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
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. Following the initial 12 months of treatment, patients will have the option of continuing abatacept for up to 3 years. Patients will have the option of continuing abatacept any time after the initial 12 months of treatment (does not have to be immediately). A separate consent form will be utilized to document a patient's decision to continue. Abatacept will be provided by BMS. Patients who decide to continue abatacept will be monitored for safety, including infections, approximately every 3 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
38
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.
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.
University of California, San Francisco
San Francisco, California, United States
RECRUITINGUniversity of South Florida
Tampa, Florida, United States
RECRUITINGLahey Hospital and Medical Center
Burlington, Massachusetts, United States
RECRUITINGMayo Clinic
Rochester, Minnesota, United States
RECRUITINGDuke University Health System
Durham, North Carolina, United States
RECRUITINGCincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
RECRUITINGHigh 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.
Time frame: 6 months
Forced vital capacity (FVC)
Forced vital capacity (FVC)
Time frame: 6 months, 12 months
Forced expiratory volume (FEV)
Forced expiratory volume (FEV)
Time frame: 6 months, 12 months
Diffusion capacity of carbon monoxide (DLCo)
Diffusion capacity of carbon monoxide (DLCo)
Time frame: 6 months, 12 months
Incidence
Incidence of new onset autoimmune/inflammatory diseases while on abatacept or placebo
Time frame: 6 months, 12 months
Resolution
Resolution of existing autoimmune/inflammatory diseases while on abatacept or placebo
Time frame: 6 months, 12 months
Change in Short Form-36 scores
Short Form-36: scoring ranges from 0-100 where a higher score denotes better health
Time frame: 6 months, 12 months
Change in PedsQL (Pediatric Quality of Life) Generic Core scores
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
Time frame: 6 months, 12 months
Change in King's Interstitial Lung Disease scores
King's Interstitial Lung Disease: scoring ranges from 0-100 where a higher score denotes better health
Time frame: 6 months, 12 months
Steroid usage
Cumulative number of steroids used after 6 months and 12 months
Time frame: 6months, 12 months
Survival
Survival at 12 months
Time frame: 6 months, 12 months
Pediatric growth - change in height
Change in height at 6 and 12 months.
Time frame: 6 months, 12 months
Pediatric growth - change in weight
Change in weight at 6 and 12 months.
Time frame: 6 months, 12 months
Additional Immune Agents
Rate of discontinuation of additional immune agents while on study agent
Time frame: 6 months, 12 months
Adverse Events/Serious Adverse Events
Incidence of adverse events and severe adverse events, compared to placebo
Time frame: 6 months, 12 months
Dropout rate
Study dropout rate
Time frame: 6 months, 12 months
Incidence of concurrent infections
Incidence of concurrent infections while on study
Time frame: 6 months, 12 months
Treatment of concurrent infections
Number of infections per patient which require treatment with antibiotics
Time frame: 6 months, 12 months
Complications of concurrent infections
Complications of concurrent infections while on study
Time frame: 6 months, 12 months
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