An Artificial Intelligence-powered Approach to Precision Immunotherapy of Human Arthritis - A Double-blind, Randomized, Placebo-controlled Clinical Trial
Trial ID: NCT07013110
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: PHASE2
Start date: 2025-06-18
Completion date: 2028-11
Sponsor: Prof Salvatore Albani
Collaborators: Singapore General Hospital
Conditions: Rheumatoid Arthritis (RA); Rheumatology
Interventions: dnaJP1; Placebo
Locations: Singapore General Hospital
Countries: Singapore
Enrollment: 124
Age range: 21 Years - None
Sex: ALL

Summary:
This clinical study is a multi-center, randomized, double-blind, placebo-controlled, outpatient study comparing the efficacy of combination of dnaJP1 peptide and hydroxychloroquine versus combination of placebo and hydroxychloroquine in patients with moderately to severely active RA who are naive to cs-, b-, tsp.-DMARDs.

A sample size of 124 patients will be enrolled in the study. Each patient will receive either combination of dnaJP1 peptide and hydroxychloroquine or combination of placebo and hydroxychloroquine in 1:1 allocation ratio.

Eligibility criteria:
Inclusion Criteria:

1. Diagnosis of rheumatoid arthritis (RA) based on 2010 ACR/EULAR classification criteria
2. DAS28-ESR score more than 3.2 (at least moderately active)
3. Male or female with age 21 or above
4. Ability to understand and sign informed consent
5. Agree to use acceptable methods of contraception for e.g. oral contraceptive pills, implanted contraception, barrier methods, and intra-uterine devices
6. Allowed used of oral Prednisone up to 10 mg/day and NSAIDs, as prescribed by the treating physician
7. Able and willing to comply with the protocol, including availability for all scheduled study visits and assessments.

Using the 2010 ACR/EULAR classification criteria for RA, classification as definite RA is based upon the presence of synovitis in at least one joint, the absence of an alternative diagnosis that better explains the synovitis, and the achievement of a total score of at least 6 (of a possible 10) from the individual scores in four domains. The highest score achieved in a given domain is used for this calculation. These domains and their values are:

1. Number and site of involved joints:

   * 2 to 10 large joints (from among shoulders, elbows, hips, knees, and ankles) = 1 point
   * 1 to 3 small joints (from among the metacarpophalangeal joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists) = 2 points
   * 4 to 10 small joints = 3 points
   * Greater than 10 joints (including at least 1 small joint) = 5 points
2. Serological abnormality (rheumatoid factor or anti-citrullinated peptide/protein antibody)

   * Low positive (above the upper limit of normal \[ULN\]) = 2 points
   * High positive (greater than three times the ULN) = 3 points
3. Elevated acute phase response (erythrocyte sedimentation rate \[ESR\] or C-reactive protein \[CRP\]) above the ULN = 1 point
4. Symptom duration at least six weeks = 1 point

Exclusion Criteria:

1. On prednisolone \>10 mg daily
2. History of receiving:

   * conventional synthetic (cs-) disease modifying anti-rheumatic drugs (DMARDs) such as sulfasalazine, methotrexate, and leflunomide administered 6 months prior to screening

     •. biological (b-) DMARDs such as rituximab, infliximab, tocilizumab, adalimumab, etc.
   * tissue-specific (tsp.-) DMARDs such as JAK inhibitors
3. History of lymphoma
4. Active malignancy requiring treatment the last 5 years except for non-melanoma skin cancers and carcinoma of the cervix in situ
5. Pregnancy
6. Breast-feeding
7. Active Infection, e.g., Hepatitis B, tuberculosis
8. A known hypersensitivity to dnaJP1 or to any of the excipients
9. Significant cardiac history, e.g., have experienced any of the following within 12 weeks of study entry: myocardial infarction, unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure
10. A history or presence of dermatological, cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, haematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking HCQ and/or the investigational product or could interfere with the interpretation of data
11. An eGFR based on the most recent available serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of \<40 ml/min/1.73 m2
12. A history of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the ULN or the most recent available total bilirubin 1.5 times the ULN

Outcomes:
To estimate effect size needed to ascertain the power i.e. the number of patients to be tested in the future study to prove superiority of the combination dnaJP1 and HCQ versus placebo and HCQ - To determine this ACR20 will be employed; A primary endpoint of the study will be to determine safety and tolerability of the experimental treatment in terms of AEs, SAEs, TEAEs; A mechanistic predictor of clinical efficacy at enrolment before first dosing related to immune changes in the cell activation; A mechanistic biomarker of treatment response based on 20% change from baseline in increase in Tregs and decrease in inflammatory T cells