An Artificial Intelligence-powered Approach to Precision Immunotherapy of Human Arthritis

NCT ID: NCT07013110

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-18
• Study Completion Date: 2028-11-30

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).

Conditions

Rheumatoid Arthritis (RA); Rheumatology

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

dnaJP1

dnaJP1 peptide 25mg with Hydroxychloroquine (HCQ) 200mg once daily are administered orally, preferably in the morning on an empty stomach.

Group Type: EXPERIMENTAL

dnaJP1

Intervention Type: DRUG

The study drug is dnaJP1 peptide. It is a manmade short protein that can be taken easily as a pill. dnaJP1 works to restore the body's immune tolerance by improving its ability to self-adjust - helps to restore the immune system and improve controls on inflammation that has been lost.

Control

Placebo 25mg with Hydroxychloroquine (HCQ) 200mg once daily are administered orally, preferably in the morning on an empty stomach.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

This is the control.

Interventions

dnaJP1

The study drug is dnaJP1 peptide. It is a manmade short protein that can be taken easily as a pill. dnaJP1 works to restore the body's immune tolerance by improving its ability to self-adjust - helps to restore the immune system and improve controls on inflammation that has been lost.

Intervention Type: DRUG

Placebo

This is the control.

Intervention Type: DRUG

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Singapore General Hospital

OTHER

Sponsor Role: collaborator

Prof Salvatore Albani

OTHER

Sponsor Role: lead

Responsible Party

Prof Salvatore Albani

Director, SingHealth Translational Immunology and Inflammation Centre (STIIC)

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Salvatore Albani, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Singapore Health Services

Locations

Singapore General Hospital

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

Salvatore Albani, MD PhD

Role: CONTACT

salvo@duke-nus.edu.sg

+65 6576 7179

Grace Compton-Tan

Role: CONTACT

+65 6576 7185

Facility Contacts

Chin Teck NG, MD

Role: primary

ng.chin.teck@singhealth.com.sg

+65 6321 4028

Other Identifiers

dnaJP1

Identifier Type: -

Identifier Source: org_study_id