Efficacy and Safety of Oral AP1189 in Patients with Polymyalgia Rheumatica in Glucocorticoid Remission: A Phase II Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2026-525343-33-00
- Protocol
- SynAct-CS010
- Sponsor
- Synact Pharma ApS
Trial statistics
Diseases & Conditions
Objectives
The primary objectives of this study are to evaluate the efficacy and safety of 100 mg/day of oral resomelagon in patients diagnosed with polymyalgia rheumatica who are currently in remission on glucocorticoids. The evaluation is conducted over a 12-week treatment period. The secondary objective is to investigate the effect of the study drug compared to a placebo by assessing the proportion of patients achieving glucocorticoid-free remission.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with polymyalgia rheumatica. Eligible participants are aged 50 years or older and must fulfill the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria. Required medical history includes the initiation of glucocorticoid treatment at diagnosis four weeks prior to baseline. Inclusion requires the absence of giant cell arteritis as confirmed by vascular ultrasound at diagnosis or screening. Participants must demonstrate clinical remission at baseline, characterized by a lack of disease activity and a C-reactive protein level below 8.0 mg/l. The study objectives are:
- To explore the safety and tolerability of oral AP1189 tablets.
- To explore the efficacy of oral 100 mg/day AP1189 tablets over a 12-week treatment period.
Plans and Procedures
This phase II, multicentre, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of resomelagon (AP1189) in patients diagnosed with polymyalgia rheumatica who are in remission on glucocorticoid therapy. Following a screening visit to assess eligibility, participants are randomized to receive either 100 mg/day of AP1189 tablets or placebo administered via oral use. The treatment period lasts for 12 weeks, during which safety and tolerability are monitored through adverse event tracking, physical examinations, vital sign measurements, and clinical laboratory testing. Secondary objectives include assessing the proportion of patients achieving glucocorticoid-free remission, accumulated dosage, and changes in PMR activity score, patient global VAS, SF-36 components, and HAQ-DI at weeks 4, 8, and 12. The study involves a 12-week treatment duration.
Treatment
The experimental treatment consists of resomelagon administered as an AP1189 tablet. The dosage is 100 mg, provided via oral administration once daily for a duration of 12 weeks. This study is conducted in patients diagnosed with polymyalgia rheumatica who are currently in remission on glucocorticoids.
The control group receives a placebo tablet. The placebo is designed to be identical to the AP1189 tablet, with the exception of the active granulate.
Efficacy
The efficacy of oral 100 mg/day AP1189 in patients with polymyalgia rheumatica is evaluated through several parameters. The proportion of patients achieving glucocorticoid free remission at week 12 is assessed. Additional secondary endpoints include the accumulated glucocorticoid dosage from baseline to week 12 and the time to first relapse from baseline to week 12. Remission is defined by a PMR activity score (PMR-AS) of less than 10.
Changes from baseline are measured at weeks 4, 8, and 12 for several clinical indicators:
- PMR activity score
- Patient global VAS
- SF-36 MCS
- SF-36 PCS
- HAQ-DI
- Patient reported PMR VAS
- Patient reported global VAS
- Patient reported fatigue VAS
- Patient reported morning stiffness VAS
- Patient reported duration of morning stiffness
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated informed consent obtained before undergoing any trial-specific procedure. 2. Male or female aged ≥50 years. 3. Patients diagnosed with PMR fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. 4. Treatment with glucocorticoid for PMR initiated at diagnosis 4 weeks beforefore baseline. 5. Patients in clinical remission at baseline, defined as absence of PMR activity evaluated by the investigator based on symptoms and clinical examination combined with a CRP level be-low 8.0 mg/l. 6. No Giant cell arteritis (GCA) on vascular ultrasound at diagnosis or screening. 7. Patients with C-Reactive Protein (CRP) ≥8 mg/L at the time of diagnosis. 8. Willing and able to comply with the scheduled study visits, the treatment plan, and all study procedures. 9. Females of childbearing potential must have a negative pregnancy test at screening and again at baseline. 10. Sexually active female patients of childbearing potential and male patients 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 remain abstinent during the study and for 90 days after the last dose.
Exclusion Criteria
- Previous treatment with glucocorticoids for GCA. 2. Ongoing treatment with oral/intravenous/intramuscular glucocorticoids for other diseases than PMR. 3. Other inflammatory rheumatic diseases (e.g., rheumatoid arthritis, polymyositis, spondyloar-thritis, psoriatic arthritis, gout). 4. Symptoms or findings of GCA (newly onset-headache, tenderness of the temporal artery, jaw claudication, vision disturbances, limb claudication). 5. Non-inflammatory type of musculoskeletal condition (e.g., osteoarthritis or fibromyalgia) that in the Investigator's opinion is symptomatic and severe enough to interfere with the subject's primary diagnosis of PMR or the evaluation of the effect of the study drug. 6. Gastrointestinal diseases that, in the opinion of the Investigator, may interfere with the absorption or excretion of medications. 7. Severe, progressive, or uncontrolled renal (including CKD stage 4 or higher), hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease. 8. 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 5 years preceding the Screening Visit. 9. 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. 10. Females who are pregnant or lactating. 11. Participation in any other study involving investigational drug(s) within 4 weeks prior to study entry.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Yet Recruiting | 02 Feb 2026 | 60 |
Sites & Investigators
Research sites
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Apart from the AP1189 granulate, the placebo tablet and AP1189 tablet are identical. | Placebo | N/A | — | — | — | N/A |
AP1189 Tablet | Test | TABLET | ORAL USE | 100 | 12 | PRD11481319 |