Trial Outcomes & Findings for Effects of Interleukin (IL)- 4R-alpha Inhibition on Respiratory Microbiome and Immunologic Correlates in Severe Asthma (NCT NCT05036733)
NCT ID: NCT05036733
Last Updated: 2024-10-23
Results Overview
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.
COMPLETED
PHASE4
15 participants
Baseline (before dupilumab), 1 month
2024-10-23
Participant Flow
Participant milestones
| Measure |
Dupilumab
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Overall Study
STARTED
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15
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Overall Study
COMPLETED
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15
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effects of Interleukin (IL)- 4R-alpha Inhibition on Respiratory Microbiome and Immunologic Correlates in Severe Asthma
Baseline characteristics by cohort
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Age, Continuous
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59 years
STANDARD_DEVIATION 18 • n=5 Participants
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Sex: Female, Male
Female
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7 Participants
n=5 Participants
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Sex: Female, Male
Male
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8 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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15 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race/Ethnicity, Customized
White
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14 Participants
n=5 Participants
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Race/Ethnicity, Customized
Race other than White
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1 Participants
n=5 Participants
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Region of Enrollment
United States
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15 Participants
n=5 Participants
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FEV1:FVC
|
0.75 ratio
STANDARD_DEVIATION 0.12 • n=5 Participants
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Body-mass index
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30.1 (kg/m^2)
STANDARD_DEVIATION 12.7 • n=5 Participants
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Fractional exhaled nitric oxide (FeNO)
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32 parts per billion
STANDARD_DEVIATION 33 • n=5 Participants
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Asthma Control Test (ACT) score
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15 score on a scale
STANDARD_DEVIATION 5 • n=5 Participants
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Sino-nasal outcome test (SNOT-22) score
|
44 score on a scale
STANDARD_DEVIATION 16 • n=5 Participants
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mini-Asthma Quality of Life Questionnaire (mAQLQ) score
|
4.2 score on a scale
STANDARD_DEVIATION 1.2 • n=5 Participants
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alpha-diversity of respiratory (sputum) microbiota: Shannon index
|
3.08 Shannon's index
STANDARD_DEVIATION 0.36 • n=5 Participants
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Relative abundances of respiratory (sputum) microbiota members
Streptococcus salivarius
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17.8 percentages
STANDARD_DEVIATION 14.5 • n=5 Participants
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Relative abundances of respiratory (sputum) microbiota members
Streptococcus sanguinis
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2.2 percentages
STANDARD_DEVIATION 1.2 • n=5 Participants
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Relative abundances of respiratory (sputum) microbiota members
Streptococcus parasanguinis
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10.8 percentages
STANDARD_DEVIATION 8.4 • n=5 Participants
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Relative abundances of respiratory (sputum) microbiota members
Bifidobacterium longum
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0.81 percentages
STANDARD_DEVIATION 1.5 • n=5 Participants
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|
Relative abundances of respiratory (sputum) microbiota members
Tropheryma whipplei
|
2.23 percentages
STANDARD_DEVIATION 2.4 • n=5 Participants
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|
Relative abundances of respiratory (sputum) microbiota members
Bifidobacterium dentium
|
0.55 percentages
STANDARD_DEVIATION 0.8 • n=5 Participants
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Relative abundances of respiratory (sputum) microbiota members
Streptococcus gordonii
|
2.9 percentages
STANDARD_DEVIATION 3.7 • n=5 Participants
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Relative abundances of respiratory (sputum) microbiota members
Parvimonas micra
|
3.5 percentages
STANDARD_DEVIATION 4.5 • n=5 Participants
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Relative abundances of respiratory (sputum) microbiota members
Streptococcus anginosus
|
3.5 percentages
STANDARD_DEVIATION 8.7 • n=5 Participants
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Relative abundances of respiratory (sputum) microbiota members
Rothia mucilaginosa
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7.2 percentages
STANDARD_DEVIATION 5.6 • n=5 Participants
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Respiratory bacterial burden (#bacterial cells, sputum)
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4,622,000,000 bacterial cells
STANDARD_DEVIATION 6,443,000,000 • n=5 Participants
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alpha-diversity of stool microbiota: Shannon index
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3.20 score on a scale
STANDARD_DEVIATION 0.31 • n=5 Participants
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Oral Corticosteroid Use
|
1 Participants
n=5 Participants
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Blood eosinophils
|
200 cells/microliter
STANDARD_DEVIATION 200 • n=5 Participants
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PRIMARY outcome
