Clinical trial NCT06037811: Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis
Official title: Early Adalimumab Induction for Treatment of Steroid Dependent Immune Checkpoint Inhibitor Associated Inflammatory Arthritis: a Pragmatic Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Inflammatory Arthritis
Immune-related Adverse Event
Keywords: Immune Checkpoint Inhibitor
Adalimumab
TNF-alpha inhibitor
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Canadian Research Group in Immuno-Oncology
name: Western University
First posted: 2023-09-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* • 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
* 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:
* 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.
* 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

Primary outcomes:
measure: percentage of participants on prednisone
timeFrame: at 12 weeks
measure: Cumulative prednisone dose
timeFrame: at 12 weeks
Secondary outcomes:
measure: percentage of participants on prednisone
timeFrame: 24 weeks
measure: Cumulative prednisone dose
timeFrame: 24 weeks
measure: percentage of dose reduction of prednisone
timeFrame: At 12 and 24 weeks
measure: percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator)
timeFrame: at 12 and 24 weeks
measure: percentage of participants with immune-related inflammatory arthritis resolution (based on opinion of investigator)
timeFrame: at 12 and 24 weeks
Other outcomes:
measure: percentage of participants with persistent active synovitis/tenosynovitis (yes/no)
timeFrame: at 12 and 24 weeks
measure: percentage of participants treated with methotrexate and/or hydroxychloroquine
timeFrame: at 12 and 24 weeks
measure: MDGA (MD global assessment) of arthritis 0 to 10
timeFrame: at weeks 12 and 24
measure: Participant reported pain on a visual analog scale from 0 to 10.
timeFrame: at weeks 12 and 24
measure: PGA (patient global assessment) of arthritis 0-10
timeFrame: at weeks 12 and 24
measure: FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue Score)
timeFrame: at weeks 12 and 24
measure: EQ-5D (EuroQol 5 Dimension for evaluation of generic quality of life)
timeFrame: at weeks 12 and 24
measure: Cancer status vs baseline: overall survival (OS), progression free survival (PFS)
timeFrame: at 12 and 24 weeks
measure: Number of participants who continue, hold or stop ICI therapy
timeFrame: at 12 and 24 weeks
measure: Feasibility: Number of participating sites; Number of participants screened, consented, randomized, and followed-up at each participating site
timeFrame: at week 24
measure: The rates of AEs, serious AEs (according to CTCAE), and clinical laboratory abnormalities
timeFrame: at 12 and 24 weeks
Locations:
city: London
country: Canada
facility: St. Joseph's Health Care
state: Ontario
Study officials:
References: