Abatacept for Interstitial Lung Disease

(ABCVILD Trial)

Recruiting at 5 trial locations

Overseen By Michael Jordan

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Replacement immunoglobulin

Must not be taking: Lymphocyte depleting agents, Abatacept

Disqualifiers: HIV, Hepatitis B/C, TB, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 6

Duration: 12 months

38 Participants Needed

Trial Summary

What is the purpose of this trial?

There is no standard of care therapy for patients with granulomatous-lymphocytic interstitial lung disease (GLILD) seen in common variable immunodeficiency (CVID). Abatacept has recently looked promising for the treatment of patients with complex CVID. This study is a multi-site, phase II, randomized, blinded/placebo-controlled clinical trial in pediatric and adult subjects to determine the efficacy of abatacept compared to placebo for treatment of subjects with GLILD in the context of CVID. Funding Source - FDA OOPD

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have started or increased certain immune-modulating drugs within 3 months of enrolling. You also cannot have received certain treatments like abatacept or high-dose steroids in the past 3 months.

What data supports the effectiveness of the drug abatacept for interstitial lung disease?

Research shows that abatacept has been effective in treating interstitial lung disease in patients with rheumatoid arthritis and antisynthetase syndrome, suggesting it may help with similar lung conditions. ^{1 2 3 4 5}

Is abatacept generally safe for humans?

Abatacept has been studied for safety in patients with rheumatoid arthritis and interstitial lung disease, showing it is generally safe for use, whether alone or in combination with other treatments. ^{1 2 3 6 7}

How is the drug abatacept unique for treating interstitial lung disease?

Abatacept is unique for treating interstitial lung disease because it is primarily used for conditions like rheumatoid arthritis and works by modulating the immune system, which may help in conditions where the immune system is involved in lung damage. Unlike other treatments, it specifically targets the underlying immune response, which could be beneficial for patients with interstitial lung disease linked to autoimmune conditions. ^{1 2 3 5 8}

Research Team

Michael Jordan

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for people aged 4 and above with Common Variable Immunodeficiency (CVID) and a specific lung condition diagnosed by biopsy. Participants must have been on immunoglobulin replacement for at least 6 months, agree to birth control if necessary, and consent to future use of their biological samples. Exclusions include recent cancer treatment, uncontrolled infections, certain drug treatments within the past few months, chronic hepatitis B or C, HIV infection, pregnancy or breastfeeding.

Inclusion Criteria

You have an unusual reaction to vaccines.

I have been on immunoglobulin replacement for 6+ months and will continue it.

I have a specific lung condition diagnosed by a lung biopsy.

Exclusion Criteria

You have a history of testing positive for HIV.

You have untreated chronic hepatitis B or C, confirmed by a positive PCR test.

I am willing to self-administer or have someone give me injections at home.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abatacept or placebo weekly for 6 months, followed by abatacept for all participants

12 months

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 3 months

Open-label extension (optional)

Participants may opt into continuation of abatacept treatment for up to 3 years

Up to 3 years

Every 3 months

Treatment Details

Interventions

• Abatacept
• Placebo

Trial Overview The study tests Abatacept's effectiveness against a placebo in treating interstitial lung disease associated with CVID. It's a phase II trial involving multiple sites where participants are randomly assigned to receive either Abatacept or a placebo without knowing which one they're getting.

Participant Groups

Group I: Abatacept Experimental Treatment 1 Intervention

Pediatric subjects weighing \<50 kg will be placed in an single arm with abatacept with dosing based on weight. Pediatric subjects weighing ≥50kg and adult subjects will enter a double blinded, randomization in a 1:2 ratio of subjects to the abatacept treatment group (arm 1) or to the placebo group (arm 2) treated weekly through month 6. After month 6, all subjects will begin receiving abatacept weekly. Pediatric dosing: Abatacept subcutaneous every week: 10-25 kg: 50 mg; 25-50 kg: 87.5 mg; \>50 kg: 125 mg Adult dosing: Abatacept: 125 mg subcutaneous every week

Group II: Placebo Placebo Group 1 Intervention

Pediatric subjects weighing ≥50kg and adult subjects will enter a double blinded, randomization in a 1:2 ratio of subjects to the abatacept treatment group (arm 1) or to the placebo group (arm 2) treated weekly through month 6. The composition of the placebo is the same as the active study drug without the abatacept. To maintain the blind, injection volumes will be the same as the active treatment. After month 6, all subjects will begin receiving abatacept weekly.

Abatacept is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in United States as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in Canada as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Approved in Japan as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

In a study of 57 patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) treated with abatacept for a median of 27.3 months, 71.9% of patients experienced stabilization or improvement in their lung disease, indicating the drug's efficacy.

