Belimumab Treatment of Emphysema Patients With Anti-GRP78 Autoantibodies

NCT03244059 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB-300000119
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease; Emphysema

Keywords

COPD; belimumab; biologic agent; GRP78

Outcome Measures

Primary Outcomes (1)

• Percent Change of Circulating Anti-GRP78 IgG Levels

  Anti-GRP78 IgG is a clinically relevant surrogate biomarker of autoimmunity in pulmonary emphysema patients who have clinically relevant (and quantifiable) autoimmune responses

  Plasma concentrations of the anti-GRP78 autoantibodies will be measured pre-treatment and at end of treatment at 210 days (or when subject withdraws)

Secondary Outcomes (3)

• Percent Change of Pneumococcal Polysaccharide-binding Antibodies

  Prior to treatment and at end of treatment on day 210 (or the conclusion of treatment if subject withdraws)

• Percent Change of Circulating B-cells

  Prior to treatment, and at treatment end on day 210 or when subject participation is terminated

• Adverse Events

  Study start to completion (7 months)

Study Arms (2)

Belimumab

EXPERIMENTAL

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.

Biological: Belimumab

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

Interventions

Belimumab BIOLOGICAL

Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.

Also known as: Benlysta

Belimumab

Placebo DRUG

An identically appearing placebo infusion.

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A history of past tobacco smoking (\>10 pack years), but quit for \>6 months at the time of enrollment. Smoking cessation will be confirmed by serum cotinine assays.
• Pulmonary emphysema per chest CT scans (F950\>5%). About 60% of COPD patients followed in the LHC registry meet these criteria.6 Chest CTs are routine, standard of practice evaluations for patients with COPD, so no new radiographic studies will be necessary for this project.
• Ability and willingness to give informed consent.
• Plasma anti-GRP78 binding IgG \>mean values in former smokers with no lung disease (standardized OD \>0.390) (hence this is a "personalized medicine" approach). Of the 330 emphysema subjects assayed for anti-GRP78 to date, 111 (67%) met this criterion.
• Age 40-75 y.o. COPD is a disease of older individuals.

You may not qualify if:

• Oral steroids or cellular immunosuppressant use (e.g., cyclophosphamide) within 6 months.
• History or clinical or laboratory evidence of other autoimmune syndromes.
• Inability or unwillingness to complete the treatment and surveillance protocols.
• History of malignant neoplasm within the last 5 years.
• Evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months or those, in the investigator's judgment, pose a significant suicide risk.
• History of a primary immunodeficiency.
• Significant IgG deficiency (IgG level \< 400 mg/dL).
• Have an IgA deficiency (IgA level \< 10 mg/dL).
• Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster or atypical mycobacteria).
• Hospitalization for treatment of infection within 60 days of Day 0.
• Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 0.
• Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior to Day 0.
• History of a positive HIV test or positive screening test for HIV.
• Serologic evidence of current or past Hepatitis B (HB) or Hepatitis C (HC) infection based on positive tests for HBsAg or HBcAb, or HCAb.
• History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

UAB Lung Health Center

Birmingham, Alabama, 35205, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema

Interventions

belimumab

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Mark Dransfield MD
• Organization: University of Alabama at Birmingham

mdransfield@uabmc.edu

205-934-5425

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded placebo controlled randomized clinical trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients will be randomly assigned to receive active:placebo in a ratio of 2:1.

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 9, 2017
• Study Start: August 9, 2018
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: July 18, 2023
• Results First Posted: July 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)