Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis
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ClinicalTrials.gov Identifier: NCT06037811 |
Recruitment Status :
Not yet recruiting
First Posted : September 14, 2023
Last Update Posted : March 13, 2024
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Condition or disease | Intervention/treatment | Phase |
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Inflammatory Arthritis Immune-related Adverse Event | Drug: Adalimumab Drug: Prednisone | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 30 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Early Adalimumab Induction for Treatment of Steroid Dependent Immune Checkpoint Inhibitor Associated Inflammatory Arthritis: A Pragmatic Randomized Clinical Trial |
Estimated Study Start Date : | April 2024 |
Estimated Primary Completion Date : | November 2025 |
Estimated Study Completion Date : | November 2025 |
Arm | Intervention/treatment |
---|---|
Active Comparator: Standard of care group
Prednisone 10 mg daily for 2 weeks, then taper by 2.5 mg every 2 weeks until stopped.
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Drug: Prednisone
Prednisone as per standard of care. |
Active Comparator: Adalimumab group
Adalimumab 40 mg subcutaneous every 2 weeks for 6 doses (12 weeks) + Prednisone 10 mg daily for 2 weeks, tapering by 2.5 mg every 2 weeks until stopped. |
Drug: Adalimumab
Participants will be randomized 1:1 (non-blinded) to receive either adalimumab (40 mg subcutaneous every 2 weeks for 12 weeks) and prednisone vs prednisone alone. Addition of methotrexate (MTX) and/or hydroxychloroquine (HCQ) is permitted, as needed, at the discretion of the treating rheumatologist. No additional conventional synthetic, targeted synthetic or biologic DMARDs are permitted during the trial. Drug: Prednisone Prednisone as per standard of care. |
- percentage of participants on prednisone [ Time Frame: at 12 weeks ]Definition of success: Thirty percent fewer participants on prednisone in Group 2 vs Group 1.
- Cumulative prednisone dose [ Time Frame: at 12 weeks ]Definition of success: Thirty percent reduction in the cumulative dose of steroids in Group 2 compared to Group 1.
- percentage of participants on prednisone [ Time Frame: 24 weeks ]Definition of success: Thirty percent difference between the two groups
- Cumulative prednisone dose [ Time Frame: 24 weeks ]Definition of success: Thirty percent difference between the two groups
- percentage of dose reduction of prednisone [ Time Frame: At 12 and 24 weeks ]Definition of success: Thirty percent difference between the two groups
- percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator) [ Time Frame: at 12 and 24 weeks ]Definition of success: Thirty percent difference between the two groups
- percentage of participants with immune-related inflammatory arthritis resolution (based on opinion of investigator) [ Time Frame: at 12 and 24 weeks ]Definition of success: Thirty percent difference between the two groups
- percentage of participants with persistent active synovitis/tenosynovitis (yes/no) [ Time Frame: at 12 and 24 weeks ]Differences between treatment groups ≥20% will be considered significant
- percentage of participants treated with methotrexate and/or hydroxychloroquine [ Time Frame: at 12 and 24 weeks ]Differences between treatment groups ≥20% will be considered significant
- MDGA (MD global assessment) of arthritis 0 to 10 [ Time Frame: at weeks 12 and 24 ]Differences between treatment groups ≥20% will be considered significant
- Participant reported pain on a visual analog scale from 0 to 10. [ Time Frame: at weeks 12 and 24 ]Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.
- PGA (patient global assessment) of arthritis 0-10 [ Time Frame: at weeks 12 and 24 ]Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.
- FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue Score) [ Time Frame: at weeks 12 and 24 ]Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.
- EQ-5D (EuroQol 5 Dimension for evaluation of generic quality of life) [ Time Frame: at weeks 12 and 24 ]Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.
- Cancer status vs baseline: overall survival (OS), progression free survival (PFS) [ Time Frame: at 12 and 24 weeks ]Differences between treatment groups ≥20% will be considered significant
- Number of participants who continue, hold or stop ICI therapy [ Time Frame: at 12 and 24 weeks ]Differences between treatment groups ≥20% will be considered significant
- Feasibility: Number of participating sites; Number of participants screened, consented, randomized, and followed-up at each participating site [ Time Frame: at week 24 ]Differences between treatment groups ≥20% will be considered significant
- The rates of AEs, serious AEs (according to CTCAE), and clinical laboratory abnormalities [ Time Frame: at 12 and 24 weeks ]ADA will be considered 'safe' if the frequency of moderate AEs in Group 2 does not exceed 50% (reported rate of moderate AE in RA is 41%)
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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• Patients are deemed eligible for study participation if they meet all the following:
- Adult patients (age 18 or older)
- New (within the last 6 months prior to enrollment) inflammatory arthritis defined by any of the following at the time of screening (either on physical exam or by ultrasound) by a certified rheumatologist:
- 1 or more swollen joints OR
- 1 or more tenosynovitis OR
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1 or more enthesitis
- Arthritis onset with taking ICI therapy OR within 4 weeks of stopping ICI therapy including CTLA-4, PD-1, and PDL-1 inhibitors
- Initiation of ICI therapy must predate the onset of inflammatory arthritis
- Arthritis either does not respond completely to prednisone doses of 10mg (equivalent) OR recurs with prednisone taper below 10mg daily.
- Negative tuberculosis (TB) status within the past 12 months (TB skin test or quantiferon) for the patients in the adalimumab group. If not available, the status should be confirmed within 6 months of enrollment in the study (adalimumab group only)
- Written informed consent provided by patient or power of attorney
Exclusion Criteria:
- Patients are excluded if they meet any of the following:
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Previous diagnosis of inflammatory arthritis or other rheumatic disease (prior to current acute episode)
- Including but not limited to: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, systemic vasculitis, undifferentiated inflammatory arthritis, undifferentiated connective tissue disease
- Tenosynovitis, synovitis or enthesitis attributed to another cause, fracture or acute gout/CPPD flare.
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Presence of a contraindication to adalimumab therapy
- Any of the following in the 7 days prior to initiation of adalimumab: positive tuberculin skin test (>5mm induration within 48 to 72 hours) or positive quantiferon, evidence of untreated active infection including fungal infection, opportunistic infection, hepatitis B/C, or HIV
- Personal history of congestive heart failure
- Personal or family history of demyelinating neurologic disease
- History of previous TNF inhibitor use
- Current use of other disease modifying agents including: Chloroquine, Sulfasalazine, Azathioprine, 6-MP, and Leflunomide
- Presence of a concomitant non-rheumatic irAE which required systemic immunosuppression within the past 3 months e.g. pneumonitis, hepatitis, colitis, scleritis, nephritis
- Require chronic steroid treatment for adrenal insufficiency or another medical reason other than ir-IA
- Pregnancy, breastfeeding or childbearing potential without practicing highly effective contraception.
- Inability to participate in follow-up visits
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06037811
Contact: Tom Appleton, MD, PhD, FRCPC | 519-646-6100 | tom.appelton@sjhc.london.on.ca |
Responsible Party: | Tom Appleton, Principal Investigator, Lawson Health Research Institute |
ClinicalTrials.gov Identifier: | NCT06037811 |
Other Study ID Numbers: |
CanRIO ADA2023 |
First Posted: | September 14, 2023 Key Record Dates |
Last Update Posted: | March 13, 2024 |
Last Verified: | March 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Immune Checkpoint Inhibitor Adalimumab TNF-alpha inhibitor |
Arthritis Joint Diseases Musculoskeletal Diseases Prednisone Adalimumab Anti-Inflammatory Agents Glucocorticoids |
Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Tumor Necrosis Factor Inhibitors Antirheumatic Agents |