Timeframe: Baseline (before dupilumab), 1 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=7 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Changes in Alpha-diversity of Respiratory Microbiota
|
0.13 Shannon's index
Standard Deviation 0.29
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PRIMARY outcome
Timeframe: Baseline (before dupilumab), 4 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=7 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Changes in Alpha-diversity of Respiratory Microbiota
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0.14 Shannon's index
Standard Deviation 0.30
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PRIMARY outcome
Timeframe: 1 month, 4 monthsPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=6 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Changes in Alpha-diversity of Respiratory Microbiota
|
-0.09 Shannon's index
Standard Deviation 0.41
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PRIMARY outcome
Timeframe: Baseline (before dupilumab), 1 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=7 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Change in Beta-diversity of Respiratory Microbiota
|
.82 score on a scale
Standard Deviation 0.17
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PRIMARY outcome
Timeframe: Baseline (before dupilumab), 4 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=7 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Change in Beta-diversity of Respiratory Microbiota
|
0.82 score on a scale
Standard Deviation 0.17
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PRIMARY outcome
Timeframe: 1 month, 4 monthsPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=6 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Change in Beta-diversity of Respiratory Microbiota
|
0.81 score on a scale
Standard Deviation 0.19
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PRIMARY outcome
Timeframe: Baseline (before dupilumab), 1 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=7 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Change in Relative Abundances of Microbiota Members
Streptococcus salivarius
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-5.9 percentage of bacterial classification
Standard Deviation 0.09
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Change in Relative Abundances of Microbiota Members
Streptococcus sanguinis
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-2.4 percentage of bacterial classification
Standard Deviation 0.04
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Change in Relative Abundances of Microbiota Members
Streptococcus parasanguinis
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0.03 percentage of bacterial classification
Standard Deviation 0.05
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Change in Relative Abundances of Microbiota Members
Bifidobacterium longum
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0.03 percentage of bacterial classification
Standard Deviation 0.02
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Change in Relative Abundances of Microbiota Members
Tropheryma whipplei
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0.2 percentage of bacterial classification
Standard Deviation 0.04
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Change in Relative Abundances of Microbiota Members
Bifidobacterium dentium
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0.3 percentage of bacterial classification
Standard Deviation 0.01
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Change in Relative Abundances of Microbiota Members
Streptococcus gordonii
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1.0 percentage of bacterial classification
Standard Deviation 0.02
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Change in Relative Abundances of Microbiota Members
Parvimonas micra
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1.6 percentage of bacterial classification
Standard Deviation 0.04
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Change in Relative Abundances of Microbiota Members
Streptococcus anginosus
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1.6 percentage of bacterial classification
Standard Deviation 0.04
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Change in Relative Abundances of Microbiota Members
Rothia mucilaginosa
|
2.0 percentage of bacterial classification
Standard Deviation 0.05
|
PRIMARY outcome
Timeframe: Baseline (before dupilumab), 4 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=7 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
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Change in Relative Abundances of Microbiota Members
Streptococcus salivarius
|
-0.2 percent of bacterial classification
Standard Deviation 0.07
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|
Change in Relative Abundances of Microbiota Members
Streptococcus sanguinis
|
1.1 percent of bacterial classification
Standard Deviation 0.02
|
|
Change in Relative Abundances of Microbiota Members
Streptococcus parasanguinis
|
-2.6 percent of bacterial classification
Standard Deviation 0.1
|
|
Change in Relative Abundances of Microbiota Members
Bifidobacterium longum
|
-1.6 percent of bacterial classification
Standard Deviation 0.04
|
|
Change in Relative Abundances of Microbiota Members
Tropheryma whipplei
|
2.4 percent of bacterial classification
Standard Deviation 0.03
|
|
Change in Relative Abundances of Microbiota Members
Bifidobacterium dentium
|
-3.1 percent of bacterial classification
Standard Deviation 0.07
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|
Change in Relative Abundances of Microbiota Members
Parvimonas micra
|
0.6 percent of bacterial classification
Standard Deviation 0.04
|
|
Change in Relative Abundances of Microbiota Members
Streptococcus gordonii
|
0.05 percent of bacterial classification
Standard Deviation 0.03
|
|
Change in Relative Abundances of Microbiota Members
Streptococcus anginosus
|
1.1 percent of bacterial classification
Standard Deviation 0.04
|
|
Change in Relative Abundances of Microbiota Members
Rothia mucilaginosa
|
-4.0 percent of bacterial classification
Standard Deviation 0.09
|
PRIMARY outcome
