AS201: Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma

Sponsor

Knopp Biosciences (Industry)

Overall Status

Completed

CT.gov ID

NCT04046939

Collaborator

(none)

534

Enrollment

Locations

Arms

18.6

Actual Duration (Months)

14.8

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, multi-center study to evaluate the clinical effects of oral administration of dexpramipexole for 12 weeks on peripheral blood eosinophil count in subjects with eosinophilic asthma.

Condition or Disease	Intervention/Treatment	Phase
Eosinophilic Asthma Asthma	Drug: Dexpramipexole Drug: Placebo	Phase 2

Detailed Description

One hundred subjects will receive study drug or matching placebo over 12 weeks of consecutive dosing. Following a short Run-in Period, eligible subjects will enter the Primary Assessment Period and receive twice-daily dosing of study drug or placebo for 12 weeks. Following 12 weeks of treatment, subjects will enter a 12-week Eosinophil Recovery Period. The primary endpoint for the study is the change in blood absolute eosinophil count from Baseline to Week 12.

Study Design

Study Type:

Interventional

Actual Enrollment :

534 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Four-arm parallel assignmentFour-arm parallel assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Biomarker Study of the Effects of Dexpramipexole on Eosinophils in Subjects With Eosinophilic Asthma

Actual Study Start Date :

Aug 15, 2019

Actual Primary Completion Date :

Dec 3, 2020

Actual Study Completion Date :

Mar 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo BID Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks.	Drug: Placebo placebo twice daily oral dosing for up to 12 weeks Other Names: PBO
Active Comparator: 37.5 mg BID dexpramipexole Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks.	Drug: Dexpramipexole dexpramipexole twice daily oral dosing for up to 12 weeks Other Names: KNS-760704 BIIB050
Active Comparator: 75 mg BID dexpramipexole Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks.	Drug: Dexpramipexole dexpramipexole twice daily oral dosing for up to 12 weeks Other Names: KNS-760704 BIIB050
Active Comparator: 150 mg BID dexpramipexole Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks.	Drug: Dexpramipexole dexpramipexole twice daily oral dosing for up to 12 weeks Other Names: KNS-760704 BIIB050

Outcome Measures

Primary Outcome Measures

Change in Blood Absolute Eosinophil Count From Baseline to Week 12 [Baseline, 12 Weeks]
The primary endpoint of this study was the change in AEC from Baseline to Week 12 on a ratio scale. The analysis used a mixed effects model repeated-measures (MMRM) with terms for log10 transformed baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and log10 transformed baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the log10 transformed post-baseline value minus the log10 transformed baseline value. The estimates of Geometric LS Means and their ratios were obtained by back transforming the corresponding estimates of LS means and their differences to the original scale.

Secondary Outcome Measures

Change in Pre-bronchodilator FEV1 (Liters) From Baseline to Week 12 [Baseline, 12 Weeks]
FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Change in Asthma Control Questionnaire (ACQ-6) Score From Baseline to Week 12 [Baseline, 12 Weeks]
ACQ-6 is simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment. The 6-point self-administered scale has items measuring asthma symptoms and rescue inhaler use. The ACQ score is the mean of the questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). The original protocol planned to analyze the ACQ-7 score. As a result of FEV1 testing restrictions imposed on the study during the COVID-19 pandemic, the analysis was prospectively modified to the ACQ-6 score prior to database lock. The ACQ-6 is a validated questionnaire and is identical to the ACQ-7, with the exception of FEV1 data that is also utilized in the ACQ-7 questionnaire total score calculation.
Change in Post-bronchodilator FEV1 From Baseline to Week 12 [Baseline, 12 Weeks]
Post-bronchodilator FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation, after treatment with inhaled albuterol.
Change in Quality of Life, as Measured by the Asthma Quality of Life Questionnaire (AQLQ) From Baseline to Week 12 [Baseline, 12 Weeks]
The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma. The 32 questions in the AQLQ are divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions and ranges from 1 to 7. A score 7.0 indicates that the patient has no impairments due to asthma and score 1.0 indicates severe impairment.
Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group Post Randomization Through Week 12 [Immediately post-baseline up to Week 12]
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group Post Randomization Through Week 12 [Immediately post-baseline up to Week 12]
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Number of Participants With Potentially Clinically Significant Urinalysis Results by Treatment Group Post Randomization Through Week 12 [Immediately post-baseline up to Week 12]
Number of Participants with Potentially Clinically Significant Urinalysis Results (glycosuria, ketonuria, or proteinuria) by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline urinalysis value in each treatment group. Patients are only counted once per criterion per laboratory test. The number of participants with potential clinical important urinalysis findings at any post-baseline visit were reported.
Number of Participants With Potentially Clinically Significant Vital Signs Results by Treatment Group Post Randomization Through Week 12 [Immediately post-baseline up to Week 12]
Number of Participants with Potentially Clinically Significant Vital Signs Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Number of Participants With Potentially Clinically Significant ECG Results by Treatment Group Post Randomization Through Week 12 [Immediately post-baseline up to Week 12]
Number of Participants with Potentially Clinically Significant ECG Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.

Other Outcome Measures

Change in Nasal Eosinophil Peroxidase (Presented as Ratio to Protein) From Baseline to Week 12 [Baseline, Week 12]
The EPX:protein ratio was used to normalize the EPX for the quantity of sample, yielding the values in ng EPX per mg protein. The ratio of nasal Eosinophil Peroxidase to Protein is a biomarker for airway eosinophils. A lower ratio to Baseline represents a lowering in airway eosinophilia, which is a marker of successful drug therapy.
Change in Blood Absolute Blood Basophil Count From Baseline to Week 12 [Baseline, Week 12]
The analysis used a mixed effects model repeated-measures MMRM with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value. Basophils were enumerated as part of the WBC automated differential performed by the Central Laboratory.
Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 12 [Baseline, Week 12]
FeNO is non-invasive biomarker of airway inflammation in asthma participants.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female ≥18 and <75 years of age at the time of consent
Physician diagnosis of asthma for ≥12 months (relative to Baseline) based on Global Initiative for Asthma (GINA) 2018 Guidelines
Asthma requiring treatment with, at a minimum, low dose inhaled corticosteroids in combination with a long-acting β2 agonist, on a stable dose for at least 1 month before Screening
Bronchodilator reversibility, as evidenced by ≥12% and ≥200 mL improvement in FEV1 15 to 25 minutes following inhalation of albuterol at Screening
Pre-bronchodilator FEV1 ≥40% and <80% of predicted at Screening and Baseline
AEC ≥0.30 x10^9/L at the Screening visit
ACQ-7 ≥1.5 at Screening
Negative pregnancy test at Baseline
Adherence ≥85% with twice-daily placebo taken during the Run-in Period

