Dexpramipexole for Asthma

(EXHALE-2 Trial)

Not currently recruiting at 450 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new asthma treatment called dexpramipexole. The goal is to determine if this medication can help individuals with asthma that remains difficult to control despite using other asthma medications. The trial compares dexpramipexole to a placebo (a pill with no active medicine) to assess its effectiveness and safety. Suitable candidates for this trial include those who have had asthma for at least a year, experience frequent asthma attacks, and currently use daily asthma medications that do not fully control their symptoms. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking asthma therapy.

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

Research shows that dexpramipexole is usually well-tolerated by people with eosinophilic asthma. Studies have found that it effectively reduces eosinophil levels, a type of white blood cell associated with asthma. Importantly, these studies report that participants experienced few side effects. Most people taking dexpramipexole did not encounter serious negative effects, suggesting it is safe to use. However, more large-scale studies are needed to fully understand its safety. ^{1 2 3 4 5}

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

Dexpramipexole is unique because it targets asthma in a new way compared to standard treatments like inhaled corticosteroids, beta-agonists, and leukotriene modifiers. Unlike these options, which primarily focus on reducing inflammation and relaxing airway muscles, dexpramipexole works by potentially altering eosinophil levels, a type of white blood cell involved in asthma. Researchers are excited about this treatment because it offers a novel approach to managing asthma, which could lead to more effective control of symptoms for certain patients who don't respond well to existing medications. Additionally, the availability of different dosing options—75 mg and 150 mg taken orally twice a day—provides flexibility in tailoring the treatment to individual patient needs.

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

Research shows that dexpramipexole may help treat asthma, particularly in individuals with a type linked to high levels of eosinophils, a specific white blood cell. Earlier studies demonstrated that dexpramipexole successfully reduced eosinophil levels. Eosinophils are associated with asthma symptoms and flare-ups. The treatment was well tolerated by patients, causing few side effects. This trial will evaluate different dosages of dexpramipexole, with some participants receiving 75 mg and others 150 mg, to confirm its effectiveness in reducing asthma attacks in those with high eosinophil levels. Early results appear promising. ^{1 2 3 6 7}

Who Is on the Research Team?

Salman Siddiqui, MD

Principal Investigator

Imperial College Healthcare NHS Trust (via Imperial Consultants)

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

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

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]

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]

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 ...