Timeframe: 1 month, 4 monthsPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=6 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Change in Relative Abundances of Microbiota Members
Rothia mucilaginosa
|
-2.0 percent of bacterial classification
Standard Deviation 0.05
|
|
Change in Relative Abundances of Microbiota Members
Streptococcus salivarius
|
8.3 percent of bacterial classification
Standard Deviation 0.1
|
|
Change in Relative Abundances of Microbiota Members
Streptococcus sanguinis
|
3.3 percent of bacterial classification
Standard Deviation 0.04
|
|
Change in Relative Abundances of Microbiota Members
Streptococcus parasanguinis
|
-3.5 percent of bacterial classification
Standard Deviation 0.12
|
|
Change in Relative Abundances of Microbiota Members
Bifidobacterium longum
|
-1.6 percent of bacterial classification
Standard Deviation 0.02
|
|
Change in Relative Abundances of Microbiota Members
Tropheryma whipplei
|
0.1 percent of bacterial classification
Standard Deviation 0
|
|
Change in Relative Abundances of Microbiota Members
Bifidobacterium dentium
|
-4.5 percent of bacterial classification
Standard Deviation 0.08
|
|
Change in Relative Abundances of Microbiota Members
Streptococcus gordonii
|
-1.6 percent of bacterial classification
Standard Deviation 0.04
|
|
Change in Relative Abundances of Microbiota Members
Parvimonas micra
|
-1.2 percent of bacterial classification
Standard Deviation 0.02
|
|
Change in Relative Abundances of Microbiota Members
Streptococcus anginosus
|
-0.5 percent of bacterial classification
Standard Deviation 0.01
|
PRIMARY outcome
Timeframe: Baseline (before dupilumab), 1 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=7 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
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|---|---|
|
Change in Respiratory Bacterial Burden
|
-16,117,353,849 cells
Standard Deviation 19,829,305,914
|
PRIMARY outcome
Timeframe: Baseline (before dupilumab), 4 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=7 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Change in Respiratory Bacterial Burden
|
-25,294,991,477 cells
Standard Deviation 44,588,805,244
|
PRIMARY outcome
Timeframe: 1 month, 4 monthsPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
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.
Outcome measures
| Measure |
Dupilumab
n=6 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Change in Respiratory Bacterial Burden
|
-9,927,388,331 cells
Standard Deviation 44,588,805,244
|
PRIMARY outcome
Timeframe: Baseline (before dupilumab), 1 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
α-diversity was calculated using the Shannon diversity index at the species level from stool 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.
Outcome measures
| Measure |
Dupilumab
n=4 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Changes in Alpha-diversity of Stool Microbiota
|
0.07 Shannon's index
Standard Deviation 0.24
|
PRIMARY outcome
Timeframe: Baseline (before dupilumab), 4 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
α-diversity was calculated using the Shannon diversity Index at the species level from stool 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.
Outcome measures
| Measure |
Dupilumab
n=3 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Changes in Alpha-diversity of Stool Microbiota
|
0.04 Shannon's index
Standard Deviation 0.29
|
PRIMARY outcome
Timeframe: 1 month, 4 monthsPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
α-diversity was calculated using the Shannon Diversity Index at the species level from stool samples. Shannon's Diversity Index values were 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.
Outcome measures
| Measure |
Dupilumab
n=2 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Changes in Alpha-diversity of Stool Microbiota
|
0.42 Shannon's index
Standard Deviation 0.67
|
PRIMARY outcome
Timeframe: Baseline (before dupilumab), 1 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
Beta-diversity was calculated using the Bray-Curtis Distance at the species level from stool samples. Samples were obtained baseline and after 1 month on dupilumab and the Bray-Curtis Distance calculated. 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..
Outcome measures
| Measure |
Dupilumab
n=4 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Change in Beta-diversity of Stool Microbiota
|
0.72 score on a scale
Standard Deviation 0.14
|
PRIMARY outcome
Timeframe: Baseline (before dupilumab), 4 monthPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
Beta-diversity was calculated using the Bray-Curtis Distance at the species level from stool 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.
Outcome measures
| Measure |
Dupilumab
n=3 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Change in Beta-diversity of Stool Microbiota
|
0.75 score on a scale
Standard Deviation 0.12
|
PRIMARY outcome
Timeframe: 1 month, 4 monthsPopulation: While 15 participants completed treatment, not all participants were able to provide biosamples. All data collected from available samples is provided here.
Beta-diversity was calculated using the Bray-Curtis Distance at the species level from stool 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.
Outcome measures
| Measure |
Dupilumab
n=2 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Change in Beta-diversity of Stool Microbiota
|
0.71 score on a scale
Standard Deviation 0.14
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 4 monthsRatio of the volume of air exhaled in 1 sec (FEV1) divided by the total volume exhaled (FVC). FEV1/FVC \< 0.70 (or less than lower limit of age-predicted normal) is clinically diagnostic of obstructive lung disease.
Outcome measures
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Forced Expiratory Volume ( FEV1) / Forced Vital Capacity (FVC) Ratio
Visit 1
|
0.75 ratio
Interval 0.53 to 0.91
|
|
Forced Expiratory Volume ( FEV1) / Forced Vital Capacity (FVC) Ratio
Visit 2
|
0.78 ratio
Interval 0.51 to 0.93
|
|
Forced Expiratory Volume ( FEV1) / Forced Vital Capacity (FVC) Ratio
Visit 3
|
0.77 ratio
Interval 0.54 to 0.92
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 4 monthsFEV1 measure reported as a percentage of predicted FEV1.