Exclusion Criteria:

Treatment for an asthma exacerbation within 8 weeks prior to Baseline visit
Treatment with systemic corticosteroids in the 8 weeks prior to Screening
Treatment with monoclonal antibody therapy, within 5-half-lives prior to Baseline
Treatment with selected drugs known to have a substantial risk of neutropenia
Absolute neutrophil count <2.0x10^{9/L at Screening, or any documented history of
absolute neutrophil count <2.0x10}9/L.
Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2 at Screening
Clinically significant abnormal laboratory or ECG values
Other medically significant illness
Use of any smoke or inhaled nicotine delivery device within 1 year prior to Screening
Pregnant women or women breastfeeding
Currently taking pramipexole or other dopamine agonists

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States	90048
2	Research Site	Mission Viejo	California	United States	92691
3	Research Site	Westminster	California	United States	92683
4	Research Site	Denver	Colorado	United States	80230
5	Research Site	Daytona Beach	Florida	United States	32117
6	Research Site	Miami	Florida	United States	33186
7	Research Site	Orlando	Florida	United States	32803
8	Research Site	Tampa	Florida	United States	33612
9	Research Site	Tampa	Florida	United States	33634
10	Research Site	Lawrenceville	Georgia	United States	30046
11	Research Site	Winder	Georgia	United States	30680
12	Research Site	Boise	Idaho	United States	83706
13	Research Site	Farmington Hills	Michigan	United States	48336
14	Research site	Plymouth	Minnesota	United States	55441
15	Research Site	Saint Louis	Missouri	United States	63110
16	Research Site	Saint Louis	Missouri	United States	63141
17	Research Site	Las Vegas	Nevada	United States	89119
18	Research Site	New Brunswick	New Jersey	United States	08901
19	Research Site	Corning	New York	United States	14830
20	Research Site	New Hyde Park	New York	United States	11042
21	Research Site	Raleigh	North Carolina	United States	27607
22	Research Site	Winston-Salem	North Carolina	United States	27103
23	Research Site	Cincinnati	Ohio	United States	45231
24	Research Site	Cincinnati	Ohio	United States	45242
25	Research Site	Columbus	Ohio	United States	43235
26	Research Site	Dublin	Ohio	United States	43016
27	Research Site	Edmond	Oklahoma	United States	73034
28	Research Site	Medford	Oregon	United States	97504
29	Research Site	Portland	Oregon	United States	97202
30	Research Site	Pittsburgh	Pennsylvania	United States	15205
31	Research Site	Anderson	South Carolina	United States	29621
32	Research Site	North Charleston	South Carolina	United States	29406
33	Research Site	Allen	Texas	United States	75013
34	Research Site	Boerne	Texas	United States	78006
35	Research Site	Dallas	Texas	United States	75240
36	Research Site	El Paso	Texas	United States	79902

Sponsors and Collaborators

Knopp Biosciences

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Knopp Biosciences

ClinicalTrials.gov Identifier:

NCT04046939

Other Study ID Numbers:

KNS-760704-AS201

First Posted:

Aug 6, 2019

Last Update Posted:

Mar 28, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Knopp Biosciences

Eosinophilic Asthma

Asthma

dexpramipexole

Additional relevant MeSH terms:

Asthma

Pulmonary Eosinophilia

Pramipexole

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Of the 534 participants enrolled, 144 subjects received placebo treatment during the Run-in Period. Of those, 103 completed the Run-in Period, were eligible for randomization, and entered the Primary Assessment Period.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Period Title: Screening Period
STARTED	534	0	0	0
Received Placebo During Run-In Period	144	0	0	0
COMPLETED	103	0	0	0
NOT COMPLETED	431	0	0	0
Period Title: Screening Period
STARTED	27	22	26	28
COMPLETED	25	22	24	28
NOT COMPLETED	2	0	2	0
Period Title: Screening Period
STARTED	25	22	24	28
COMPLETED	24	22	24	27
NOT COMPLETED	1	0	0	1

Baseline Characteristics

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole	Total
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Total of all reporting groups
Overall Participants	27	22	26	28	103
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.8 (12.89)	46.6 (13.41)	44.5 (15.46)	44.6 (12.53)	45.3 (13.42)
Age, Customized (Count of Participants)
<50 years	15 55.6%	14 63.6%	15 57.7%	18 64.3%	62 60.2%
50 to 65 years	10 37%	6 27.3%	8 30.8%	9 32.1%	33 32%
>65 years	2 7.4%	2 9.1%	3 11.5%	1 3.6%	8 7.8%
Sex: Female, Male (Count of Participants)
Female	17 63%	11 50%	14 53.8%	12 42.9%	54 52.4%
Male	10 37%	11 50%	12 46.2%	16 57.1%	49 47.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 7.4%	3 13.6%	3 11.5%	3 10.7%	11 10.7%
Not Hispanic or Latino	25 92.6%	19 86.4%	23 88.5%	25 89.3%	92 89.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 3.8%	0 0%	1 1%
Asian	1 3.7%	1 4.5%	2 7.7%	0 0%	4 3.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 14.8%	4 18.2%	6 23.1%	6 21.4%	20 19.4%
White	21 77.8%	17 77.3%	16 61.5%	22 78.6%	76 73.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.7%	0 0%	1 3.8%	0 0%	2 1.9%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	34.31 (12.749)	31.73 (7.379)	33.44 (10.690)	32.13 (7.040)	32.95 (9.738)

