Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis

NCT06037811 | Recruiting Phase 2 DMC

• 1 other identifier: CanRIO ADA2023
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Keywords

Immune Checkpoint Inhibitor; Adalimumab; TNF-alpha inhibitor

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (5)

• percentage of participants on prednisone

  24 weeks

• Cumulative prednisone dose

  24 weeks

• percentage of dose reduction of prednisone

  At 12 and 24 weeks

• percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator)

  at 12 and 24 weeks

• percentage of participants with immune-related inflammatory arthritis resolution (based on opinion of investigator)

  at 12 and 24 weeks

Other Outcomes (11)

• percentage of participants with persistent active synovitis/tenosynovitis (yes/no)

  at 12 and 24 weeks

• percentage of participants treated with methotrexate and/or hydroxychloroquine

  at 12 and 24 weeks

• MDGA (MD global assessment) of arthritis 0 to 10

  at weeks 12 and 24

Study Arms (2)

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

Drug: Adalimumab; Drug: Prednisone

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.

Drug: Adalimumab

Interventions

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.

Adalimumab group; Standard of care group

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.

Also known as: Glucocorticoid, Corticosteroid

Standard of care group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• or more swollen joints OR
• or more tenosynovitis OR
• 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
• Glucocorticoid dependence at any time before enrolment, defined by either:
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tom Appleton: lead
• Canadian Research Group in Immuno-Oncology: collaborator
• Western University: collaborator

Study Sites (1)

St. Joseph's Health Care

London, Ontario, N6A 4V2, Canada

RECRUITING

MeSH Terms

Conditions

Arthritis

Interventions

Adalimumab; Prednisone; Glucocorticoids; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Tom Appleton, MD, PhD, FRCPC

CONTACT

519-646-6100; tom.appelton@sjhc.london.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 14, 2023
• Study Start: April 15, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02

Locations

CA (1)