Dexpramipexole for Asthma

(EXHALE-3 Trial)

Recruiting at 25 trial locations

Overseen By EXHALE Recruiting

Age: Any Age

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Areteia Therapeutics

Must be taking: Inhaled corticosteroids

Must not be taking: Monoclonal antibodies, Pramipexole

Disqualifiers: Severe asthma exacerbation, Respiratory infection, Smoking, others

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: 52

Duration: 52 weeks

930 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of dexpramipexole, a potential treatment for severe eosinophilic asthma that remains poorly controlled. Participants will receive either a high dose, low dose, or a placebo (a pill with no active drug) to assess symptom improvement. It suits individuals who have had asthma for over a year and continue to experience frequent attacks despite regular medication. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking asthma treatment.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current asthma medications. In fact, it requires that you continue using your current asthma controller medications at a stable dose. However, certain medications like pramipexole and specific monoclonal antibody therapies must be stopped before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dexpramipexole is generally well tolerated by people with eosinophilic asthma, a severe type of asthma linked to high levels of a specific white blood cell. Studies indicate that dexpramipexole effectively reduces these cells and is considered safe, as most people did not experience serious side effects.

Earlier research found that dexpramipexole improved lung function without causing major negative effects. Although more studies are needed to confirm these results, current evidence suggests that dexpramipexole is safe for use. ^{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 for treating asthma by potentially reducing eosinophilic inflammation, a key driver of asthma symptoms. Unlike typical asthma medications like inhaled corticosteroids and bronchodilators that primarily open airways or reduce inflammation in a general sense, dexpramipexole may specifically target and lower eosinophil counts, which are often elevated in asthma patients. Researchers are excited because this could mean more effective control of asthma symptoms, especially for those who do not respond well to current treatments.

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

Research has shown that dexpramipexole can lower eosinophils, white blood cells that cause inflammation in asthma. Studies have found that dexpramipexole is safe and helps reduce eosinophils in the blood and airways of people with eosinophilic asthma. This reduction is similar to that achieved with other treatments targeting these cells. Because it can lower eosinophil levels, dexpramipexole is being studied as a promising option for people with severe asthma not well controlled by current treatments. Participants in this trial will receive either dexpramipexole at different dosages or a placebo to further evaluate its effectiveness and safety. ^{1 2 3 4 6}

Who Is on the Research Team?

Michael Wechsler

Principal Investigator

National Jewish Health

Are You a Good Fit for This Trial?

This trial is for adolescents and adults over 12 years old with severe eosinophilic asthma that isn't well-controlled. They should have had at least two asthma attacks in the last year needing steroids, an eosinophil count above a certain level, and not be current smokers or have a heavy smoking history. Women who can get pregnant must use birth control.

Inclusion Criteria

Documented history of at least two asthma exacerbations requiring treatment with systemic corticosteroids within the past 12-month period prior to Screening Visit 1

Male or female ≥12 years of age at randomization

You have evidence of variable airflow obstruction through one or more methodologies.

Exclusion Criteria

You have smoked within the past year or have a history of smoking more than 10 packs of cigarettes.

I have very high blood pressure that isn't controlled by medication.

I have had a severe asthma attack within 4 weeks before my first screening visit up to now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexpramipexole or placebo orally twice a day for 52 weeks

52 weeks

Regular visits throughout the 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexpramipexole Dihydrochloride
• Placebo

Trial Overview The study tests dexpramipexole's safety and effectiveness against a placebo in managing severe eosinophilic asthma. Participants will randomly receive either the actual drug or a placebo to compare outcomes between the two groups.

How Is the Trial Designed?

Group I: 75 mg BID Experimental Treatment 1 Intervention

Dexpramipexole 75 mg oral tablet taken twice a day

Group II: 150 mg BID Experimental Treatment 1 Intervention

Dexpramipexole 150 mg oral tablet taken twice a day

Group III: Placebo Placebo Group 1 Intervention

Placebo 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]

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]

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]

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. 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, ...

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

Safety and Efficacy of Dexpramipexole in Eosinophilic ... 22-25 The current results demonstrating comparable eosinophil lowering as that produced by anti–IL-5 therapies suggest that dexpramipexole may have the ...

6. 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 ...