AI-guided precision immunotherapy for rheumatoid arthritis

An Artificial Intelligence-powered Approach to Precision Immunotherapy of Human Arthritis - A Double-blind, Randomized, Placebo-controlled Clinical Trial

This trial will see if adding the dnaJP1 peptide to hydroxychloroquine helps adults with moderately to severely active rheumatoid arthritis who have not used DMARDs or biologic treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 124 (estimated)
• Ages: 21 Years and up
• Sex: All
• Sponsor: Singapore Health Services (Academic / other)
• Drugs / interventions: rituximab, infliximab, tocilizumab, adalimumab, methotrexate, Prednisone
• Locations: 1 site (Singapore)
• Trial ID: NCT07013110 on ClinicalTrials.gov

What this trial studies

This is a phase 2, multicenter, randomized, double-blind, placebo-controlled outpatient trial enrolling 124 patients in a 1:1 allocation to receive either the dnaJP1 peptide plus hydroxychloroquine or placebo plus hydroxychloroquine. The protocol combines clinical outcome measures with molecular and immune profiling to identify mechanisms of induced immune tolerance and to discover biomarkers predictive of response. An AI-powered analytic approach will be used to integrate complex immunologic and clinical data for precision immunotherapy insights. Eligible participants are adults (≥21) with moderately to severely active RA (DAS28-ESR > 3.2) who are naive to conventional synthetic, biologic, and targeted synthetic DMARDs.

Who should consider this trial

Good fit: Adults aged 21 or older with moderately to severely active RA (DAS28-ESR > 3.2) who have not previously used cs-, b-, or ts-DMARDs and can attend scheduled outpatient visits are ideal candidates.

Not a fit: People who have already received DMARDs or biologic therapies, have low disease activity, or cannot attend in-person visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the combination could promote immune tolerance and improve symptoms while moving treatment away from broad immune suppression toward more targeted therapy.

How similar studies have performed: Tolerance-inducing peptide approaches are an emerging and largely early-stage field with limited prior human proof-of-concept, so this trial represents a relatively novel clinical application.

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

Where this trial is running

Singapore

• Singapore General Hospital — Singapore, Singapore (Recruiting)

Study contacts

• Principal investigator: Salvatore Albani, MD PhD — Singapore Health Services
• Study coordinator: Salvatore Albani, MD PhD

Conditions Rheumatoid Arthritis; Rheumatology; dnaJP1; Immune Tolerance