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

NCT04925375 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0876R01FD007267
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Interstitial Lung Disease; Common Variable Immunodeficiency

Outcome Measures

Primary Outcomes (1)

• High Resolution CT Scan of the chest (HRCT)

  Proportion of subjects achieving a significant response (defined as \>30 percent change in lung tissue disease burden by GLILD) on HRCT after 6 months of abatacept therapy.

  6 months

Secondary Outcomes (18)

• Forced vital capacity (FVC)

  6 months, 12 months

• Forced expiratory volume (FEV)

  6 months, 12 months

• Diffusion capacity of carbon monoxide (DLCo)

  6 months, 12 months

• Incidence

  6 months, 12 months

• Resolution

  6 months, 12 months

Study Arms (2)

Abatacept

EXPERIMENTAL

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

Drug: Abatacept

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Abatacept 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.

Also known as: Orencia

Abatacept

Placebo 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.

Placebo

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CVID according to the international consensus document (ICON)
• Age 4 years or above
• Serum IgG at least 2 standard deviations below the age adjusted normal
• Decreased serum IgA and/or serum IgM
• Abnormal specific antibody response to immunization
• On replacement immunoglobulin for at least 6 months and willing to maintain throughout study
• Granulomatous-lymphocytic interstitial lung disease with a lymphocytic component diagnosed by lung biopsy prior to study entry, wedge biopsy preferred.
• 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.
• Signed written informed consent
• Willing to allow storage of biological specimens for future use in medical research.
• 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.
• 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

You may not qualify if:

• History of hypersensitivity to abatacept or any of its components
• Has received any lymphocyte depleting agents including anti-CD20 monoclonal antibodies, alemtuzumab, ATG in the preceding 6 months
• 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
• 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
• History of HIV infection (positive PCR)
• Chronic untreated hepatitis B or C (positive PCR)
• Active tuberculosis (TB) by positive QuantiFERON gold. If history of latent TB, then must supply evidence of completing treatment.
• Persistent Epstein-Barr Virus (EBV) load ≥ 1,000 units/mL blood checked twice at least 1 month apart
• Other uncontrolled infections
• Live vaccine given within 6 weeks of the start of the trial
• Malignancy or treated for malignancy within the past year
• Currently pregnant or breast feeding
• Life expectancy less than 1 month
• Subjects unwilling to self-administer or have a parent/caregiver self-administer subcutaneous injections at home
• Other conditions that the investigators feel contraindicate participation in the study

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of South Florida

Tampa, Florida, 33620, United States

RECRUITING

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55902, United States

RECRUITING

Duke University Health System

Durham, North Carolina, 27710, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

MeSH Terms

Conditions

Lung Diseases, Interstitial; Common Variable Immunodeficiency

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Michael Jordan

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Jordan

CONTACT

513-803-9063; Michael.Jordan.@cchmc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: June 14, 2021
• Study Start: July 14, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: November 6, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)