Outcome Measures

1. Primary Outcome

Title	Change in Blood Absolute Eosinophil Count From Baseline to Week 12
Description	The primary endpoint of this study was the change in AEC from Baseline to Week 12 on a ratio scale. The analysis used a mixed effects model repeated-measures (MMRM) with terms for log10 transformed baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and log10 transformed baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the log10 transformed post-baseline value minus the log10 transformed baseline value. The estimates of Geometric LS Means and their ratios were obtained by back transforming the corresponding estimates of LS means and their differences to the original scale.
Time Frame	Baseline, 12 Weeks

Outcome Measure Data

Analysis Population Description
The efficacy population will be a modified intent-to-treat sample and consist of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who have at least one post-randomization AEC evaluation.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	25	22	24	28
Geometric Least Squares Mean (Standard Error) [ratio to baseline]	0.8980 (1.26)	0.4031 (1.28)	0.3056 (1.27)	0.2051 (1.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 150 mg BID Dexpramipexole
	Comments	The 150 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<.0001
	Comments	A closed hierarchical procedure testing dexpramipexole against placebo at Week 12 was used. (1) 150 mg BID for AEC (2) 75 mg BID for AEC (3) pooled 75 mg and 150 mg BID group for pre-bronchodilator FEV1; and (4) 37.5 mg BID for AEC.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Ratio to PBO of the ratios to baseline
	Estimated Value	0.2283
	Confidence Interval	(2-Sided) 95% 0.121 to 0.431
	Parameter Dispersion	Type: Value:
	Estimation Comments	0.2283 represents the ratio of the 150 mg BID week 12 ratio to baseline (0.2051), compared to the PBO week 12 ratio to baseline (0.8980). This ratio of 0.2283 is equivalent to a -77.17% change compared to placebo at week 12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 75 mg BID Dexpramipexole
	Comments	The 75 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0014
	Comments	A closed hierarchical procedure testing dexpramipexole against placebo at Week 12 was used. (1) 150 mg BID for AEC (2) 75 mg BID for AEC (3) pooled 75 mg and 150 mg BID group for pre-bronchodilator FEV1; and (4) 37.5 mg BID for AEC.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Ratio to PBO of the ratios to baseline
	Estimated Value	0.3403
	Confidence Interval	(2-Sided) 95% 0.177 to 0.653
	Parameter Dispersion	Type: Value:
	Estimation Comments	0.3403 represents the ratio of the 75 mg BID week 12 ratio to baseline (0.3056), compared to the PBO week 12 ratio to baseline (0.8980). This ratio of 0.3403 is equivalent to a -65.97% change compared to placebo at week 12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 37.5 mg BID Dexpramipexole
	Comments	The 37.5 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0190
	Comments	A closed hierarchical statistical testing was used. The previous endpoint in the hierarchy was not statistically significant. Therefore, this endpoint was not formally tested and is not considered statistically significant, despite a p-value <0.05.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Ratio to PBO of the ratios to baseline
	Estimated Value	0.4489
	Confidence Interval	(2-Sided) 95% 0.231 to 0.874
	Parameter Dispersion	Type: Value:
	Estimation Comments	0.4489 represents the ratio of the 37.5 mg BID week 12 ratio to baseline (0.4031) compared to the PBO week 12 ratio to baseline (0.8980). This ratio of 0.4489 is equivalent to a -55.11% change compared to placebo at week 12.

2. Secondary Outcome

Title	Change in Pre-bronchodilator FEV1 (Liters) From Baseline to Week 12
Description	FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Time Frame	Baseline, 12 Weeks

Outcome Measure Data

Analysis Population Description
The efficacy population will be a modified intent-to-treat sample and consist of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who have at least one post-randomization FEV1 evaluation. Spirometry restrictions were put in place during the COVID-19 pandemic. Subjects who did not complete the Week 8 and Week 12 post dose assessments due to these restrictions were excluded from this analysis.

Analysis Population Description

The efficacy population will be a modified intent-to-treat sample and consist of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who have at least one post-randomization FEV1 evaluation. Spirometry restrictions were put in place during the COVID-19 pandemic. Subjects who did not complete the Week 8 and Week 12 post dose assessments due to these restrictions were excluded from this analysis.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole	Combined 150 mg BID and 75 mg BID Arms
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects in this combined treatment group received 1 tablet of either 150 mg dexpramipexole twice daily for 12 weeks or 75 mg dexpramipexole trice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	17	18	21	24	45
Least Squares Mean (Standard Error) [liters]	0.0700 (0.08329)	0.208 (0.08387)	0.0557 (0.07848)	0.247 (0.07769)	0.151 (0.05746)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, Combined 150 mg BID and 75 mg BID Arms
	Comments	The combined 75 mg and 150 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4154
	Comments	A closed hierarchical procedure testing dexpramipexole against placebo at Week 12 was used. (1) 150 mg BID for AEC (2) 75 mg BID for AEC (3) pooled 75 mg and 150 mg BID group for pre-bronchodilator FEV1; and (4) 37.5 mg BID for AEC.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0814
	Confidence Interval	(2-Sided) 95% -0.116 to 0.279
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the pooled 75 mg and 150 mg BID group from placebo in change in pre-bronchodilator FEV1 in liters from Baseline to Week 12 (end of primary treatment period). A positive value indicates improvement in lung function.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 150 mg BID Dexpramipexole
	Comments	The 150 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1174
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.177
	Confidence Interval	(2-Sided) 95% -0.0456 to 0.400
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 150 mg BID group from the placebo group in the change in pre-bronchodilator FEV1 in liters from Baseline to Week 12 (end of primary treatment period). A positive value indicates improvement in lung function.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 75 mg BID Dexpramipexole
	Comments	The 75 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8998
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0143
	Confidence Interval	(2-Sided) 95% -0.240 to 0.211
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 75 mg BID group from the placebo group in the change in pre-bronchodilator FEV1 in liters from Baseline to Week 12 (end of primary treatment period). A positive value indicates improvement in lung function.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 37.5 mg BID Dexpramipexole
	Comments	The 37.5 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2425
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.138
	Confidence Interval	(2-Sided) 95% -0.0950 to 0.370
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 37.5 mg BID group from the placebo group in the change in pre-bronchodilator FEV1 in liters from Baseline to Week 12 (end of primary treatment period). A positive value indicates improvement in lung function.