Abatacept demonstrated a favorable safety profile, with only 10.5% of patients experiencing severe adverse effects, suggesting it is a safe treatment option for RA-ILD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease. Mena-Vázquez, N., Rojas-Gimenez, M., Fuego-Varela, C., et al.[2022]

In a study of 263 rheumatoid arthritis patients with interstitial lung disease, abatacept (ABA) demonstrated significant efficacy by improving disease activity scores (DAS28ESR) from 4.5 to 3.1 after a median follow-up of 12 months, indicating better control of rheumatoid arthritis symptoms.

The treatment was found to be safe, with 91.9% of patients not experiencing worsening dyspnoea, and 87.7% maintaining stable forced vital capacity (FVC) levels, although 23.6% of patients discontinued ABA due to adverse events or lack of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients. Fernández-Díaz, C., Castañeda, S., Melero-González, RB., et al.[2021]

In a study of 190 patients with Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD), abatacept (ABA) was found to effectively stabilize lung function and reduce dyspnoea over 24 months, regardless of whether patients had usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP).

The treatment led to improvements or stabilization in radiological findings for 73.1% of UIP patients and 72.9% of NSIP patients, suggesting that early administration of ABA may help prevent the progression of RA-ILD across different lung disease patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept in usual and in non-specific interstitial pneumonia associated with rheumatoid arthritis. Atienza-Mateo, B., Fernández-Díaz, C., Vicente-Rabaneda, EF., et al.[2023]

In a study of 131 rheumatoid arthritis patients treated with abatacept for over 1 year, only 8.4% experienced deterioration of interstitial lung disease (ILD) during an average follow-up of 47.8 months, indicating that abatacept may have a relatively low risk for worsening ILD.

The use of methotrexate (MTX) was identified as a significant risk factor for ILD deterioration in these patients, suggesting that discontinuing MTX could be a strategy to help prevent worsening lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term deterioration of interstitial lung disease in patients with rheumatoid arthritis treated with abatacept. Mochizuki, T., Ikari, K., Yano, K., et al.[2019]

In a study of eight patients with interstitial lung disease associated with antisynthetase syndrome, abatacept (ABA) therapy led to significant improvements in lung function and symptoms, with notable increases in diffusing lung capacity (DLCO) and quality of life scores.

Abatacept was well-tolerated with no significant adverse events reported, suggesting it may be a safe treatment option for this condition, although further randomized controlled trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of abatacept for interstitial lung disease associated with antisynthetase syndrome: a case series. Xia, N., Hong, SM., Zhang, X., et al.[2023]

In a study of 263 Caucasian patients with rheumatoid arthritis and interstitial lung disease, abatacept (ABA) was found to be equally effective and safe whether used alone or in combination with other medications like methotrexate (MTX) or non-MTX DMARDs.

While all treatment groups showed stabilization or improvement in lung function and disease activity, only the combined ABA groups demonstrated a significant corticosteroid-sparing effect, suggesting that combining ABA with other treatments may help reduce the need for steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept in monotherapy vs combined in interstitial lung disease of rheumatoid arthritis-multicentre study of 263 Caucasian patients. Fernández-Díaz, C., Atienza-Mateo, B., Castañeda, S., et al.[2022]

Abatacept significantly improves health outcomes in patients with rheumatoid arthritis, showing higher likelihoods of achieving American College of Rheumatology (ACR) response rates compared to placebo and other treatments, based on a meta-analysis of 13 randomized control trials involving 5978 patients.

Patients treated with abatacept experienced fewer adverse events compared to those receiving other biologic disease-modifying anti-rheumatic drugs, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. Mohamed Ahamada, M., Wu, X.[2023]

In a study of 63 rheumatoid arthritis patients with interstitial lung disease, abatacept (ABA) treatment led to stabilization in lung function for about two-thirds of patients after an average follow-up of 9.4 months, with some showing improvement in symptoms.

Approximately 50% of patients who underwent chest HRCT scans after 12 months showed stabilization or improvement in lung patterns, suggesting that ABA may be an effective treatment for managing ILD associated with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients. Fernández-Díaz, C., Loricera, J., Castañeda, S., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Abatacept in usual and in non-specific interstitial pneumonia associated with rheumatoid arthritis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Long-term deterioration of interstitial lung disease in patients with rheumatoid arthritis treated with abatacept. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of abatacept for interstitial lung disease associated with antisynthetase syndrome: a case series. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Abatacept in monotherapy vs combined in interstitial lung disease of rheumatoid arthritis-multicentre study of 263 Caucasian patients. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients. [2018]