Summary

Eligibility
for people ages 4 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
completion around
Principal Investigator
by Michele Pham, MD
Headshot of Michele Pham
Michele Pham

Description

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

Details

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.

Keywords

Interstitial Lung Disease, Common Variable Immunodeficiency, Lung Diseases, Interstitial Lung Diseases, Immunologic Deficiency Syndromes, Abatacept

Eligibility

You can join if…

Open to people ages 4 years and up

  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

You CAN'T join if...

  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

Locations

  • UCSF accepting new patients
    San Francisco California 94143 United States
  • Mayo Clinic accepting new patients
    Rochester Minnesota 55902 United States

Lead Scientist at UCSF

  • Michele Pham, MD
    Dr. Pham is a board-certified Allergist and Immunologist who serves as the Director of Adult Clinical Immunology. Dr. Pham leads UCSF's Complex Clinical Immunology and Primary Immunodeficiency Transition of Care Clinic where she sees patients with infectious disease physicians Dr. Jesse Nussbaum and Dr. David Nguyen and immunologist Dr. Monica Tang.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Children's Hospital Medical Center, Cincinnati
ID
NCT04925375
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 38 study participants
Last Updated