Dexpramipexole for Asthma

(EXHALE-5 Trial)

Recruiting at 62 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Areteia Therapeutics

Must be taking: Step 4 or 5 asthma therapy

Must not be taking: Neutropenia risk drugs

Disqualifiers: Pregnancy, Breastfeeding, Allergy to dexpramipexole, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 16

Duration: 52 weeks

1600 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that treatment with certain drugs known to cause neutropenia (a condition where you have a low number of white blood cells) in the past 30 days is not allowed.

Is Dexpramipexole safe for humans?

There is no specific safety data available for Dexpramipexole in the provided research articles. ^{1 2 3 4 5}

Research Team

Sady Alpizar, MD

Principal Investigator

Clinical Research Trials of Florida, Inc.

Eligibility Criteria

This trial is for people aged 12 or older with severe asthma who are already on high-level asthma treatments (GINA Step 4 or 5) and have completed the EXHALE-2 or EXHALE-3 studies. It's not specified who can't join, but typically there would be criteria to exclude those with other health issues that could affect results.

Inclusion Criteria

Participants who completed the double-blind study intervention treatment period during either of the Phase III studies EXHALE-2 or EXHALE-3

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

Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Baseline Visit/Day 1

Exclusion Criteria

Participants with allergy/intolerance to dexpramipexole or any of its excipients

Pregnant or breastfeeding women

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexpramipexole 150 mg oral tablet twice a day to evaluate long-term safety and tolerability

52 weeks

Visits at baseline, Weeks 16, 32, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Dexpramipexole Dihydrochloride

Trial Overview The study tests the long-term safety of a drug called Dexpramipexole Dihydrochloride in individuals with severe asthma. Participants from previous Phase III trials will continue treatment to gather more data on its effects over an extended period.

Participant Groups

Group I: 150 mg BID Experimental Treatment 1 Intervention

Dexpramipexole 150 mg oral tablet taken twice a day.

Who Is Running the Clinical Trial?

Areteia Therapeutics

Lead Sponsor

Trials

5

Recruited

4,500+

Findings from Research

RP 49356 is a novel potassium channel opener that effectively relaxes airway smooth muscle in vitro, similar to another compound, cromakalim, and works by opening sulphonylurea-sensitive K+ channels.

The compound shows greater potency in relaxing airway tissues that are already contracted (spasmolytic effects) rather than preventing contraction from spasmogens, indicating its potential use in treating conditions with airway constriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RP 49356 and cromakalim relax airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel: a comparison with nifedipine. Raeburn, D., Brown, TJ.[2014]

BRL 38227 (lemakalim), a selective K+ channel activator, effectively relaxes human airway smooth muscle in vitro, achieving 60-80% of the relaxation efficacy of isoproterenol, with an EC50 of 0.2 to 0.6 microM against various spasmogens.

The relaxation effect of BRL 38227 is significantly inhibited by the ATP-sensitive K+ channel antagonist glibenclamide, confirming its mechanism of action through K+ channels, and it can provide additional relaxation even when calcium channels are blocked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The action of a potassium channel activator, BRL 38227 (lemakalim), on human airway smooth muscle. Black, JL., Armour, CL., Johnson, PR., et al.[2014]

In a study involving eight mild asthmatic subjects, both nedocromil sodium and sodium cromoglycate significantly protected against bradykinin-induced bronchoconstriction, indicating their potential efficacy in managing asthma symptoms.

The study suggests that these medications may act on neural pathways involved in bronchoconstriction, providing insight into their mechanism of action in asthma control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate. Dixon, CM., Barnes, PJ.[2019]

In a study involving 12 adult patients with mild to moderate asthma, inhaled bimakalim did not demonstrate any bronchodilator effect at cumulative doses up to 175 micrograms, suggesting it may not be effective for this purpose.

Despite the lack of efficacy, inhaled bimakalim was well tolerated, with no reported side effects such as headache or cardiovascular events during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The lack of bronchodilator effect and the short-term safety of cumulative single doses of an inhaled potassium channel opener (bimakalim) in adult patients with mild to moderate bronchial asthma. Faurschou, P., Mikkelsen, KL., Steffensen, I., et al.[2019]

In a study involving 23 patients with nocturnal asthma, a single dose of 0.5 mg cromakalim significantly reduced the early morning drop in lung function (FEV1) compared to placebo, indicating its potential efficacy in managing nocturnal asthma symptoms.

In a follow-up study with 8 asthmatic subjects, repeated doses of cromakalim (0.25 mg and 0.5 mg) over 5 nights further decreased the early morning FEV1 decline, suggesting that potassium-channel activators could be beneficial for long-term asthma management, particularly for nighttime symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuation of nocturnal asthma by cromakalim. Williams, AJ., Lee, TH., Cochrane, GM., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

RP 49356 and cromakalim relax airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel: a comparison with nifedipine. [2014]

2. United States pubmed.ncbi.nlm.nih.gov

The action of a potassium channel activator, BRL 38227 (lemakalim), on human airway smooth muscle. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The lack of bronchodilator effect and the short-term safety of cumulative single doses of an inhaled potassium channel opener (bimakalim) in adult patients with mild to moderate bronchial asthma. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Attenuation of nocturnal asthma by cromakalim. [2019]