Trial Outcomes & Findings for Belimumab Treatment of Emphysema Patients With Anti-GRP78 Autoantibodies (NCT NCT03244059)

NCT ID: NCT03244059

Last Updated: 2023-07-18

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 17 participants
• Primary outcome timeframe: Plasma concentrations of the anti-GRP78 autoantibodies will be measured pre-treatment and at end of treatment at 210 days (or when subject withdraws)
• Results posted on: 2023-07-18

Participant Flow

Participant milestones

Measure	Belimumab 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	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). Placebo: An identically appearing placebo infusion.
Specific Aim 1 STARTED	11	6
Specific Aim 1 COMPLETED	10	6
Specific Aim 1 NOT COMPLETED	1	0
Specific Aim 2 STARTED	11	6
Specific Aim 2 COMPLETED	10	6
Specific Aim 2 NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Belimumab 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	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). Placebo: An identically appearing placebo infusion.
Specific Aim 1 Physician Decision	1	0
Specific Aim 2 Physician Decision	1	0

Baseline Characteristics

Belimumab Treatment of Emphysema Patients With Anti-GRP78 Autoantibodies

Baseline characteristics by cohort

Measure	Belimumab n=11 Participants 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	Placebo n=6 Participants 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). Placebo: An identically appearing placebo infusion.	Total n=17 Participants Total of all reporting groups
Age, Continuous	69 years STANDARD_DEVIATION 6 • n=93 Participants	69 years STANDARD_DEVIATION 6 • n=4 Participants	69 years STANDARD_DEVIATION 6 • n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Sex: Female, Male Male	9 Participants n=93 Participants	4 Participants n=4 Participants	13 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	5 Participants n=93 Participants	2 Participants n=4 Participants	7 Participants n=27 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants	4 Participants n=4 Participants	10 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	11 participants n=93 Participants	6 participants n=4 Participants	17 participants n=27 Participants

PRIMARY outcome

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

Population: Measured as Optical Density (OD) at 405 nM of ELISA. OD values are proportional to autoantibody concentration.

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

Outcome measures

Measure	Belimumab n=10 Participants 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	Placebo n=6 Participants 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). Placebo: An identically appearing placebo infusion.
Percent Change of Circulating Anti-GRP78 IgG Levels	-17.0 % change Standard Error 5.4	-2.6 % change Standard Error 5.1

SECONDARY outcome

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

Treatment effects on concentrations of pneumococcal polysaccharide-binding antibodies by ELISA

Outcome measures

Measure	Belimumab n=10 Participants 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	Placebo n=6 Participants 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). Placebo: An identically appearing placebo infusion.
Percent Change of Pneumococcal Polysaccharide-binding Antibodies	-14.1 Percent change Standard Error 9.1	-5.0 Percent change Standard Error 6.5

SECONDARY outcome

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

Population: analyzed as % of CD20+ cells among peripheral blood mononuclear cells

Treatment effect on relative percentages of circulating B-cells (CD20+) by flow cytometry

Outcome measures

Measure	Belimumab n=10 Participants 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	Placebo n=6 Participants 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). Placebo: An identically appearing placebo infusion.
Percent Change of Circulating B-cells	-12.2 Percent change Standard Error 4.9	-5.0 Percent change Standard Error 6.5

SECONDARY outcome

Timeframe: Study start to completion (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.

Outcome measures

Measure	Belimumab n=10 Participants 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	Placebo n=6 Participants 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). Placebo: An identically appearing placebo infusion.
Adverse Events	10 Adverse events	4 Adverse events

Adverse Events

Belimumab

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Belimumab n=10 participants at risk 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	Placebo n=6 participants at risk 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). Placebo: An identically appearing placebo infusion.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SAE	10.0% 1/10 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	0.00% 0/6 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.
Cardiac disorders SAE	20.0% 2/10 • Number of events 2 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	0.00% 0/6 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.
Respiratory, thoracic and mediastinal disorders SAE	10.0% 1/10 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	0.00% 0/6 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.

Other adverse events

Measure	Belimumab n=10 participants at risk 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: Belimumab is an anti-BLyS (B-lymphocyte stimulating factor) agent administered by infusion.	Placebo n=6 participants at risk 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). Placebo: An identically appearing placebo infusion.
Nervous system disorders Minor self limited	10.0% 1/10 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	0.00% 0/6 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.
Metabolism and nutrition disorders minor adverse event	10.0% 1/10 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	0.00% 0/6 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.
Gastrointestinal disorders minor adverse event	0.00% 0/10 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	16.7% 1/6 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.
Nervous system disorders minor adverse event	10.0% 1/10 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	0.00% 0/6 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.
Skin and subcutaneous tissue disorders minor adverse event	0.00% 0/10 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	16.7% 1/6 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.
Hepatobiliary disorders minor adverse event	0.00% 0/10 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	16.7% 1/6 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.
Blood and lymphatic system disorders minor adverse event	0.00% 0/10 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.	16.7% 1/6 • Number of events 1 • 210 days or the end of treatment if withdrawn prior to 7 month completion Adverse event tabulated and classified based on severity.

Additional Information

Mark Dransfield MD

University of Alabama at Birmingham

Phone: 205-934-5425

Email: mdransfield@uabmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place