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

Brief Title

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

Official Title

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

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.
    

Detailed Description

      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 adult and pediatric subjects ≥50 kg (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 45 evaluable subjects will be treated in cohort 1 and 15
      evaluable subjects in cohort 2.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

High Resolution CT Scan of the chest (HRCT)

Secondary Outcome

 Forced vital capacity (FVC)

Condition

Interstitial Lung Disease

Intervention

Abatacept

Study Arms / Comparison Groups

 Abatacept
Description:  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 weekly 26.
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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

60

Start Date

July 14, 2021

Completion Date

July 2025

Primary Completion Date

July 2025

Eligibility Criteria

        Inclusion Criteria:

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

             a Age 4 years or above

             b. Serum IgG at least 2 standard deviations below the age adjusted normal

             c. Decreased serum IgA and/or serum IgM

             d. Abnormal specific antibody response to immunization

             e. 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 2 months of study
             entry.

          5. Signed written informed consent

          6. Willing to allow storage of biological specimens for future use in medical research.

          7. Females of childbearing potential must use a highly effective form of birth control
             such as hormone-based contraceptive, intrauterine device, or double barrier method.

        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. History of HIV infection (positive PCR)

          5. Chronic untreated hepatitis B or C (positive PCR)

          6. Active tuberculosis (TB) by positive QuantiFERON gold. If history of latent TB, then
             must supply evidence of completing treatment.

          7. Persistent Epstein-Barr Virus (EBV) load ≥ 1,000 units/mL blood checked twice at least
             1 month apart

          8. Other uncontrolled infections

          9. Live vaccine given within 6 weeks of the start of the trial

         10. Malignancy or treated for malignancy within the past year

         11. Currently pregnant or breast feeding

         12. Life expectancy less than 1 month

         13. Subjects unwilling to self-administer or have a parent/caregiver self-administer
             subcutaneous injections at home

         14. Other conditions that the investigators feel contraindicate participation in the study
      

Gender

All

Ages

4 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 513-803-9063, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04925375

Organization ID

2020-0876


Responsible Party

Sponsor

Study Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

 Bristol-Myers Squibb

Study Sponsor

, , 


Verification Date

July 2021