RecruitingPhase 2NCT04925375

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

Sponsor

Children's Hospital Medical Center, Cincinnati

Enrollment

38 participants

Start Date

Jul 14, 2021

Study Type

INTERVENTIONAL

Conditions

Interstitial Lung Disease Common Variable Immunodeficiency

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

Eligibility

Min Age: 4 Years

Inclusion Criteria16

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
Exclusion of secondary immunodeficiency
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
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 Criteria16

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
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.

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Interventions

DRUGAbatacept

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.

OTHERPlacebo

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.