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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of abatacept (Orencia) for individuals with granulomatous-lymphocytic interstitial lung disease (GLILD) related to common variable immunodeficiency (CVID). With no standard treatment currently available, researchers are testing abatacept's potential benefits. Participants will receive either abatacept or a placebo for six months, after which all will switch to abatacept. The trial seeks individuals diagnosed with CVID and GLILD whose lung condition persists or worsens over time, despite treatment. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that abatacept is likely to be safe for humans?

Research has shown that abatacept is generally safe. In other studies, only 10.5% of patients experienced worsening lung disease over time, suggesting it is well-tolerated. Additionally, abatacept has been linked to a lower risk of death compared to rituximab, providing some confidence in its safety for individuals with lung-related conditions.

While these findings are encouraging, it is important to note that the current clinical trial remains in its early stages. Researchers are still collecting safety information, and they are closely monitoring any potential side effects. Prospective participants may find these points helpful in understanding abatacept's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about abatacept for interstitial lung disease because it offers a unique approach compared to existing treatments. While most current therapies manage symptoms or suppress inflammation broadly, abatacept specifically targets the immune system by modulating T-cell activation. This targeted mechanism may help reduce lung inflammation more precisely, potentially improving lung function with fewer side effects. Additionally, abatacept is administered as a weekly subcutaneous injection, which could be more convenient for patients compared to some existing options that require more frequent dosing or intravenous delivery.

What evidence suggests that abatacept might be an effective treatment for GLILD?

Research has shown that abatacept may help treat lung diseases, particularly in individuals with rheumatoid arthritis (RA) who also have lung issues. Studies have found that abatacept can improve symptoms and reduce lung inflammation in these patients. It stabilizes breathing problems and maintains lung function, whether administered by injection or infusion. Additionally, abatacept has been linked to a lower risk of death compared to other treatments for RA patients with lung disease. In this trial, participants will be randomized to receive either abatacept or a placebo for the first six months. This suggests that abatacept might be a good option for people with similar lung conditions, like those in this trial. ^{3 4 6 7 8}

Who Is on the Research Team?

Michael Jordan

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39407931/

The Therapeutic Efficacy of Abatacept for Rheumatoid ... Abatacept significantly improves RA disease activity and reduces pulmonary inflammation in patients with RA-ILD.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0953620523003096

Abatacept in usual and in non-specific interstitial ... ABA seems equally effective in stabilizing dyspnoea, lung function and radiological impairment in both UIP and NSIP patterns of RA-ILD.

3. rheumatologyadvisor.com rheumatologyadvisor.com/news/route-of-aba-administration-does-not-impact-efficacy-in-ra-ild/

Route of Abatacept Administration Does Not Impact ... The route of ABA administration does not appear to impact its efficacy when treating RA-ILD.

4. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.43332

Association of Abatacept with Lower Mortality Risk Compared ... This study aimed to evaluate the effectiveness and safety of abatacept compared with rituximab in patients with RA-ILD. Methods. An emulated ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33887489/

Efficacy and safety of abatacept in interstitial lung disease ... Current evidence suggests that ABA may be a plausible alternative to treat RA patients with ILD.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9313094/

Safety and Effectiveness of Abatacept in a Prospective Cohort ... As for the safety profile of abatacept, we found the median survival to progression of lung disease to be 72.0 months. Although only 10.5% of patients were ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40693411/

Association of Abatacept with Lower Mortality Risk ... Abatacept was associated with a significantly lower risk of all-cause mortality compared with rituximab (HR 0.689, 95% CI 0.581-0.818) and a reduced risk of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03215927

Study Details | NCT03215927 | Abatacept for the Treatment ... This is a proof of concept study to evaluate the efficacy, safety and tolerability of abatacept in Syn-ILD in a multi-center randomized, placebo-controlled 6- ...