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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04925375
Recruitment Status : Recruiting
First Posted : June 14, 2021
Last Update Posted : November 7, 2023
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE May 11, 2021
First Posted Date  ICMJE June 14, 2021
Last Update Posted Date November 7, 2023
Actual Study Start Date  ICMJE July 14, 2021
Estimated Primary Completion Date July 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2021)
High Resolution CT Scan of the chest (HRCT) [ Time Frame: 6 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2021)
  • Forced vital capacity (FVC) [ Time Frame: 6 months, 12 months ]
    Forced vital capacity (FVC)
  • Forced expiratory volume (FEV) [ Time Frame: 6 months, 12 months ]
    Forced expiratory volume (FEV)
  • Diffusion capacity of carbon monoxide (DLCo) [ Time Frame: 6 months, 12 months ]
    Diffusion capacity of carbon monoxide (DLCo)
  • Incidence [ Time Frame: 6 months, 12 months ]
    Incidence of new onset autoimmune/inflammatory diseases while on abatacept or placebo
  • Resolution [ Time Frame: 6 months, 12 months ]
    Resolution of existing autoimmune/inflammatory diseases while on abatacept or placebo
  • Change in Short Form-36 scores [ Time Frame: 6 months, 12 months ]
    Short Form-36: scoring ranges from 0-100 where a higher score denotes better health
  • Change in PedsQL (Pediatric Quality of Life) Generic Core scores [ Time Frame: 6 months, 12 months ]
    PedsQL Generic Core Scales: items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL. Range of 0-2300 for ages above 4, range of 0-2100 for 4 years old
  • Change in King's Interstitial Lung Disease scores [ Time Frame: 6 months, 12 months ]
    King's Interstitial Lung Disease: scoring ranges from 0-100 where a higher score denotes better health
  • Steroid usage [ Time Frame: 6months, 12 months ]
    Cumulative number of steroids used after 6 months and 12 months
  • Survival [ Time Frame: 6 months, 12 months ]
    Survival at 12 months
  • Pediatric growth - change in height [ Time Frame: 6 months, 12 months ]
    Change in height at 6 and 12 months.
  • Pediatric growth - change in weight [ Time Frame: 6 months, 12 months ]
    Change in weight at 6 and 12 months.
  • Additional Immune Agents [ Time Frame: 6 months, 12 months ]
    Rate of discontinuation of additional immune agents while on study agent
  • Adverse Events/Serious Adverse Events [ Time Frame: 6 months, 12 months ]
    Incidence of adverse events and severe adverse events, compared to placebo
  • Dropout rate [ Time Frame: 6 months, 12 months ]
    Study dropout rate
  • Incidence of concurrent infections [ Time Frame: 6 months, 12 months ]
    Incidence of concurrent infections while on study
  • Treatment of concurrent infections [ Time Frame: 6 months, 12 months ]
    Number of infections per patient which require treatment with antibiotics
  • Complications of concurrent infections [ Time Frame: 6 months, 12 months ]
    Complications of concurrent infections while on study
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease
Official Title  ICMJE 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.

Funding Source - FDA OOPD

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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Interstitial Lung Disease
  • Common Variable Immunodeficiency
Intervention  ICMJE
  • Drug: 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.
    Other Name: Orencia
  • Other: 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.
Study Arms  ICMJE
  • Experimental: 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 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

    Intervention: Drug: Abatacept
  • Placebo Comparator: 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 weekly 26. 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.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 5, 2023)
38
Original Estimated Enrollment  ICMJE
 (submitted: June 7, 2021)
60
Estimated Study Completion Date  ICMJE July 2025
Estimated Primary Completion Date July 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael Jordan 513-803-9063 Michael.Jordan.@cchmc.org
Contact: Erinn Kellner 513-517-2188 Erinn.Kellner@cchmc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04925375
Other Study ID Numbers  ICMJE 2020-0876
R01FD007267 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Children's Hospital Medical Center, Cincinnati
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE Not Provided
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date November 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP