NCT05036733

Effects of Interleukin (IL)- 4R-alpha Inhibition on Respiratory Microbiome and Immunologic Correlates in Severe Asthma

Completed Phase 4 Results posted Last updated 23 October 2024

What this trial tests

Phase 4 trial testing Dupilumab in Asthma in 15 participants. Completed in 29 June 2023.

Timeline

22 February 2022

Primary endpoint
29 June 2023

29 June 2023

Quick facts

Lead sponsor	University of Michigan
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	basic science
Enrollment	15
Start date	22 February 2022
Primary completion	29 June 2023
Estimated completion	29 June 2023
Sites	1 location across United States

Drugs / interventions tested

• Dupilumab (DUPILUMAB) — full drug profile →

Conditions studied

• Asthma — all drugs for Asthma →

Sponsor

University of Michigan

Who can join

18 and older, any sex, with Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Changes in Alpha-diversity of Respiratory Microbiota Primary · Baseline (before dupilumab), 1 month

α-diversity was calculated using the Shannon Diversity Index at the species level from induced sputum samples obtained at Baseline and after 1 month on dupilumab. The change in diversity was calculated by aggregating all participants' calculated diversity and then finding the difference between time points. A higher Shannon Diversity Index value indicates higher diversity. A value of zero indicates the presence of only one kind of species of bacteria.

Group	Value	95% CI
Dupilumab	0.13	± 0.29

Changes in Alpha-diversity of Respiratory Microbiota Primary · Baseline (before dupilumab), 4 month

α-diversity was calculated using the Shannon Diversity Index at the species level from induced sputum samples obtained at baseline and after 4 months on dupilumab. The change in diversity was calculated by aggregating all participants' calculated diversity and then finding the difference between time points. A higher Shannon Diversity Index value indicates higher diversity. A value of zero indicates the presence of only one kind of species of bacteria.

Group	Value	95% CI
Dupilumab	0.14	± 0.30

Changes in Alpha-diversity of Respiratory Microbiota Primary · 1 month, 4 months

α-diversity was calculated using the Shannon Diversity Index at the species level from induced sputum samples obtained after 1 month and after 4 months on dupilumab. The change in diversity was calculated by aggregating all participants' calculated diversity and then finding the difference between time points. A higher Shannon Diversity Index value indicates higher diversity. A value of zero indicates the presence of only one kind of species of bacteria.

Group	Value	95% CI
Dupilumab	-0.09	± 0.41

Change in Beta-diversity of Respiratory Microbiota Primary · Baseline (before dupilumab), 1 month

Beta-diversity was calculated using the Bray-Curtis Distance at the species level from induced sputum samples obtained at baseline and after 1 month on dupilumab. The change in diversity was calculated by aggregating all participants' distance between time points. Bray-Curtis dissimilarity ranges from 0 to 1. A higher Bray-Curtis Distance, which is unitless, indicates a greater difference in diversity between the time points.

Group	Value	95% CI
Dupilumab	.82	± 0.17

Change in Beta-diversity of Respiratory Microbiota Primary · Baseline (before dupilumab), 4 month

Beta-diversity was calculated using the Bray-Curtis Distance at the species level from induced sputum samples obtained at baseline and after 4 months on dupilumab. The change in diversity was calculated by aggregating all participants' distance between time points. Bray-Curtis dissimilarity ranges from 0 to 1. A higher Bray-Curtis Distance indicates a greater difference in diversity between time points.

Group	Value	95% CI
Dupilumab	0.82	± 0.17

Change in Beta-diversity of Respiratory Microbiota Primary · 1 month, 4 months

Beta-diversity was calculated using the Bray-Curtis Distance at the species level from induced sputum samples obtained after 1 month and after 4 months on dupilumab. The change in diversity was calculated by aggregating all participants' distance between time points. Bray-Curtis dissimilarity ranges from 0 to 1. A higher Bray-Curtis Distance indicates a greater difference in diversity between time points.

Group	Value	95% CI
Dupilumab	0.81	± 0.19

Change in Relative Abundances of Microbiota Members Primary · Baseline (before dupilumab), 1 month

Relative abundance was calculated by finding the proportion of a classified species out of all bacterial classifications in an induced sputum sample. Relative abundance was calculated at baseline and after 1 month on dupilumab. The change in relative abundance of each species across all available samples was calculated by taking the difference between time points.

Streptococcus salivarius

Group	Value	95% CI
Dupilumab	-5.9	± 0.09

Streptococcus sanguinis

Group	Value	95% CI
Dupilumab	-2.4	± 0.04

Streptococcus parasanguinis

Group	Value	95% CI
Dupilumab	0.03	± 0.05

Bifidobacterium longum

Group	Value	95% CI
Dupilumab	0.03	± 0.02

Tropheryma whipplei

Group	Value	95% CI
Dupilumab	0.2	± 0.04

Bifidobacterium dentium

Group	Value	95% CI
Dupilumab	0.3	± 0.01

Streptococcus gordonii

Group	Value	95% CI
Dupilumab	1.0	± 0.02

Parvimonas micra

Group	Value	95% CI
Dupilumab	1.6	± 0.04

Change in Relative Abundances of Microbiota Members Primary · Baseline (before dupilumab), 4 month

Relative abundance was calculated by finding the proportion of a classified species out of all bacterial classifications in an induced sputum sample. Relative abundance was calculated at baseline and after 4 months on dupilumab. The change in relative abundance of each species across all available samples was calculated by taking the difference between time points.

Streptococcus salivarius

Group	Value	95% CI
Dupilumab	-0.2	± 0.07

Streptococcus sanguinis

Group	Value	95% CI
Dupilumab	1.1	± 0.02

Streptococcus parasanguinis

Group	Value	95% CI
Dupilumab	-2.6	± 0.1

Bifidobacterium longum

Group	Value	95% CI
Dupilumab	-1.6	± 0.04

Tropheryma whipplei

Group	Value	95% CI
Dupilumab	2.4	± 0.03

Bifidobacterium dentium

Group	Value	95% CI
Dupilumab	-3.1	± 0.07

Streptococcus gordonii

Group	Value	95% CI
Dupilumab	0.05	± 0.03

Parvimonas micra

Group	Value	95% CI
Dupilumab	0.6	± 0.04

Change in Relative Abundances of Microbiota Members Primary · 1 month, 4 months

Relative abundance was calculated by finding the proportion of a classified species out of all bacterial classifications in an induced sputum sample. Relative abundance was calculated after 1 month and after 4 months on dupilumab. The change in relative abundance of each species across all available samples was calculated by taking the difference between time points.

Streptococcus salivarius

Group	Value	95% CI
Dupilumab	8.3	± 0.1

Streptococcus sanguinis

Group	Value	95% CI
Dupilumab	3.3	± 0.04

Streptococcus parasanguinis

Group	Value	95% CI
Dupilumab	-3.5	± 0.12

Bifidobacterium longum

Group	Value	95% CI
Dupilumab	-1.6	± 0.02

Tropheryma whipplei

Group	Value	95% CI
Dupilumab	0.1	± 0

Bifidobacterium dentium

Group	Value	95% CI
Dupilumab	-4.5	± 0.08

Streptococcus gordonii

Group	Value	95% CI
Dupilumab	-1.6	± 0.04

Parvimonas micra

Group	Value	95% CI
Dupilumab	-1.2	± 0.02

Change in Respiratory Bacterial Burden Primary · Baseline (before dupilumab), 1 month

Bacterial burden was estimated by scaling species relative abundances to a known cell count of Imtechella halotolerans (Zymo) that was spiked into an induced sputum sample before extraction for sequencing. Bacterial burden was calculated at baseline and after 1 month on dupilumab. The change in bacterial burden was calculated by aggregating all burden values per participant and taking the difference between time points.

Group	Value	95% CI
Dupilumab	-16,117,353,849	± 19,829,305,914

Change in Respiratory Bacterial Burden Primary · Baseline (before dupilumab), 4 month

Bacterial burden was estimated by scaling all species relative abundances to a known cell count of Imtechella halotolerans that was spiked into sputum samples before extraction for sequencing. Bacterial burden was calculated at baseline and after 4 months on dupilumab. The change in bacterial burden was calculated by aggregating all burden values per participant and taking the difference between time points.

Group	Value	95% CI
Dupilumab	-25,294,991,477	± 44,588,805,244

Change in Respiratory Bacterial Burden Primary · 1 month, 4 months

Bacterial Burden was estimated by scaling the species relative abundance to a known cell count of I. Halotolerans that was spiked into an induced sputum sample before extraction for sequencing. Bacterial burden was calculated at after 1 month and after 4 months on dupilumab. The change in bacterial burden was calculated by aggregating all burden values per participant and taking the difference between time points.

Group	Value	95% CI
Dupilumab	-9,927,388,331	± 44,588,805,244

Adverse events — posted to ClinicalTrials.gov

Time frame: 4 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dupilumab

Serious: 2/15 (13%)

Deaths: 0/15

Serious adverse events (3 terms)

Reaction	System	Dupilumab
Pneumonia-attributed acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—
Respiratory difficulty requiring hospitalization	Respiratory, thoracic and mediastinal disorders	—
Acute myeloid leukemia diagnosis	Blood and lymphatic system disorders	—

Most-reported serious reactions: Pneumonia-attributed acute respiratory failure, Respiratory difficulty requiring hospitalization, Acute myeloid leukemia diagnosis.

Data from ClinicalTrials.gov NCT05036733 adverse events section.

Sponsor's own description

The overall goal of this study is to understand biological responses related to dupilumab treatment among severe asthma patients.

Not all asthma is the same, and characteristics of asthma vary from person to person. The study will investigate whether the study drug can help to improve the health of participants lungs, boost immune response, as well as improve quality of life.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Dupilumab and tezepelumab in severe refractory asthma: new opportunities.
   Ragnoli B, Morjaria J, Pignatti P, Montuschi P, et al · · 2022 · cited 7× · PMID 35655942 · DOI 10.1177/20406223221097327