Dexpramipexole for Asthma

(EXHALE-2 Trial)

Recruiting at 318 trial locations

Overseen By EXHALE Recruiting

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Areteia Therapeutics

Must be taking: Inhaled corticosteroids

Must not be taking: Monoclonal antibodies, Pramipexole

Disqualifiers: Severe asthma exacerbation, COPD, others

Stay on Your Current Meds You can continue your current medications while participating

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: 36

Duration: 52 weeks

1395 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not require you to stop your current asthma medications, as long as they are stable and have been used for at least 3 months before the screening. However, certain medications like pramipexole and specific monoclonal antibody therapies must be stopped before joining.

Is Dexpramipexole generally safe for humans?

The research on potassium channel openers, like bimakalim, shows that they were well tolerated in studies with asthma patients, with no significant side effects such as headaches or cardiovascular issues reported at the doses tested. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing an oral medication called dexpramipexole in people with severe asthma that isn't well controlled by usual treatments. The medication aims to reduce certain cells in the blood that make asthma worse, helping to better manage symptoms.

Research Team

Salman Siddiqui, MD

Principal Investigator

Imperial College Healthcare NHS Trust (via Imperial Consultants)

Eligibility Criteria

This trial is for adolescents and adults aged 12 or older with severe eosinophilic asthma that isn't well-controlled, despite current treatments. Participants must have had at least two asthma attacks in the past year requiring steroids. Women who can have children must use effective birth control.

Inclusion Criteria

I've needed steroids for asthma attacks at least twice in the last year.

Women not of childbearing potential must meet specific criteria

I have been diagnosed with asthma for at least a year.

Exclusion Criteria

General medical history criteria including weight, smoking, alcohol or drug abuse, uncontrolled severe hypertension, history of malignancy, HIV infection, helminth parasitic infection, medical or other condition likely to interfere with participant's ability to undergo study procedures, adhere to visit schedule, or comply with study requirements, known or suspected noncompliance with medication, unwillingness or inability to follow the procedures outlined in the protocol

I have not taken any medications or undergone procedures that are not allowed in this trial.

My white blood cell count is low.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexpramipexole or placebo orally for 52 weeks

52 weeks

Visits at baseline, Weeks 36, 44, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexpramipexole Dihydrochloride

Trial Overview The study tests Dexpramipexole as an additional oral treatment against a placebo to see if it helps people with a specific type of severe asthma. The goal is to find out if this new medicine can reduce asthma symptoms and prevent attacks.

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]

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]

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

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

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

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

5. 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]