3. Secondary Outcome

Title	Change in Asthma Control Questionnaire (ACQ-6) Score From Baseline to Week 12
Description	ACQ-6 is simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment. The 6-point self-administered scale has items measuring asthma symptoms and rescue inhaler use. The ACQ score is the mean of the questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). The original protocol planned to analyze the ACQ-7 score. As a result of FEV1 testing restrictions imposed on the study during the COVID-19 pandemic, the analysis was prospectively modified to the ACQ-6 score prior to database lock. The ACQ-6 is a validated questionnaire and is identical to the ACQ-7, with the exception of FEV1 data that is also utilized in the ACQ-7 questionnaire total score calculation.
Time Frame	Baseline, 12 Weeks

Outcome Measure Data

Analysis Population Description
The efficacy population was a modified intent-to-treat sample and consist of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who have at least one post-randomization evaluation.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	25	22	24	28
Least Squares Mean (Standard Error) [scores on a scale]	-0.391 (0.1866)	-0.419 (0.1974)	-0.437 (0.1924)	-0.655 (0.1803)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 150 mg BID Dexpramipexole
	Comments	The 150 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3059
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.264
	Confidence Interval	(2-Sided) 95% -0.772 to 0.245
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 150 mg BID dexpramipexole group compared to the placebo group in change in ACQ-6 score from Baseline to Week 12 (end of primary treatment period). A negative value indicates improvement of asthma symptoms.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 75 mg BID Dexpramipexole
	Comments	The 75 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8642
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0457
	Confidence Interval	(2-Sided) 95% -0.575 to 0.484
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 75 mg BID dexpramipexole group compared to the placebo group in change in ACQ-6 score from Baseline to Week 12 (end of primary treatment period). A negative value indicates improvement of asthma symptoms.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 37.5 mg BID Dexpramipexole
	Comments	The 37.5 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM).
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9182
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0276
	Confidence Interval	(2-Sided) 95% -0.560 to 0.505
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 37.5 mg BID dexpramipexole group compared to the placebo group in change in ACQ-6 score from Baseline to Week 12 (end of primary treatment period). A negative value indicates improvement of asthma symptoms.

4. Secondary Outcome

Title	Change in Post-bronchodilator FEV1 From Baseline to Week 12
Description	Post-bronchodilator FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation, after treatment with inhaled albuterol.
Time Frame	Baseline, 12 Weeks

Outcome Measure Data

Analysis Population Description
The efficacy population was a modified intent-to-treat sample and consist of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who have at least one post-randomization evaluation.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	20	18	22	23
Least Squares Mean (Standard Error) [liters]	-0.00546 (0.07208)	0.0932 (0.07455)	-0.000717 (0.06977)	0.176 (0.07182)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 150 mg BID Dexpramipexole
	Comments	An ANCOVA analysis was performed comparing the 150 mg BID dexpramipexole group to placebo.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0716
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.181
	Confidence Interval	(2-Sided) 95% -0.0163 to 0.378
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate the difference of the 150 mg BID Dexpramipexole group from placebo in change in post-bronchodilator FEV1 from Baseline to Week 12 (end of primary treatment period) in liters. A positive value indicates improvement in lung function.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 75 mg BID Dexpramipexole
	Comments	An ANCOVA analysis was performed comparing the 75 mg BID dexpramipexole group to placebo.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9619
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.00474
	Confidence Interval	(2-Sided) 95% -0.192 to 0.202
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate the difference of the 75 mg BID Dexpramipexole group from placebo in change in post-bronchodilator FEV1 from Baseline to Week 12 (end of primary treatment period) in liters. A positive value indicates improvement in lung function.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 37.5 mg BID Dexpramipexole
	Comments	An ANCOVA analysis was performed comparing the 37.5 mg BID dexpramipexole group to placebo.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3368
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.0987
	Confidence Interval	(2-Sided) 95% -0.105 to 0.302
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate the difference of the 37.5 mg BID Dexpramipexole group from placebo in change in post-bronchodilator FEV1 from Baseline to Week 12 (end of primary treatment period) in liters. A positive value indicates improvement in lung function.

5. Secondary Outcome

Title	Change in Quality of Life, as Measured by the Asthma Quality of Life Questionnaire (AQLQ) From Baseline to Week 12
Description	The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma. The 32 questions in the AQLQ are divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions and ranges from 1 to 7. A score 7.0 indicates that the patient has no impairments due to asthma and score 1.0 indicates severe impairment.
Time Frame	Baseline, 12 Weeks

Outcome Measure Data

Analysis Population Description
The efficacy population was a modified intent-to-treat sample and consist of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who have at least one post-randomization evaluation.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	26	22	25	28
Least Squares Mean (Standard Error) [scores on a scale]	0.376 (0.1999)	0.531 (0.2112)	0.312 (0.2055)	0.584 (0.1979)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 150 mg BID Dexpramipexole
	Comments	An ANCOVA analysis was performed comparing the 150 mg BID dexpramipexole group to placebo.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4512
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.208
	Confidence Interval	(2-Sided) 95% -0.338 to 0.755
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate the difference in the 150 mg BID dexpramipexole group from the placebo group in the change in AQLQ score from Baseline to Week 12 (end of primary treatment period). A positive value indicates improvement of asthma symptoms.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 75 mg BID Dexpramipexole
	Comments	An ANCOVA analysis was performed comparing the 75 mg BID dexpramipexole group to placebo.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8214
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0642
	Confidence Interval	(2-Sided) 95% -0.627 to 0.499
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate the difference in the 75 mg BID dexpramipexole group from the placebo group in the change in AQLQ score from Baseline to Week 12 (end of primary treatment period). A positive value indicates improvement of asthma symptoms.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 37.5 mg BID Dexpramipexole
	Comments	An ANCOVA analysis was performed comparing the 37.5 mg BID dexpramipexole group to placebo.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5894
	Comments	For secondary endpoints which were not key secondary endpoints, no adjustment for multiple testing was used and p <0.05 was used for statistical significance.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.154
	Confidence Interval	(2-Sided) 95% -0.411 to 0.720
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate the difference in the 37.5 mg BID dexpramipexole group from the placebo group in the change in AQLQ score from Baseline to Week 12 (end of primary treatment period). A positive value indicates improvement of asthma symptoms.

6. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group Post Randomization Through Week 12
Description	Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time Frame	Immediately post-baseline up to Week 12

Outcome Measure Data

Analysis Population Description
The safety population includes all subjects who were randomized and received at least one dose of study drug during the primary treatment period.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	27	22	26	28
Eosinophils >1.6 x 10^9/L	0 0%	0 0%	0 0%	0 0%
Basophils >1.6 x 10^9/L	0 0%	0 0%	0 0%	0 0%
Erythrocytes ≤3.5 x 10^12/L	0 0%	1 4.5%	0 0%	2 7.1%
Erythrocytes ≥6.4 x 10^12/L	0 0%	0 0%	0 0%	0 0%
Hematocrit ≤32% - Females	0 0%	2 9.1%	0 0%	1 3.6%
Hematocrit ≥54% - Females	0 0%	0 0%	0 0%	0 0%
Hematocrit ≤37% - Males	2 7.4%	0 0%	1 3.8%	1 3.6%
Hematocrit ≥60% - Males	0 0%	0 0%	0 0%	0 0%
Hemoglobin ≤9.5 g/dL - Females	0 0%	1 4.5%	0 0%	0 0%
Hemoglobin ≥17.5 g/dL - Females	0 0%	0 0%	0 0%	0 0%
Hemoglobin ≤11.5 g/dL - Males	2 7.4%	0 0%	0 0%	1 3.6%
Hemoglobin ≥19.0 g/dL - Males	0 0%	0 0%	0 0%	0 0%
Leukocytes <3.0 x 10^9/L	0 0%	0 0%	0 0%	1 3.6%
Leukocytes ≥16 x 10^9/L	0 0%	1 4.5%	0 0%	1 3.6%
Lymphocytes <0.8 x 10^9/L	0 0%	0 0%	0 0%	1 3.6%
Lymphocytes >12 x 10^9/L	0 0%	0 0%	0 0%	0 0%
Monocytes >2.5 x 10^9/L	0 0%	0 0%	0 0%	0 0%
Neutrophils <1.5 x 10^9/L	1 3.7%	1 4.5%	1 3.8%	1 3.6%
Neutrophils ≥13.5 x 10^9/L	0 0%	0 0%	0 0%	0 0%
Platelets ≤75 x 10^9/L	0 0%	0 0%	0 0%	0 0%
Platelets ≥700 x 10^9/L	0 0%	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group Post Randomization Through Week 12
Description	Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time Frame	Immediately post-baseline up to Week 12

Outcome Measure Data

Analysis Population Description
The safety population includes all subjects who were randomized and received at least one dose of study drug during the primary treatment period.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	27	22	26	28
ALT ≥ 3 x ULN	0 0%	0 0%	1 3.8%	0 0%
Albumin ≤ 2.5 g/dL	0 0%	0 0%	0 0%	0 0%
Alkaline Phosphatase ≥ 1.5 x ULN	0 0%	0 0%	1 3.8%	1 3.6%
AST ≥ 3 x ULN	0 0%	0 0%	0 0%	0 0%
Bicarbonate ≤ 16 mEq/L	0 0%	0 0%	1 3.8%	0 0%
Bicarbonate ≥ 35 mEq/L	0 0%	0 0%	0 0%	0 0%
Bilirubin > 2 X ULN and (ALT or AST ≥ 3 X ULN)	0 0%	0 0%	0 0%	0 0%
Bilirubin ≥ 1.5 x ULN	0 0%	0 0%	0 0%	0 0%
Calcium ≤ 8 mg/dL	0 0%	2 9.1%	0 0%	3 10.7%
Calcium ≥ 12 mg/dL	0 0%	0 0%	0 0%	0 0%
Chloride ≤ 90 mEq/L	0 0%	0 0%	0 0%	0 0%
Chloride ≥ 118 mEq/L	0 0%	0 0%	0 0%	0 0%
Creatinine ≥ 2 mg/dL - Females	0 0%	0 0%	0 0%	0 0%
Creatinine ≥ 2 mg/dL - Males	0 0%	0 0%	0 0%	0 0%
Glucose ≤ 39.6 mg/dL	0 0%	0 0%	0 0%	0 0%
Glucose ≥ 175 mg/dL	2 7.4%	2 9.1%	1 3.8%	1 3.6%
Magnesium ≤ 1.2 mg/dL	0 0%	1 4.5%	0 0%	1 3.6%
Magnesium ≥ 2.9 mg/dL	0 0%	0 0%	0 0%	0 0%
Phosphate ≤ 1.86 mg/dL	0 0%	0 0%	0 0%	0 0%
Phosphate ≥ 5.27 mg/dL	0 0%	0 0%	0 0%	0 0%
Potassium ≤ 3 mEq/L	0 0%	0 0%	0 0%	0 0%
Potassium ≥ 6 mEq/L	0 0%	0 0%	0 0%	0 0%
Protein [Serum] ≤ 4.5 g/dL	0 0%	0 0%	0 0%	0 0%
Protein [Serum] ≥ 10 g/dL	0 0%	0 0%	0 0%	0 0%
Sodium ≤ 126 mEq/L	0 0%	0 0%	0 0%	0 0%
Sodium ≥ 156 mEq/L	0 0%	0 0%	0 0%	0 0%
Urate ≥ 8.5 mg/dL - Females	0 0%	0 0%	0 0%	1 3.6%
Urate ≥ 10.5 mg/dL - Males	0 0%	0 0%	0 0%	0 0%
Urea Nitrogen ≥ 30 mg/dL	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Urinalysis Results by Treatment Group Post Randomization Through Week 12
Description	Number of Participants with Potentially Clinically Significant Urinalysis Results (glycosuria, ketonuria, or proteinuria) by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline urinalysis value in each treatment group. Patients are only counted once per criterion per laboratory test. The number of participants with potential clinical important urinalysis findings at any post-baseline visit were reported.
Time Frame	Immediately post-baseline up to Week 12

