NCT03244059

Belimumab Treatment of Emphysema Patients With Anti-GRP78 Autoantibodies

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: University of Alabama at Birmingham · Academic / Other
• Sex: All
• Age: 40 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is intended to be an initial "proof-of-concept" study to show feasibility, validate assays and approaches, and explore dosing and safety of belimumab in pulmonary emphysema patients who have clinically relevant (and quantifiable) autoimmune responses. The primary goal is to determine effects of belimumab on levels of autoantibodies against glucose regulated protein 78 (GRP78) among patients with pulmonary emphysema attributable to cigarette smoking. The investigators hypothesize that belimumab treatment will safely reduce circulating levels of autoantibodies that are associated with emphysema, and comorbidities of this lung disease, including atherosclerosis.

Detailed description

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.

Conditions

• Chronic Obstructive Pulmonary Disease
• Emphysema

Interventions

Type	Name	Description
BIOLOGICAL	Belimumab	Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.
DRUG	Placebo	An identically appearing placebo infusion.

Timeline

• Start date: 2018-08-09
• Primary completion: 2022-04-01
• Completion: 2022-04-01
• First posted: 2017-08-09
• Last updated: 2023-07-18
• Results posted: 2023-07-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study