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Rheumatoid Arthritis (RA)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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AP1189 40 mg

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

Group Type EXPERIMENTAL

AP1189, 40 mg

Intervention Type DRUG

AP1189 tablets for oral use

AP1189 70 mg

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

Group Type EXPERIMENTAL

AP1189, 70 mg

Intervention Type DRUG

AP1189 tablets for oral use

AP1189 100 mg

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

Group Type EXPERIMENTAL

AP1189, 100 mg

Intervention Type DRUG

AP1189 tablets for oral use

Placebo

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

Group Type EXPERIMENTAL

AP1189 matching placebo

Intervention Type DRUG

AP1189 tablets for oral use

Interventions

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AP1189, 40 mg

AP1189 tablets for oral use

Intervention Type DRUG

AP1189, 70 mg

AP1189 tablets for oral use

Intervention Type DRUG

AP1189, 100 mg

AP1189 tablets for oral use

Intervention Type DRUG

AP1189 matching placebo

AP1189 tablets for oral use

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* Estimated creatinine clearance less than 45 mL/min/1.73 m2 (MDRD) at the Screening Visit.
* 12-lead electrocardiogram (ECG) with abnormal clinically significant findings, as judged by the Investigator, at the Screening Visit.
* Positive QuantiFERON-in-Tube test (QFG-IT).
* Use of hydroxychloroquine during the 30 weeks preceding the Screening Visit.
* Treatment with any systemic or intraarticular corticosteroid within 6 weeks before the Screening Visit.
* Intermittent use of nonsteroidal anti-inflammatory drugs (NSAIDs). Use of NSAIDs is allowed if used in a stable dose regimen for at least 4 weeks prior to the Screening Visit.
* Use of other investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding the Screening Visit.
* Any other clinically relevant disease and condition that, in the opinion of the Investigator, may jeopardize efficacy or safety assessments or may compromise the subject's safety during trial participation.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NBCD A/S

INDUSTRY

Sponsor Role collaborator

SynAct Pharma Aps

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Nouvelle Clinical Research LLC

Cutler Bay, Florida, United States

Site Status RECRUITING

Millennium Medical Research LLC

Miami, Florida, United States

Site Status RECRUITING

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Site Status RECRUITING

Diagnostic Consultative Center Aleksandrovska

Sofia, , Bulgaria

Site Status RECRUITING

Medical Center Tera Medico

Vratsa, , Bulgaria

Site Status RECRUITING

Sanos Clinic Herlev

Herlev, , Denmark

Site Status RECRUITING

IMSP Spitalul Clinic Municipal "Sfanta Treime"

Chisinau, , Moldova

Site Status RECRUITING

M2Mmed

Chorzów, , Poland

Site Status RECRUITING

Vita Longa Sp. z o. o.

Katowice, , Poland

Site Status RECRUITING

Medyczne Centrum Hetmańska

Poznan, , Poland

Site Status RECRUITING

DC-MED Michal Kowalski S.K.

Swidnica, , Poland

Site Status RECRUITING

Countries

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United States Bulgaria Denmark Moldova Poland

Central Contacts

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Thomas Jonassen, MD

Role: CONTACT

+45 4015 6669

Facility Contacts

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Rawan Jumean, MD

Role: primary

Ramon Morada

Role: primary

Alan Kiwitz, MD

Role: primary

Role: backup

(814) 693-0300

Delina Ivanova, Dr.

Role: primary

Tanya Tsvetanova, Dr.

Role: primary

Mads Bakkegaard, MD

Role: primary

Svetlana Agachi, Ass. Prof.

Role: primary

Magdalena Włoch-Targońska, Dr.

Role: primary

Barbara Stasiuk, Dr.

Role: primary

Piotr Leszczyński, Dr.

Role: primary

Małgorzata Rajewska, Dr.

Role: primary

Role: backup

Other Identifiers

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SynAct-CS008

Identifier Type: -

Identifier Source: org_study_id

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