Dexpramipexole for Asthma

(EXHALE-5 Trial)

Not currently recruiting at 115 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new asthma medication called dexpramipexole. The goal is to evaluate its long-term effects on individuals with severe asthma who participated in previous studies of this drug. Participants must have severe asthma, currently manage it with specific treatments, and have completed earlier related studies. The trial requires taking dexpramipexole tablets twice daily. Participants should not have experienced significant health changes or allergies to the medication. As a Phase 3 trial, this study is the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment for severe asthma.

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 there any evidence suggesting that dexpramipexole is likely to be safe for humans?

Research has shown that dexpramipexole is generally safe for people with asthma. Studies have found that it reduces high levels of eosinophils, which are linked to certain types of asthma, without causing major side effects. Participants in earlier studies handled the treatment well, and no serious safety problems were reported. Since this trial is in a later phase, earlier research has demonstrated the treatment's safety for humans. Overall, current evidence suggests that dexpramipexole's safety for asthma patients looks promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Dexpramipexole is unique because it offers a novel approach to treating asthma by targeting eosinophils, which are inflammatory cells often involved in asthma symptoms. Unlike standard treatments like inhaled corticosteroids and bronchodilators that primarily focus on reducing inflammation and opening airways, dexpramipexole works by reducing the number of eosinophils in the blood. This targeted mechanism has the potential to improve asthma control, especially for patients who struggle with severe forms of the condition. Researchers are excited about this treatment because it could offer a new option for those who don't respond well to existing therapies.

What evidence suggests that dexpramipexole might be an effective treatment for asthma?

Research shows that dexpramipexole, which participants in this trial will receive, can reduce eosinophils, a type of white blood cell that can worsen asthma symptoms. Studies have found that patients generally tolerate dexpramipexole well. It offers a pill option for people with severe asthma who haven't found relief with other treatments. Previous patients experienced better asthma control with dexpramipexole. While more research is needed, these results suggest it could help manage severe asthma symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

Sady Alpizar, MD

Principal Investigator

Clinical Research Trials of Florida, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37277072/

Safety and Efficacy of Dexpramipexole in Eosinophilic ... Conclusions: Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand the ...

2. jacionline.org jacionline.org/article/S0091-6749(23)00709-1/fulltext

Safety and Efficacy of Dexpramipexole in Eosinophilic ... We sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05763121

NCT05763121 | A Study to Assess the Effect of ... This study will assess the efficacy and safety of dexpramipexole as an adjunctive oral therapy in participants with inadequately controlled asthma with an ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05813288

NCT05813288 | A Study to Assess the Effect of ... The objective of this clinical study is to investigate the safety, tolerability, and efficacy of dexpramipexole in participants with inadequately controlled ...

5. aaaai.org aaaai.org/tools-for-the-public/latest-research-summaries/the-journal-of-allergy-and-clinical-immunology/2023-the-journal-of-allergy-and-clinical-immunolog/dexpramipexole

Dexpramipexole: a new oral treatment for asthma? Results from the EXHALE trial show that dexpramipexole effectively lowers eosinophils and is well tolerated. As a well-tolerated oral treatment, ...

6. areteiatx.com areteiatx.com/documents/PIIS0091674923007091-3.pdf

Safety and Efficacy of Dexpramipexole in Eosinophilic ... Objective: We sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma.

7. empr.com empr.com/news/oral-dexpramipexole-improves-lung-function-in-eosinophilic-asthma/

Oral Dexpramipexole Improves Lung Function in ... Dexpramipexole was well tolerated, and had a favorable safety profile. “We are pleased to report positive topline results for the EXHALE-4 phase ...