Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma

NCT04046939 | Completed Phase 2 Results FDA Drug

• 1 other identifier: KNS-760704-AS201
• Study Type: interventional
• Target: 534
• Locations: 1 country
• Sites: 36

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.

Conditions

Eosinophilic Asthma; Asthma

Keywords

Eosinophilic Asthma; Asthma; dexpramipexole

Outcome Measures

Primary Outcomes (1)

• Change in Blood Absolute Eosinophil Count From Baseline to Week 12

  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.

  Baseline, 12 Weeks

Secondary Outcomes (9)

• Change in Pre-bronchodilator FEV1 (Liters) From Baseline to Week 12

  Baseline, 12 Weeks

• Change in Asthma Control Questionnaire (ACQ-6) Score From Baseline to Week 12

  Baseline, 12 Weeks

• Change in Post-bronchodilator FEV1 From Baseline to Week 12

  Baseline, 12 Weeks

• Change in Quality of Life, as Measured by the Asthma Quality of Life Questionnaire (AQLQ) From Baseline to Week 12

  Baseline, 12 Weeks

• Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group Post Randomization Through Week 12

  Immediately post-baseline up to Week 12

Other Outcomes (3)

• Change in Nasal Eosinophil Peroxidase (Presented as Ratio to Protein) From Baseline to Week 12

  Baseline, Week 12

• Change in Blood Absolute Blood Basophil Count From Baseline to Week 12

  Baseline, Week 12

• Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 12

  Baseline, Week 12

Study Arms (4)

placebo BID

PLACEBO COMPARATOR

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks.

Drug: Placebo

37.5 mg BID dexpramipexole

ACTIVE COMPARATOR

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

75 mg BID dexpramipexole

ACTIVE COMPARATOR

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks.

Drug: Dexpramipexole

150 mg BID dexpramipexole

ACTIVE COMPARATOR

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks.

Drug: Dexpramipexole

Interventions

Dexpramipexole DRUG

dexpramipexole twice daily oral dosing for up to 12 weeks

Also known as: KNS-760704, BIIB050

150 mg BID dexpramipexole; 37.5 mg BID dexpramipexole; 75 mg BID dexpramipexole

Placebo DRUG

placebo twice daily oral dosing for up to 12 weeks

Also known as: PBO

placebo BID

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Knopp Biosciences: lead

Study Sites (36)

Research Site

Los Angeles, California, 90048, United States

Location

Research Site

Mission Viejo, California, 92691, United States

Location

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Westminster, California, 92683, United States

Location

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Denver, Colorado, 80230, United States

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Daytona Beach, Florida, 32117, United States

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Miami, Florida, 33186, United States

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Orlando, Florida, 32803, United States

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Tampa, Florida, 33612, United States

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Tampa, Florida, 33634, United States

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Lawrenceville, Georgia, 30046, United States

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Winder, Georgia, 30680, United States

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Boise, Idaho, 83706, United States

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Farmington Hills, Michigan, 48336, United States

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Plymouth, Minnesota, 55441, United States

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St Louis, Missouri, 63110, United States

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St Louis, Missouri, 63141, United States

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Las Vegas, Nevada, 89119, United States

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New Brunswick, New Jersey, 08901, United States

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Corning, New York, 14830, United States

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New Hyde Park, New York, 11042, United States

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Raleigh, North Carolina, 27607, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45231, United States

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Cincinnati, Ohio, 45242, United States

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Columbus, Ohio, 43235, United States

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Dublin, Ohio, 43016, United States

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Edmond, Oklahoma, 73034, United States

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Medford, Oregon, 97504, United States

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Portland, Oregon, 97202, United States

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Pittsburgh, Pennsylvania, 15205, United States

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Anderson, South Carolina, 29621, United States

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North Charleston, South Carolina, 29406, United States

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Allen, Texas, 75013, United States

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Boerne, Texas, 78006, United States

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Dallas, Texas, 75240, United States

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El Paso, Texas, 79902, United States

Location

MeSH Terms

Conditions

Pulmonary Eosinophilia; Asthma

Interventions

Dexpramipexole

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Vice President, Clinical and Translational Medicine
• Organization: Knopp Biosciences

calman@knoppbio.com

4124881776

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Four-arm parallel assignment

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: August 6, 2019
• Study Start: August 15, 2019
• Primary Completion: December 3, 2020
• Study Completion: March 2, 2021
• Last Updated: April 13, 2023
• Results First Posted: December 22, 2021

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (36)