Dexpramipexole for Asthma

(EXHALE-3 Trial)

Recruiting at25 trial locations

Overseen by Michael Wechsler

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called dexpramipexole to see if it can help people with severe eosinophilic asthma that isn't well-controlled by current treatments. The medication works by lowering the levels of certain cells in the blood that cause inflammation. The goal is to find out if this can improve asthma symptoms and be safe for patients.

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 Dexpramipexole safe for human use?

The research articles provided do not contain specific safety data for Dexpramipexole or its related compounds in humans. ^{1 2 3 4 5}

Research Team

Michael Wechsler

Principal Investigator

National Jewish Health

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Dexpramipexole Dihydrochloride (Other)
• Placebo (Drug)

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.

Participant Groups

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+

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]

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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

Attenuation of nocturnal asthma by cromakalim. [2019]

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

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