Outcome Measure Data

Analysis Population Description
The safety population includes all subjects who were randomized and received at least one dose of study drug during the primary treatment period.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	27	22	26	28
glycosuria (glucose in urine ++++)	1 3.7%	2 9.1%	1 3.8%	0 0%
ketonuria (ketones in urine ≥ ++++)	0 0%	0 0%	0 0%	0 0%
proteinuria (protein in urine ≥ ++)	1 3.7%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Vital Signs Results by Treatment Group Post Randomization Through Week 12
Description	Number of Participants with Potentially Clinically Significant Vital Signs Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time Frame	Immediately post-baseline up to Week 12

Outcome Measure Data

Analysis Population Description
The safety population includes all subjects who were randomized and received at least one dose of study drug during the primary treatment period.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	27	22	26	28
Systolic blood pressure: >180 mmHg	0 0%	0 0%	0 0%	0 0%
Systolic blood pressure: Increase >40 mmHg	0 0%	0 0%	0 0%	0 0%
Systolic blood pressure: <90 mmHg	0 0%	0 0%	0 0%	0 0%
Systolic blood pressure: Decrease >30 mmHg	0 0%	0 0%	0 0%	0 0%
Diastolic blood pressure: >105 mmHg	0 0%	0 0%	0 0%	0 0%
Diastolic blood pressure: Increase >30 mmHg	0 0%	1 4.5%	0 0%	0 0%
Diastolic blood pressure: <50 mmHg	0 0%	0 0%	0 0%	0 0%
Diastolic blood pressure: Decrease >20 mmHg	0 0%	0 0%	0 0%	0 0%
Pulse: >120 bpm	0 0%	0 0%	0 0%	0 0%
Pulse: Increase >30 bpm	0 0%	0 0%	0 0%	0 0%
Pulse: <50 bpm	0 0%	1 4.5%	0 0%	0 0%
Pulse: Decrease >20 bpm	0 0%	0 0%	1 3.8%	1 3.6%
Temperature: >38.5°C and an increase ≥1°C	0 0%	0 0%	0 0%	0 0%
Body weight: Increase ≥7% from Baseline	0 0%	0 0%	1 3.8%	1 3.6%
Body weight: Decrease ≥7% from Baseline	0 0%	0 0%	0 0%	1 3.6%

10. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant ECG Results by Treatment Group Post Randomization Through Week 12
Description	Number of Participants with Potentially Clinically Significant ECG Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time Frame	Immediately post-baseline up to Week 12

Outcome Measure Data

Analysis Population Description
The safety population includes all subjects who were randomized and received at least one dose of study drug during the primary treatment period.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	27	22	26	28
Heart Rate >120 bpm	0 0%	0 0%	0 0%	0 0%
Heart Rate Increase from Baseline >30 bpm	0 0%	0 0%	0 0%	1 3.6%
QT Interval: >450 ms	0 0%	0 0%	0 0%	0 0%
QT Interval: >480 ms	0 0%	0 0%	0 0%	0 0%
QT Interval: >500 ms	0 0%	0 0%	0 0%	0 0%
QT Interval: Increase from Baseline >30 ms	7 25.9%	3 13.6%	2 7.7%	0 0%
QT Interval: Increase from Baseline >60 ms	0 0%	0 0%	0 0%	0 0%
QTcF Interval: >450 ms	0 0%	0 0%	0 0%	0 0%
QTcF Interval: >480 ms	0 0%	0 0%	0 0%	0 0%
QTcF Interval: >500 ms	0 0%	0 0%	0 0%	0 0%
QTcF Interval: Increase from Baseline >30 ms	1 3.7%	0 0%	0 0%	0 0%
QTcF Interval: Increase from Baseline >60 ms	0 0%	0 0%	0 0%	0 0%
Change from Baseline in PR >25% and PR value >220 ms	0 0%	0 0%	0 0%	0 0%
Change from Baseline in QRS >25% and QRS value >110 ms	0 0%	0 0%	0 0%	0 0%

11. Other Pre-specified Outcome

Title	Change in Nasal Eosinophil Peroxidase (Presented as Ratio to Protein) From Baseline to Week 12
Description	The EPX:protein ratio was used to normalize the EPX for the quantity of sample, yielding the values in ng EPX per mg protein. The ratio of nasal Eosinophil Peroxidase to Protein is a biomarker for airway eosinophils. A lower ratio to Baseline represents a lowering in airway eosinophilia, which is a marker of successful drug therapy.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description
The efficacy population was a modified intent-to-treat sample and consists of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who had both Baseline (non-zero) and Week 12 values.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	15	16	19	19
Median (Inter-Quartile Range) [ratio to baseline]	0.833	0.645	0.174	0.110

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 150 mg BID Dexpramipexole
	Comments	The 150 mg BID dexpramipexole group was compared to placebo at Week 12 using a Wilcoxon rank sum test.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0196
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 75 mg BID Dexpramipexole
	Comments	The 75mg BID dexpramipexole group was compared to placebo at Week 12 using a Wilcoxon rank sum test.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0207
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 37.5 mg BID Dexpramipexole
	Comments	The 37.5 mg BID dexpramipexole group was compared to placebo at Week 12 using a Wilcoxon rank sum test.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5399
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Wilcoxon (Mann-Whitney)
	Comments

