Belimumab Treatment of Emphysema Patients With Anti-GRP78 Autoantibodies (BOTEGA)
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|ClinicalTrials.gov Identifier: NCT03244059|
Recruitment Status : Recruiting
First Posted : August 9, 2017
Last Update Posted : September 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Chronic Obstructive Pulmonary Disease Emphysema||Biological: Belimumab Drug: Placebo||Phase 2|
Specific Aim 1: To conduct a double-blind, Phase IIa trial, in which 18 former smokers with pulmonary emphysema (per chest CT scans), and circulating anti-GRP78 autoantibody levels >mean normal values (by ELISA), will be randomized 2:1 to belimumab vs. placebo. Subjects will receive 8 infusions of either belimumab or placebo over a 6 month interval. Plasma anti-GRP78 will be measured pre-treatment, and at 1, 3, 5, and 7 months. The investigators hypothesize belimumab therapy will more effectively reduce anti-GRP78 IgG autoantibodies, the primary endpoint of this trial, compared to placebo.
Specific Aim 2: To determine effects of the belimumab therapy on secondary endpoints (at the times detailed for Aim 1) that include levels of pneumococcal-binding antibodies (by ELISA), circulating B-cell numbers and phenotypes (by flow cytometry), and the rate and severity of adverse events (AE) at any time during treatment. The investigators hypothesize belimumab will have dose-related effects on B-cell numbers and their differentiation, while minimally reducing host defense antibodies, and will also have an acceptable AE profile.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Patients will be randomly assigned to receive active:placebo in a ratio of 2:1.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double-blinded placebo controlled randomized clinical trial|
|Official Title:||Proof-of-concept Randomized, Double-blind, Phase IIa Study to Show Feasibility, Validate Assays and Approaches, and Explore Dosing and Safety of Belimumab in Pulmonary Emphysema Patients|
|Actual Study Start Date :||August 9, 2018|
|Estimated Primary Completion Date :||July 2020|
|Estimated Study Completion Date :||July 2020|
Subjects randomized to the experimental treatment arm will receive i.v. administrations of belimumab (10 mg/kg), consisting of three "loading" doses, two weeks apart, followed by five (5) more monthly infusions. The final assessment will be performed at month 8.
Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.
Other Name: Benlysta
Placebo Comparator: Placebo
These subjects will be treated with identically appearing placebo i.v. on the same schedule as the experimental arm subjects (i.e., three "loading" doses, two weeks apart, followed by five more monthly infusions. Again, the final assessment will be performed at month 7 (210+10 days after treatment start).
An identically appearing placebo infusion.
- Reduction of circulating anti-GRP78 IgG levels [ Time Frame: Plasma concentrations of the anti-GRP78 autoantibodies will be measured pre-treatment, and at 1, 3, 5, and 7 months after treatment start. ]Anti-GRP78 IgG is a clinically relevant surrogate biomarker of autoimmunity in pulmonary emphysema patients who have clinically relevant (and quantifiable) autoimmune responses
- Pneumococcal polysaccharide-binding antibodies [ Time Frame: Prior to treatment, and at 1, 3, 5, and 7 months after treatment starts ]Treatment effects on concentrations of pneumococcal polysaccharide-binding antibodies by ELISA
- Circulating B-cells [ Time Frame: Prior to treatment, and at 1, 3, 5, and 7 months after treatment starts ]Treatment effects on absolute numbers and phenotypes of circulating B-cells by flow cytometry
- Adverse Events [ Time Frame: Study start to completion (about 7 months) ]Adverse events will be evaluated according to criteria outlined in the National Cancer Institure (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03244059
|Contact: Steven R Duncan, MD||(205) email@example.com|
|United States, Alabama|
|UAB Lung Health Center||Recruiting|
|Birmingham, Alabama, United States, 35205|
|Contact: Elizabeth Westfall 205-934-9282 firstname.lastname@example.org|