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| Name | Class |
|---|---|
| Canadian Research Group in Immuno-Oncology | UNKNOWN |
| Western University | OTHER |
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This study will examine the effectiveness of administering adalimumab as a treatment for patients in the early stages of steroid-dependent immune checkpoint Inhibitor associated inflammatory arthritis (ir-IA). Adalimumab (ADA) is a TNF inhibitor (TNFi) that is well established as a standard of care treatment for numerous types of inflammatory arthritis. It is hoped that adalimumab at the early stages of the ir-IA will reduce the symptoms and therefore reduce the need for steroids. This study is a pragmatic randomized clinical trial. Patients will be randomized 1:1 to each treatment group. To evaluate the steroid sparing effect of early induction six doses of Adalimumab will be administered to patients in the study treatment arm as compared to the usual standard of care of a predefined corticosteroid regimen and taper at 12 weeks administered in the control group.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of care group | Active Comparator | Baseline oral prednisone dose taken daily for one week, then weekly prednisone taper for 12 weeks or until stopped according to the 12-week Glucocorticoid Tapering Schedule |
|
| Adalimumab group | Active Comparator | Adalimumab 40mg SC every 2 weeks x 6 doses + Baseline oral prednisone dose taken daily for one week, then weekly prednisone taper for 12 weeks or until stopped according to the 12-week Glucocorticoid Tapering Schedule. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adalimumab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| percentage of participants on prednisone | Definition of success: Thirty percent fewer participants on prednisone in Group 2 vs Group 1. | at 12 weeks |
| Cumulative prednisone dose | Definition of success: Thirty percent reduction in the cumulative dose of steroids in Group 2 compared to Group 1. | at 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| percentage of participants on prednisone | Definition of success: Thirty percent difference between the two groups | 24 weeks |
| Cumulative prednisone dose | Definition of success: Thirty percent difference between the two groups |
| Measure | Description | Time Frame |
|---|---|---|
| percentage of participants with persistent active synovitis/tenosynovitis (yes/no) | Differences between treatment groups ≥20% will be considered significant | at 12 and 24 weeks |
| percentage of participants treated with methotrexate and/or hydroxychloroquine |
Inclusion Criteria:
• Patients are deemed eligible for study participation if they meet all the following:
1 or more swollen joints OR
1 or more tenosynovitis OR
1 or more enthesitis
Patients requiring prednisone at a dose of at least 10 mg daily (or equivalent) OR
Patients for whom at least 1 glucocorticoid taper failed to control the disease activity
Exclusion Criteria:
Patients are excluded if they meet any of the following:
Previous diagnosis of inflammatory arthritis or other rheumatic disease (prior to current acute episode)
Tenosynovitis, synovitis or enthesitis attributed to another cause, fracture or acute gout/CPPD flare.
Presence of a contraindication to adalimumab therapy
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tom Appleton, MD, PhD, FRCPC | Contact | 519-646-6100 | tom.appelton@sjhc.london.on.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Joseph's Health Care | Recruiting | London | Ontario | N6A 4V2 | Canada |
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| ID | Term |
|---|---|
| D001168 | Arthritis |
| ID | Term |
|---|---|
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D000068879 | Adalimumab |
| D011241 | Prednisone |
| D005938 | Glucocorticoids |
| D000305 | Adrenal Cortex Hormones |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
| Prednisone | Drug | Prednisone as per standard of care. The 12-week glucocorticoid regimen and taper will be standardized between the groups. At Baseline, all participants will be switched to oral prednisone dose at 10, 20, 30, 40, 50, or 60 mg once daily. The initial dose of prednisone is at the discretion of the investigator, based on disease severity and comorbid medical conditions, at a minimum of 10 mg once daily at Baseline. At Baseline, if a participant is on a dose other than 10, 20, 30, 40, 50, or 60 mg QD, the dose will be rounded up or down, as clinically indicated per investigator discretion, to the nearest of these doses. The prednisone taper regimen is tailored to each patient based on the starting dose over a 12-week period. |
|
|
| 24 weeks |
| percentage of dose reduction of prednisone | Definition of success: Thirty percent difference between the two groups | At 12 and 24 weeks |
| percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator) | Definition of success: Thirty percent difference between the two groups | at 12 and 24 weeks |
| percentage of participants with immune-related inflammatory arthritis resolution (based on opinion of investigator) | Definition of success: Thirty percent difference between the two groups | at 12 and 24 weeks |
Differences between treatment groups ≥20% will be considered significant
| at 12 and 24 weeks |
| MDGA (MD global assessment) of arthritis 0 to 10 | Differences between treatment groups ≥20% will be considered significant | at weeks 12 and 24 |
| Participant reported pain on a visual analog scale from 0 to 10. | 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. | at weeks 12 and 24 |
| PGA (patient global assessment) of arthritis 0-10 | 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. | at weeks 12 and 24 |
| FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue Score) | 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. | at weeks 12 and 24 |
| EQ-5D (EuroQol 5 Dimension for evaluation of generic quality of life) | 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. | at weeks 12 and 24 |
| Cancer status vs baseline: overall survival (OS), progression free survival (PFS) | Differences between treatment groups ≥20% will be considered significant | at 12 and 24 weeks |
| Number of participants who continue, hold or stop ICI therapy | Differences between treatment groups ≥20% will be considered significant | at 12 and 24 weeks |
| Feasibility: Number of participating sites; Number of participants screened, consented, randomized, and followed-up at each participating site | Differences between treatment groups ≥20% will be considered significant | at week 24 |
| The rates of AEs, serious AEs (according to CTCAE), and clinical laboratory abnormalities | 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%) | at 12 and 24 weeks |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |