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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Synact Pharma ApS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

5 Dec 2024 → 12 May 2026

Decision date (initial)

2024-11-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine the efficacy of oral AP1189 in combination with oral Methotrexate (MTX) over a 12-week treatment period in Disease-Modifying Anti-Rheumatic Drug (DMARD)-naïve participants with newly diagnosed Rheumatoid Arthritis (RA), in comparison with oral MTX alone.

Secondary objectives 1

1. To determine the safety and tolerability of oral AP1189 in combination with oral MTX, in comparison with oral MTX alone

Conditions and MedDRA coding

Rheumatoid Arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Signed and dated informed consent obtained before undergoing any trial-specific procedure
2. Male or female aged ≥18 years
3. Participants with definite RA diagnosis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria
4. Disease duration no longer than 6 months from diagnosis at the time of Baseline Visit (newly diagnosed) and with a history of RA symptoms which does not exceed 18 months. RA symptoms is defined as the participant self-reported duration of signs and symptoms of synovitis (e.g. pain, swelling, tenderness) of any joints
5. Participants must be naïve to any DMARDs (csDMARDs, or bDMARDs, or tsDMARDs)
6. Participants with at least 6/68 tender and 6/66 swollen joints at Screening Visit and Baseline.
7. 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
8. Participants with serum high sensitive C-Reactive Protein (hsCRP) ≥3 mg/L at the time of screening
9. 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
10. Willing and able to comply with the scheduled study visits, the treatment plan, and all study procedures
11. Females of childbearing potential must have a negative pregnancy test at screening and again at baseline
12. Sexually active female participants of childbearing potential and male participants must use a highly effective method of birth control (hormonal contraceptives, intrauterine device, vasectomy, bilateral tubal occlusion, sexual abstinence) 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. (See Appendix 1: Contraceptive Guidance and Woman of Childbearing Potential)

Exclusion criteria 24

1. Functional class IV of Global Functional Status in RA, as defined by the ACR Classification
2. Vaccination with live vaccines during the 6 weeks preceding the Screening Visit
3. Haemoglobin <9 g/dL or Haematocrit <30% at the Screening Visit
4. White blood cell (WBC) count <3.0 x 109/L at the Screening Visit
5. Absolute neutrophil count <1.2 x 109/L at the Screening Visit.
6. Platelet count <100 x 109/L at the Screening Visit
7. 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
8. Estimated creatinine clearance less than 45 mL/min/1.73 m2 (CKD-EPI) at the Screening Visit
9. 12-lead electrocardiogram (ECG) with abnormal clinically significant findings, as judged by the Investigator, at the Screening Visit
10. Positive or indeterminate QuantiFERON-in-Tube test (QFG-IT) (Mantoux test can be used if QFG-IT is not possible)
11. Use of hydroxychloroquine during the 30 weeks preceding the Screening Visit
12. Rheumatic autoimmune disease other than RA, i.e. systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome)
13. Treatment with any systemic or intraarticular corticosteroid within 6 weeks before the Screening Visit (topical or inhaled corticosteroids are allowed)
14. 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
15. Use of other investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding the Screening Visit
16. 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
17. Current inflammatory joint disease other than RA
18. Non-inflammatory type of musculoskeletal condition (e.g., osteoarthritis or fibromyalgia) 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
19. Gastrointestinal diseases known to interfere with the absorption or excretion of medications
20. Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease
21. Malignancy (with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ) active during the 12 months preceding the Screening Visit
22. Acute hepatitis (during the 6 months preceding the Screening Visit), chronic hepatitis (previous documented diagnosis of viral or autoimmune 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
23. History of alcohol or drug abuse during the 12 months preceding the Screening Visit
24. Females who are pregnant, lactating.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline in DAS28(CRP) after 12 weeks of combined treatment with AP1189/Placebo and MTX

Secondary endpoints 12

1. ACR20 responder rate at Week 12
2. ACR50 responder rate at Week 12
3. ACR70 responder rate at Week 12
4. Change from baseline of the 7 individual components of the ACR criteria (tender/painful joint count, swollen joint count, Patient’s assessment of arthritis pain, Patient Global Assessment of arthritis (PtGA), Physician Global Assessment of arthritis (PhGA), HAQ-DI, serum CRP) at each time point
5. Change from baseline in DAS28 at each time point
6. Proportion of participants with Low, Moderate, or High Disease Activity based on DAS28 at each time point
7. Proportion of participants fulfilling DAS28 remission criteria at each time point (DAS28<2.6)
8. Proportion of participants achieving a Good EULAR response (a DAS28 score≤3.2 at the considered visit, together with an improvement from baseline in DAS28>1.2) at each time point
9. Change from baseline in SDAI and CDAI at each time point
10. Proportion of participants with Low, Moderate, or High Disease Activity based on SDAI and CDAI at each time point
11. Proportion of participants fulfilling the ACR/EULAR remission criteria at each time point
12. Proportion of participants achieving HAQ DI MCID (>0.22 reduction in HAQ DI from baseline)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Synact Pharma ApS

Sponsor organisation

Synact Pharma ApS

Address

Dronninggaards Alle 136

City

Holte

Postcode

2840

Country

Denmark

Scientific contact point

Organisation

Synact Pharma ApS

Contact name

Senior Director Medical Officer/ Medical Affairs

Public contact point

Organisation

Synact Pharma ApS

Contact name

Senior Director Medical Officer/ Medical Affairs

Third parties 4

Locations

5 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 59 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications