Rheumatoid arthritis, ulcerative colitis and Sjögren’s syndrome Other
Conditions
Interventions
Patients will receive the trial drug JNJ-67484703 at either a low (0.5mg/kg) or high (3mg/kg) dose. Each patient will receive the trial drug at weeks 0, 1 and 2 and then every 2 weeks until week 10. T
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
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
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 mucosal dysplasia. 31. Presence on screening endoscopy of adenomatous colonic polyps, if not removed before trial entry, or history of adenomatous colonic polyps that were not removed 32. Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn’s disease or clinical findings suggestive of Crohn’s disease Exclusion criteria for patients with Sjögren’s syndrome: 33. Diagnosis of any other non-SjS sicca syndrome 34. DMARD or other immunosuppressive therapy with the exception of methotrexate,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The biological effects of multiple doses of JNJ-67484703 in disease-relevant tissues (synovium, gut, salivary gland) over time in participants with RA, UC and SjS, measured using cellular analysis techniques at weeks 0, 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability measured using NCI-CTCAE criterion Version 5 at weeks 0, 1, 2, 4, 6, 8, 10, 12, 16, and 24 2. Disease-relevant immune cell populations measured using cellular analysis techniques at weeks 0, 6, 12, 24 3. Inflammation in target tissue measured using Krenn scoring (RA), Focus score, mean foci area, the percentage area of infiltration, T/B cell organisation and presence of germinal centre-like structures (SjS), Robarts Histopathology Index (RHI) and Nancy Index at weeks 0 and 12 4. Markers of inflammation in peripheral blood measured using immunoassays at weeks 0, 6, 12, and 24 5. Autoantibody levels measured using immunoassays at weeks 0, 6, 12, and 24 6. Clinical measures of disease activity: 6.1. Overall disease activity in RA as measured by: 6.1.1. Disease Activity Score 28 using C-reactive protein (DAS28-CRP) at weeks 0, 6, 12, and 24 6.1.2. Physician global visual analogue scale (VAS) weeks 0, 6, 12, and 24 6.1.3 Response to treatment in RA as measured by: 6.1.3.1. European Alliance of Associations for Rheumatology (EULAR) response weeks 0, 6, 12, and 24 6.1.3.2. Proportion of participants in DAS28-CRP remission (<2.6) and low disease activity (=3.2) states weeks 0, 6, 12, and 24 6.2. Overall disease activity in SjS as measured by: 6.2.1. Physician global VAS at weeks 0, 6, 12, and 24 6.2.2. Response to treatment in SjS as measured by Composite of Relevant Endpoints for SjS (CRESS) responders (ultrasound excluded) 6.2.3. Salivary flow in SjS as measured by Unstimulated salivary flow (ml/min; assuming 1g˜1ml) at weeks 0, 6, 12, 24 6.2.4. Stimulated salivary flow (ml/min; assuming 1g˜1ml) at weeks 0, 6, 12, 24 6.2.5. Ocular involvement in SjS as measured by Schirmer’s test (mm) at weeks 0, 12 6.3. Overall disease activity in UC as measured by: 6.3.1. Mayo clinic score (MCS) at weeks 0, 12 6.3.2. Partial Mayo Clinic Score at weeks 0, 2, 4, 6, 8, 10, 16, 24 6.3.3. Simple Clinical Colitis Activity Index (SCCAI) at weeks 0, 2, 4, 6, 8, 10 | — |
Countries
England, United Kingdom
Contacts
Public ContactManpreet Wilkhu
Outcome results
None listed