Clinical trial NCT07013110: An Artificial Intelligence-powered Approach to Precision Immunotherapy of Human Arthritis
Official title: An Artificial Intelligence-powered Approach to Precision Immunotherapy of Human Arthritis - A Double-blind, Randomized, Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rheumatoid Arthritis (RA)
Rheumatology
Keywords: Rheumatoid Arthritis
Rheumatology
dnaJP1
Immune Tolerance
Lead sponsor: Singapore Health Services
Sponsor class: OTHER
Collaborators: name: Singapore General Hospital
First posted: 2025-06-10
Enrollment: 124
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Despite the availability of a plethora of new drugs to treat Rheumatoid Arthritis (RA), a holistic and accurate understanding of how therapy with biologics works is still missing. The knowledge gap is particularly poignant if one considers that the second-generation drugs developed for immune therapy is still entirely suppressive. Thus, the dramatic advances in molecular immunology has yet to be translated into the needed evolution from immune suppression to true immune tolerization, an important step on the evolutionary pathway from therapy to cure.

This study is designed to be a multi-center, randomized, double-blind, placebo-controlled trial which has two fundamental objectives:

To identify and dissect mechanisms of induction of immune tolerance in RA patients in response to immune therapy with dnaJP1, a microbiome-derived peptide. Tangibly in the context of clinical development, the investigators aim to capitalize on this knowledge to identify and validate biomarkers predictor of efficacy and clinical response;

The investigators will also determine the effect size needed to demonstrate whether the combination of dnaJP1 peptide and hydroxychloroquine (HCQ) is superior to the combination of placebo and hydroxychloroquine in the treatment of patients with moderately to severely active RA naïve to disease modifying anti-rheumatic drugs (i.e. DMARDs and biologics-naïve).

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. On conventional synthetic (cs-), biological (b-) or tissue-specific (tsp.-) disease modifying anti- rheumatic drugs (DMARDs), these include, but not limited to, methotrexate, leflunomide, cytokine inhibitors, kinase inhibitors, biologics interfering with CTLA4 and CD20 molecules
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

Primary outcomes:
measure: 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
timeFrame: At Study End being 7 Months
measure: A primary endpoint of the study will be to determine safety and tolerability of the experimental treatment in terms of AEs, SAEs, TEAEs
timeFrame: At Study End being 7 Months
measure: A mechanistic predictor of clinical efficacy at enrolment before first dosing related to immune changes in the cell activation
timeFrame: At Study End being 7 Months
measure: A mechanistic biomarker of treatment response based on 20% change from baseline in increase in Tregs and decrease in inflammatory T cells
timeFrame: At Study End being 7 Months
Secondary outcomes:
measure: To estimate the 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 - ACR50
timeFrame: At Study End being 7 Months
measure: To estimate the 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 - ACR70
timeFrame: At Study End being 7 Months
measure: To estimate the 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 - DAS28-ESR
timeFrame: At Study End being 7 Months
measure: To estimate the 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 - DAS28-hsCRP
timeFrame: At Study End being 7 Months
measure: To estimate the 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 - Clinical Disease Activity Index (CDAI) Score
timeFrame: At Study End being 7 Months
measure: To estimate the 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 - Simplified Disease Activity Index (SDAI)
timeFrame: At Study End being 7 Months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
Study officials:
affiliation: Singapore Health Services
name: Salvatore Albani, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: