Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis

NCT ID: NCT06037811

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-15
• Study Completion Date: 2025-11-30

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.

Conditions

Inflammatory Arthritis; Immune-related Adverse Event

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard of care group

Prednisone 10 mg daily for 2 weeks, then taper by 2.5 mg every 2 weeks until stopped.

Group Type: ACTIVE_COMPARATOR

Prednisone

Intervention Type: DRUG

Prednisone as per standard of care.

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.

Group Type: ACTIVE_COMPARATOR

Adalimumab

Intervention Type: 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.

Prednisone

Intervention Type: DRUG

Prednisone as per standard of care.

Interventions

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.

Intervention Type: DRUG

Prednisone

Prednisone as per standard of care.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Research Group in Immuno-Oncology

UNKNOWN

Sponsor Role: collaborator

Western University

OTHER

Sponsor Role: collaborator

Tom Appleton

OTHER

Sponsor Role: lead

Responsible Party

Tom Appleton

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

St. Joseph's Health Care

London, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Tom Appleton, MD, PhD, FRCPC

Role: CONTACT

tom.appelton@sjhc.london.on.ca

519-646-6100

Facility Contacts

Maha El-shimy

Role: primary

maha.el-shimy@sjhc.london.on.ca

519-646-6000

Dr. Tom Appleton, MD, FRCPC, PhD

Role: backup

Dr. Janet Pope, MD, FRCPC, MPH

Role: backup

Other Identifiers

CanRIO ADA2023

Identifier Type: -

Identifier Source: org_study_id