12. Other Pre-specified Outcome

Title	Change in Blood Absolute Blood Basophil Count From Baseline to Week 12
Description	The analysis used a mixed effects model repeated-measures MMRM with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value. Basophils were enumerated as part of the WBC automated differential performed by the Central Laboratory.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description
The efficacy population was a modified intent-to-treat sample and consists of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who have at least one post-randomization evaluation.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	25	22	24	28
Least Squares Mean (Standard Error) [cells (10*9/L)]	-0.00439 (0.006323)	-0.00655 (0.006674)	-0.0250 (0.006487)	-0.0277 (0.006082)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 150 mg BID Dexpramipexole
	Comments	The 150 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM) with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0084
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0233
	Confidence Interval	(2-Sided) 95% -0.0405 to -0.00613
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 150 mg BID group from the placebo group in the change absolute basophil count (automated differential) from Baseline to Week 12 (end of primary treatment period). A negative value represents fewer basophils.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 75 mg BID Dexpramipexole
	Comments	The 75 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM) with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0237
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0206
	Confidence Interval	(2-Sided) 95% -0.0384 to -0.00281
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 75 mg BID group from the placebo group in the change absolute basophil count (automated differential) from Baseline to Week 12 (end of primary treatment period). A negative value represents fewer basophils.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 37.5 mg BID Dexpramipexole
	Comments	The 37.5 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM) with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8140
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.00215
	Confidence Interval	(2-Sided) 95% -0.0203 to 0.0160
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 37.5 mg BID group from the placebo group in the change absolute basophil count (automated differential) from Baseline to Week 12 (end of primary treatment period). A negative value represents fewer basophils.

13. Other Pre-specified Outcome

Title	Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 12
Description	FeNO is non-invasive biomarker of airway inflammation in asthma participants.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description
The efficacy population was a modified intent-to-treat sample and consists of all subjects in the safety population (all subjects who were randomized and received at least one dose of randomized study drug) and who have at least one post-randomization evaluation.

Arm/Group Title	Placebo BID	37.5 mg BID Dexpramipexole	75 mg BID Dexpramipexole	150 mg BID Dexpramipexole
Arm/Group Description	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. Placebo: placebo twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks	Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. Dexpramipexole: dexpramipexole twice daily oral dosing for up to 12 weeks
Measure Participants	17	17	20	23
Least Squares Mean (Standard Error) [parts per billion]	3.38 (4.6447)	-6.79 (4.7849)	-3.14 (4.3651)	-4.86 (4.2175)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 150 mg BID Dexpramipexole
	Comments	The 150 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM) with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1886
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.24
	Confidence Interval	(2-Sided) 95% -20.6 to 4.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 150 mg BID group from the placebo group in the change in FeNO from Baseline to Week 12 in liters. In eosinophilic asthma, a lower FeNO indicates less eosinophilic inflammation of the airway than a higher value.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 75 mg BID Dexpramipexole
	Comments	The 75mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM) with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3061
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.53
	Confidence Interval	(2-Sided) 95% -19.1 to 6.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 75 mg BID group from the placebo group in the change in FeNO from Baseline to Week 12 in liters. In eosinophilic asthma, a lower FeNO indicates less eosinophilic inflammation of the airway than a higher value.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, 37.5 mg BID Dexpramipexole
	Comments	The 37.5 mg BID dexpramipexole group was compared to placebo using a mixed effects model repeated-measures (MMRM) with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1294
	Comments	No adjustment for multiple testing of exploratory endpoints was used.
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.2
	Confidence Interval	(2-Sided) 95% -23.4 to 3.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimate is the difference of the 37.5 mg BID group from the placebo group in the change in FeNO from Baseline to Week 12 in liters. In eosinophilic asthma, a lower FeNO indicates less eosinophilic inflammation of the airway than a higher value.

Adverse Events

	Screening Period		Primary Assessment Period: Placebo BID		Primary Assessment Period: 37.5 mg BID		Primary Assessment Period: 75 mg BID		Primary Assessment Period: 150 mg BID		Eosinophil Recovery Period: Assigned to Placebo BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 37.5 mg BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 75 mg BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 150 mg BID During Primary Assessment Period
Time Frame	Placebo Run-in Period = from enrollment to Randomization (2-4 weeks); Primary Assessment Period = from Randomization through the Week 12 visit, plus 30 days following the last dose; Eosinophil Recovery Period = all visits occurring from 30 days following the last dose through the end of study (Week 24 post-Randomization)
Adverse Event Reporting Description

