Phase III Long-Term Extension Study With Dexpramipexole (EXHALE-5)

An Open-Label Long-Term Phase III Extension Study to Assess the Long-Term Safety and Tolerability of Dexpramipexole in Participants With Severe Eosinophilic Asthma

The goal of this clinical trial] is to evaluate the long term safety of dexpramipexole treatment in participants with severe asthma, aged ≥12 years, on Global Initiative for Asthma (GINA) 2021 [GINA, 2021] Step 4 or 5 therapy and who completed either of the Phase III studies EXHALE-2 or EXHALE-3.

Study Overview

• Status: Enrolling by invitation
• Conditions: Eosinophilic Asthma
• Intervention / Treatment: Drug: Dexpramipexole Dihydrochloride

• Study Type: Interventional
• Enrollment (Estimated): 1600
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33607
      • Research Site 20001-004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants who completed the double-blind study intervention treatment period during either of the Phase III studies EXHALE-2 or EXHALE-3.
2. Participants capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
3. Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Baseline Visit/Day 1.

4. WOCBP (after menarche) must use either of the following methods of birth control, from the Baseline Visit/Day 1 through the End of Study Visit:

   1. A highly effective form of birth control (confirmed by the investigator). Highly effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective intrauterine device (IUD), IUD/intrauterine system, levonorgestrel intrauterine system, or oral contraceptive. -OR-
   2. Two protocol acceptable methods of contraception in tandem. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for ≥12 months prior to the planned date of the Baseline Visit/Day 1 without an alternative medical cause. The following age specific requirements apply:
   3. Women <50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range.
   4. Women ≥50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.

Exclusion Criteria:

1. Clinically significant change in health status during either of the Phase III studies EXHALE-2 or EXHALE-3 which in the opinion of the investigator would make the participant unsuitable for participation in this study.
2. Participants with allergy/intolerance to dexpramipexole or any of its excipients.
3. Participants who met permanent discontinuation criteria or permanently discontinued study treatment for any reason in either of the Phase III studies EXHALE-2 or EXHALE-3..
4. Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days.
5. Pregnant or breastfeeding women.
6. Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 150 mg BID; Dexpramipexole 150 mg oral tablet taken twice a day.	Drug: Dexpramipexole Dihydrochloride; Oral administration of dexpramipexole tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants with a Treatment Emergent Adverse Event	Summary of participants from the safety population who experienced an adverse event.	52 weeks
Number and Percentage of Participants with Potentially Clinically Significant Postbaseline Changes in Clinical Laboratory Evaluations	Summary of participants from the safety population who experienced potentially clinically significant postbaseline changes in hematology and chemistry results.	52 weeks
Number and Percentage of Participants with Potentially Clinically Significant Postbaseline Changes in Vital Signs and Body Weight	Summary of participants from the safety population who experienced potentially clinically significant postbaseline changes in vital signs (blood pressure, pulse rate, respiratory rate, and temperature) or body weight.	52 weeks
Number and Percentage of Participants with Potentially Significant Postbaseline Changes in Electrocardiogram Parameters	Summary of participants from the safety population who experienced potentially significant postbaseline changes in electrocardiogram parameters: heart rate, PR, QRS and QTcF intervals.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe Asthma Exacerbations	Annualized rate of severe asthma exacerbations over 52 weeks	Averaged across 52 weeks
Change in Asthma Control Questionnaire-6 (ACQ-6)	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).	Day 1 (baseline), Weeks 16, 32, and 52
Change in absolute eosinophil counts (AEC)	Change from baseline, at Weeks 16, 32, and 52.	Day 1 (baseline), Weeks 16, 32, and 52

Collaborators and Investigators

• Sponsor: Areteia Therapeutics
• Investigators: Principal Investigator: Sady Alpizar, MD, Clinical Research Trials of Florida, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 8, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Severe Asthma; Uncontrolled Asthma; Exacerbations; Asthma Attack; EXHALE-4; EXHALE-2; EXHALE-3
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Leukocyte Disorders; Eosinophilia; Hypereosinophilic Syndrome; Asthma; Pulmonary Eosinophilia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole; Dexpramipexole
• Other Study ID Numbers: AR-DEX-22-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No