A trial to investigate the effects of multiple doses of JNJ-67484703 in patients with rheumatoid arthritis, ulcerative colitis and Sjögren’s syndrome

Phase 2

• Conditions: Rheumatoid arthritis, ulcerative colitis and Sjögren’s syndrome; Not Applicable

• Registration Number: ISRCTN31164692
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-09-28
• Last Update Posted: 10 April 2023
• Study Completion: 2024-03-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

Main inclusion criteria for all cohorts:
1. Informed consent must be obtained provided prior to any trial-related procedures being performed
2. Male and female participants aged =18 and =75 years at the time of enrolment
3. Able to communicate well with the investigator, and to understand and comply with the requirements of the trial
4. Willing to have repeat tissue biopsy relevant to disease group (ultrasound-guided synovial biopsy, minor salivary gland biopsy or endoscopic colonic mucosal biopsy)
5. Body weight within the range of 45.0 kg to 120.0 kg, inclusive

Inclusion criteria for patients with rheumatoid arthritis (RA):
6. Confirmed clinical diagnosis of RA
7. Active RA
8. Joint amenable to biopsy by ultrasound criteria
9. Autoantibody positive
10. Have methotrexate (MTX) inadequate response
11. If using regular non-steroidal anti-inflammatory drugs (NSAIDs) must be on a stable dose

Inclusion criteria for patients with ulcerative colitis (UC):
12. Confirmed clinical diagnosis of UC
13. Moderately to severely active UC on endoscopy
15. Either primary non-response or secondary loss of response to one or more biologic or targeted synthetic therapies
16. Medications/therapies must have been discontinued by the number of stated weeks before Visit 2 (Baseline) as outlined in the protocol.
17. A participant =45 years of age must have had a full colonoscopy. Adenomatous polyps must be removed before the first dose of trial intervention
18. A participant who has had extensive colitis for =8 years, or disease limited to the left side of the colon for =10 years, must have or have had a full colonoscopy to assess for the presence of dysplasia or malignancy at the Screening Visit

Inclusion criteria for patients with Sjögren’s syndrome (SjS):
19. A diagnosis of SjS, according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria
20. Autoantibody positive
21. At least low activity” in the biological domain of EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI)
22. ESSPRI component scores as outlined in the protocol
23. Residual stimulated whole salivary flow

Exclusion Criteria

Main exclusion criteria for all cohorts:
1. Prior B cell depletion
2. Other biologic therapy or targeted synthetic disease-modifying antirheumatic drugs (DMARDs)
3. Receipt of any investigational medicinal product within 16 weeks, or approximately 5 half-lives (whichever is longer) prior to Visit 2 (baseline)
4. Any active or ongoing viral, bacterial or other infections
5. Confirmed, suspected, or close contact with a person with known or suspected SARS-CoV-2 infection
6. Major organ, haematopoietic stem cell or bone marrow transplant
7. Any cancer within the previous 5 years,
8. Severe, uncontrolled fibromyalgia symptoms.
9. Treatment with glucocorticoids unless on a stable dose of prednisolone
10. Positive test for HIV, Hepatitis C Virus or Hepatitis B Virus
11. Active cytomegalovirus (CMV) or Epstein–Barr virus (EBV)
12. Live vaccine within 12 weeks of registration
13. Bacillus Calmette-Guérin (BCG) vaccination within 12 months prior to trial drug administration.
14. Evidence of active or latent tuberculosis (TB)
15. Has known allergies, hypersensitivity, or intolerance to JNJ-67484703 or its excipients
16. Any medical, surgical or psychiatric condition that the investigator believes may jeopardise the participant, or the validity of the trial results, were they to participate in the trial
17. Has experienced myocardial infarction, unstable ischaemic heart disease, or stroke within 12 weeks of Screening Visit
18. Female who is pregnant, breastfeeding, intends to become pregnant or is of childbearing potential, not willing to use highly effective contraceptive methods
19. A non-vasectomised male participant who refuses to wear a condom during the trial and for 14 weeks after the last dose of trial treatment when engaging in any activity that allows for passage of ejaculate to another person. An additional method of highly effective method of contraception must also be used.
20. A male participant must agree not to donate sperm for the purpose of reproduction during the trial and for a minimum 14 weeks after receiving the last dose of the trial intervention
21. Screening laboratory test results as specified in the protocol
22. Advised by clinician not to have a tissue biopsy due to clinical reasons or anti-coagulant use
23. Septic arthritis of a native or prosthetic joint in the last 12 months (or indefinitely if the prosthetic joint remains in situ)

Exclusion criteria for patients with rheumatoid arthritis:
24. History of or current inflammatory joint disease other than RA
25. Currently taking anticoagulant medications (not anti-platelet agents) that would contraindicate synovial biopsy
26. DMARD or other immunosuppressive therapy with the exception of methotrexate, sulfasalazine or hydroxychloroquine at stable doses

Exclusion criteria for patients with ulcerative colitis:
27. History of severe extensive colitis
28. Has UC limited to the rectum only
29. Presence or history of a fistula
30. History of colonic mucos

Study & Design

• Study Type: Interventional
• Study Design: Not specified