Arm/Group Title	Screening Period		Primary Assessment Period: Placebo BID		Primary Assessment Period: 37.5 mg BID		Primary Assessment Period: 75 mg BID		Primary Assessment Period: 150 mg BID		Eosinophil Recovery Period: Assigned to Placebo BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 37.5 mg BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 75 mg BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 150 mg BID During Primary Assessment Period
Arm/Group Description	All subjects who signed informed consent and entered the Primary Assessment Period		Following the 2-4 week placebo Run-in Period, randomized subjects continued to receive 1 tablet placebo twice daily for 12 weeks during the Primary Assessment Period. Placebo: 1 placebo tablet twice daily		Following the 2-4 week placebo Run-in Period, randomized subjects received 1 tablet dexpramipexole 37.5 mg twice daily for 12 weeks during the Primary Assessment Period. Dexpramipexole: 1 dexpramipexole tablet twice daily		Following the 2-4 week placebo Run-in Period, randomized subjects received 1 tablet dexpramipexole 75 mg twice daily for 12 weeks during the Primary Assessment Period. Dexpramipexole: 1 dexpramipexole tablet twice daily		Following the 2-4 week placebo Run-in Period, randomized subjects received 1 tablet dexpramipexole 150 mg twice daily for 12 weeks during the Primary Assessment Period. Dexpramipexole: 1 dexpramipexole tablet twice daily		Following the Primary Assessment Period, subjects were followed within their randomized treatment group		Following the Primary Assessment Period, subjects were followed within their randomized treatment group		Following the Primary Assessment Period, subjects were followed within their randomized treatment group		Following the Primary Assessment Period, subjects were followed within their randomized treatment group
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Serious Adverse Events
	Screening Period		Primary Assessment Period: Placebo BID		Primary Assessment Period: 37.5 mg BID		Primary Assessment Period: 75 mg BID		Primary Assessment Period: 150 mg BID		Eosinophil Recovery Period: Assigned to Placebo BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 37.5 mg BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 75 mg BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 150 mg BID During Primary Assessment Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Screening Period		Primary Assessment Period: Placebo BID		Primary Assessment Period: 37.5 mg BID		Primary Assessment Period: 75 mg BID		Primary Assessment Period: 150 mg BID		Eosinophil Recovery Period: Assigned to Placebo BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 37.5 mg BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 75 mg BID During Primary Assessment Period		Eosinophil Recovery Period: Assigned to 150 mg BID During Primary Assessment Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/103 (5.8%)		9/27 (33.3%)		7/22 (31.8%)		12/26 (46.2%)		12/28 (42.9%)		2/25 (8%)		3/22 (13.6%)		5/24 (20.8%)		10/28 (35.7%)
Blood and lymphatic system disorders
Monocytopenia	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Neutropenia	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Congenital, familial and genetic disorders
Sinus Bradycardia	1/103 (1%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Ear and labyrinth disorders
Ear pain	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/103 (1%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Aphthous ulcer	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Dry mouth	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Gastrooesophageal reflux disease	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Vomiting	0/103 (0%)		0/27 (0%)		1/22 (4.5%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Nausea	0/103 (0%)		0/27 (0%)		0/22 (0%)		2/26 (7.7%)		0/28 (0%)		0/25 (0%)		1/22 (4.5%)		0/24 (0%)		0/28 (0%)
General disorders
Chest discomfort	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Fatigue	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Peripheral swelling	1/103 (1%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Hepatobiliary disorders
Cholecystitis	0/103 (0%)		0/27 (0%)		1/22 (4.5%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Immune system disorders
Anaphylactic reaction	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Infections and infestations
Acute sinusitis	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Bronchitis	0/103 (0%)		0/27 (0%)		1/22 (4.5%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Corona virus infection	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Ear infection fungal	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Influenza	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		2/28 (7.1%)
Nasopharyngitis	0/103 (0%)		1/27 (3.7%)		3/22 (13.6%)		0/26 (0%)		1/28 (3.6%)		1/25 (4%)		0/22 (0%)		1/24 (4.2%)		0/28 (0%)
Otitis externa	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Sinusitis	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Upper respiratory tract infection	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		2/26 (7.7%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		1/24 (4.2%)		0/28 (0%)
Urethritis	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Viral upper respiratory tract infection	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Injury, poisoning and procedural complications
Contusion	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Fall	1/103 (1%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Foreign body in ear	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Scratch	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		1/24 (4.2%)		0/28 (0%)
Skin laceration	0/103 (0%)		0/27 (0%)		1/22 (4.5%)		1/26 (3.8%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Sunburn	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Tooth fracture	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Eye contusion	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		1/22 (4.5%)		0/24 (0%)		0/28 (0%)
Soft tissue injury	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		1/22 (4.5%)		0/24 (0%)		0/28 (0%)
Investigations
Coronavirus test positive	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		2/28 (7.1%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Metabolism and nutrition disorders
Fluid retention	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Diabetes mellitus	1/103 (1%)		0/27 (0%)		1/22 (4.5%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		1/22 (4.5%)		0/24 (0%)		0/28 (0%)
Hypomagnesaemia	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		1/22 (4.5%)		0/24 (0%)		0/28 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		1/25 (4%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Back pain	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		2/28 (7.1%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Intervertebral disc protrusion	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Muscle twitching	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Musculoskeletal pain	0/103 (0%)		0/27 (0%)		1/22 (4.5%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Neck pain	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Pain in extremity	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		2/26 (7.7%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		1/24 (4.2%)		0/28 (0%)
Nervous system disorders
Headache	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Migraine	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		1/28 (3.6%)
Tension headache	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		1/22 (4.5%)		0/24 (0%)		0/28 (0%)
Psychiatric disorders
Depression	1/103 (1%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Insomnia	1/103 (1%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/103 (0%)		2/27 (7.4%)		2/22 (9.1%)		0/26 (0%)		2/28 (7.1%)		1/25 (4%)		1/22 (4.5%)		0/24 (0%)		2/28 (7.1%)
Cough	1/103 (1%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		1/24 (4.2%)		0/28 (0%)
Dyspnoea	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Nasal congestion	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		1/24 (4.2%)		0/28 (0%)
Oropharyngeal pain	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Rhinitis allergic	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Sinus congestion	0/103 (0%)		1/27 (3.7%)		0/22 (0%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/103 (0%)		0/27 (0%)		1/22 (4.5%)		0/26 (0%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Pruritus	0/103 (0%)		0/27 (0%)		0/22 (0%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Rash	0/103 (0%)		0/27 (0%)		1/22 (4.5%)		1/26 (3.8%)		0/28 (0%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)
Vascular disorders
Hypertension	0/103 (0%)		0/27 (0%)		0/22 (0%)		0/26 (0%)		1/28 (3.6%)		0/25 (0%)		0/22 (0%)		0/24 (0%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Knopp's agreements with its investigators may vary. However, Knopp does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial, and are subject to a minimum 60 day review period by Knopp.

Results Point of Contact

Name/Title	Vice President, Clinical and Translational Medicine
Organization	Knopp Biosciences
Phone	4124881776
Email	calman@knoppbio.com

Responsible Party:

Knopp Biosciences

ClinicalTrials.gov Identifier:

NCT04046939

Other Study ID Numbers:

KNS-760704-AS201

First Posted:

Aug 6, 2019

Last Update Posted:

Mar 28, 2022

Last Verified:

Feb 1, 2022

AS201: Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Other Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Certain Agreements

Results Point of Contact