Outcome measures
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Forced Expiratory Volume (FEV1)
Visit 1
|
85 percent of predicted volume
Interval 54.0 to 120.0
|
|
Forced Expiratory Volume (FEV1)
Visit 2
|
88 percent of predicted volume
Interval 61.0 to 137.0
|
|
Forced Expiratory Volume (FEV1)
Visit 3
|
89 percent of predicted volume
Interval 57.0 to 128.0
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 4 monthsFractional exhaled nitric oxide is a clinical biomarker for type 2 airway inflammation. FeNO \>25 is considered indicative of type 2 airway inflammation.
Outcome measures
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Change in Fractional Exhaled Nitric Oxide (FeNO)
Visit 1
|
32 parts per billion
Interval 5.0 to 127.0
|
|
Change in Fractional Exhaled Nitric Oxide (FeNO)
Visit 2
|
24 parts per billion
Interval 6.0 to 42.0
|
|
Change in Fractional Exhaled Nitric Oxide (FeNO)
Visit 3
|
17 parts per billion
Interval 5.0 to 45.0
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 4 monthsThe Asthma Control Test is a clinically validated questionnaire that assesses level of asthma control based on a 4-week recall of symptoms and daily functioning captured in 5 items. Each item is scored on a 5-point scale, and the total score is the sum of the values for all 5 items (range 5-25). A score of 5 represents worst-controlled asthma and 25 represents best-controlled asthma. An ACT score \>19 indicates well-controlled asthma; the minimal clinically important difference in score is 3.
Outcome measures
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Asthma Control Test (ACT)
Visit 1
|
15 score on a scale
Interval 7.0 to 21.0
|
|
Asthma Control Test (ACT)
Visit 2
|
21 score on a scale
Interval 9.0 to 25.0
|
|
Asthma Control Test (ACT)
Visit 3
|
21 score on a scale
Interval 11.0 to 25.0
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 4 monthsThe mini-Asthma Quality of Life Questionnaire (mAQLQ) consists of 15 questions covering 4 domains: symptoms (5 questions), activity limitations (4 questions), emotional function (3 questions), and environmental stimuli (3 questions). The recall time for the mAQLQ is 2 weeks and each item is scored on a 7-point scale. Total scores per participant are the average of the 15 items and range from 1-7, with higher scores indicative of better quality of life. The minimum clinically important difference is 0.5.
Outcome measures
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Mini Asthma Quality of Life Questionnaire Score (mAQLQ)
Visit 3
|
5.6 score on a scale
Interval 3.5 to 6.9
|
|
Mini Asthma Quality of Life Questionnaire Score (mAQLQ)
Visit 1
|
4.2 score on a scale
Interval 1.9 to 7.0
|
|
Mini Asthma Quality of Life Questionnaire Score (mAQLQ)
Visit 2
|
5.2 score on a scale
Interval 2.7 to 7.0
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 4 monthsThis is a 22 item questionnaire. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as it can be. The score ranges between 0 and 110. A higher score means worse outcome.
Outcome measures
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Sino-nasal Outcome Test (SNOT-22)
Visit 1
|
44 score on a scale
Interval 3.0 to 58.0
|
|
Sino-nasal Outcome Test (SNOT-22)
Visit 2
|
24 score on a scale
Interval 1.0 to 63.0
|
|
Sino-nasal Outcome Test (SNOT-22)
Visit 3
|
21 score on a scale
Interval 5.0 to 56.0
|
SECONDARY outcome
Timeframe: Baseline, 4 monthsCount of participants whose maintenance corticosteroid prescription changed between baseline and 4 months.
Outcome measures
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Change in Prescribed Maintenance Corticosteroid Use (Inhaled or Oral), Between Baseline and 4 Months.
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 4 monthsNumber of asthma exacerbations requiring at least 3 days of oral corticosteroids across the entire study population over the course of the study.
Outcome measures
| Measure |
Dupilumab
n=15 Participants
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Number of Asthma Exacerbations Requiring at Least 3 Days of Oral Corticosteroids
|
1 count of exacerbations
|
Adverse Events
Dupilumab
Serious adverse events
| Measure |
Dupilumab
n=15 participants at risk
Dupilumab: Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia-attributed acute respiratory failure
|
6.7%
1/15 • Number of events 1 • 4 months
Non-serious adverse event information was not collected.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory difficulty requiring hospitalization
|
6.7%
1/15 • Number of events 1 • 4 months
Non-serious adverse event information was not collected.
|
|
Blood and lymphatic system disorders
Acute myeloid leukemia diagnosis
|
6.7%
1/15 • Number of events 1 • 4 months
Non-serious adverse event information was not collected.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place