Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease

NCT ID: NCT04925375

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-14

Study Completion Date

2026-07-31

Brief Summary

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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

Detailed Description

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There is no standard of care therapy for patients with granulomatous-lymphocytic interstitial lung disease (GLILD) seen in common variable immunodeficiency (CVID). Abatacept is a recombinant, human fusion protein of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and human IgG1 that blocks T cell activation by binding to CD80 and CD86, thereby blocking CD28 engagement- the "second signal" needed for T cell activation. 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 subjects ≥50 kg and adult subjects (cohort 1), with an additional cohort (#2) of pediatric subjects \<50 kg tested as a single arm, receiving open-label abatacept. Cohort 1 utilizes a 'delayed-start' design to obtain maximum statistical power from this cohort. Cohort 2 will be open label due to the lack of a suitable placebo for pediatric dose abatacept syringes. A total of 21-30 evaluable subjects will be treated in cohort 1 and 8 evaluable subjects in cohort 2.

Following the initial 12 months of treatment, patients will have the option of continuing abatacept for up to 3 years. Patients will have the option of continuing abatacept any time after the initial 12 months of treatment (does not have to be immediately). A separate consent form will be utilized to document a patient's decision to continue. Abatacept will be provided by BMS. Patients who decide to continue abatacept will be monitored for safety, including infections, approximately every 3 months.

Conditions

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Interstitial Lung Disease Common Variable Immunodeficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, blinded/placebo-controlled clinical trial in pediatric and adult subjects ≥50 kg (cohort 1), with an additional cohort (#2) of pediatric subjects \<50 kg tested as a single arm, receiving open-label abatacept
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Abatacept

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 Type EXPERIMENTAL

Abatacept

Intervention Type DRUG

Abatacept is a selective costimulation modulator, inhibiting T lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Orencia solution supplied in a prefilled syringe should be refrigerated at 2C to 8C (36F to 46F). Orencia should not be used beyond the expiration date on the prefilled syringe. The product should be protected from light by storing in the original package until time of use. The prefilled syringe should not be frozen.

Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

The composition of the placebo for Orencia is the same as the active study drug without the abatacept. The placebo will be packaged and labeled as described above for the Orencia prefilled syringes. To maintain the blind, injection volumes will be the same as the active treatment.

Interventions

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Abatacept

Abatacept is a selective costimulation modulator, inhibiting T lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Orencia solution supplied in a prefilled syringe should be refrigerated at 2C to 8C (36F to 46F). Orencia should not be used beyond the expiration date on the prefilled syringe. The product should be protected from light by storing in the original package until time of use. The prefilled syringe should not be frozen.

Intervention Type DRUG

Placebo

The composition of the placebo for Orencia is the same as the active study drug without the abatacept. The placebo will be packaged and labeled as described above for the Orencia prefilled syringes. To maintain the blind, injection volumes will be the same as the active treatment.

Intervention Type OTHER

Other Intervention Names

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Orencia

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of CVID according to the international consensus document (ICON)

1. Age 4 years or above
2. Serum IgG at least 2 standard deviations below the age adjusted normal
3. Decreased serum IgA and/or serum IgM
4. Abnormal specific antibody response to immunization
5. Exclusion of secondary immunodeficiency
2. On replacement immunoglobulin for at least 6 months and willing to maintain throughout study
3. Granulomatous-lymphocytic interstitial lung disease with a lymphocytic component diagnosed by lung biopsy prior to study entry, wedge biopsy preferred.
4. Persistence or worsening of interstitial lung disease measured on serial CT imaging of the lung at least 6 months apart, with the latest assessment within 3 months of study entry.
5. Signed written informed consent
6. Willing to allow storage of biological specimens for future use in medical research.
7. Female subjects of childbearing potential must agree to an effective form of birth control such as hormone based contraceptive, intrauterine device, condoms/barrier, surgically sterile partner, or abstinence.
8. Fertile, non-vasectomized males with a female partner of childbearing potential should use condoms throughout the study and for 3 months after the last dose


* Patients must have completed the abatacept for the treatment of Interstitial Lung Disease in Common Variable Immunodeficiency (ABCVILD) trial
* Patients must have demonstrated positive response to abatacept.
* Patients must provide informed consent to participate in the Extended Treatment Plan.

Exclusion Criteria

1. History of hypersensitivity to abatacept or any of its components
2. Has received any lymphocyte depleting agents including anti-CD20 monoclonal antibodies, alemtuzumab, ATG in the preceding 6 months
3. Has received abatacept, cyclophosphamide, tumor necrosis factor inhibitors, or pulse steroids (defined as \>15mg/kg/day of methylprednisone or corticosteroid equivalent) within the past 3 months
4. Have started or increased any of the following immune modulating drugs within 3 months of enrolling and 3 months from initial CT chest: azathioprine, cyclosporine, tacrolimus, mercaptopurine, methotrexate, mycophenolate mofetil, or sirolimus
5. History of HIV infection (positive PCR)
6. Chronic untreated hepatitis B or C (positive PCR)
7. Active tuberculosis (TB) by positive QuantiFERON gold. If history of latent TB, then must supply evidence of completing treatment.
8. Persistent Epstein-Barr Virus (EBV) load ≥ 1,000 units/mL blood checked twice at least 1 month apart
9. Other uncontrolled infections
10. Live vaccine given within 6 weeks of the start of the trial
11. Malignancy or treated for malignancy within the past year
12. Currently pregnant or breast feeding
13. Life expectancy less than 1 month
14. Subjects unwilling to self-administer or have a parent/caregiver self-administer subcutaneous injections at home
15. Other conditions that the investigators feel contraindicate participation in the study


• Patients who experienced SAEs during the original trial, and such SAEs were determined as related to treatment, or patients who in the opinion of the investigator would not benefit from the extended treatment option.
Minimum Eligible Age

4 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Jordan

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

University of South Florida

Tampa, Florida, United States

Site Status RECRUITING

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Duke University Health System

Durham, North Carolina, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Michael Jordan

Role: CONTACT

Phone: 513-803-9063

Email: [email protected]

Facility Contacts

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Alma Andrade

Role: primary

Jolan Walter

Role: primary

Jocelyn Farmer, MD

Role: primary

Ahmed Sanousi

Role: backup

Dahir Sharif

Role: primary

Katherine Prince

Role: primary

Michael Jordan

Role: primary

Other Identifiers

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R01FD007267

Identifier Type: FDA

Identifier Source: secondary_id

View Link

2020-0876

Identifier Type: -

Identifier Source: org_study_id