Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis

Inflammatory Arthritis Clinical Trial

Official title:

Early Adalimumab Induction for Treatment of Steroid Dependent Immune Checkpoint Inhibitor Associated Inflammatory Arthritis: A Pragmatic Randomized Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06037811
• Other study ID #: CanRIO ADA2023
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 2024
• Est. completion date: November 2025

Study information

• Verified date: March 2024
• Source: Lawson Health Research Institute
• Contact: Tom Appleton, MD, PhD, FRCPC
• Phone: 519-646-6100
• Email: tom.appelton[@]sjhc.london.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Immune-related Adverse Event
• Inflammatory Arthritis

Intervention

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.
• Prednisone
Prednisone as per standard of care.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Tom Appleton	Canadian Research Group in Immuno-Oncology, Western University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	percentage of participants with persistent active synovitis/tenosynovitis (yes/no)	Differences between treatment groups =20% will be considered significant	at 12 and 24 weeks
Other	percentage of participants treated with methotrexate and/or hydroxychloroquine	Differences between treatment groups =20% will be considered significant	at 12 and 24 weeks
Other	MDGA (MD global assessment) of arthritis 0 to 10	Differences between treatment groups =20% will be considered significant	at weeks 12 and 24
Other	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
Other	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
Other	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
Other	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
Other	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
Other	Number of participants who continue, hold or stop ICI therapy	Differences between treatment groups =20% will be considered significant	at 12 and 24 weeks
Other	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
Other	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
Primary	percentage of participants on prednisone	Definition of success: Thirty percent fewer participants on prednisone in Group 2 vs Group 1.	at 12 weeks
Primary	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	percentage of participants on prednisone	Definition of success: Thirty percent difference between the two groups	24 weeks
Secondary	Cumulative prednisone dose	Definition of success: Thirty percent difference between the two groups	24 weeks
Secondary	percentage of dose reduction of prednisone	Definition of success: Thirty percent difference between the two groups	At 12 and 24 weeks
Secondary	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
Secondary	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