Dexpramipexole for Asthma
(EXHALE-2 Trial)
Recruiting in Palo Alto (17 mi)
+261 other locations
Age: 18+
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, COPD, others
Stay on Your Current Meds
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
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.
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.
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.
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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.
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Trial 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 (Other)
Trial OverviewThe 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
3Treatment groups
Experimental Treatment
Placebo Group
Group I: 75 mg BIDExperimental Treatment1 Intervention
Dexpramipexole 75 mg oral tablet taken twice a day
Group II: 150 mg BIDExperimental Treatment1 Intervention
Dexpramipexole 150 mg oral tablet taken twice a day
Group III: PlaceboPlacebo Group1 Intervention
Placebo oral tablet taken twice a day
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research Site US-20001-038Edmond, OK
Research Site 20001-054Hialeah, FL
Research Site US-20001-015Kissimmee, FL
Research Site 20001-374Bakersfield, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Areteia TherapeuticsLead Sponsor
References
RP 49356 and cromakalim relax airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel: a comparison with nifedipine. [2014]RP 49356 is a novel compound which relaxes airway smooth muscle in vitro. Like cromakalim, RP 49356 reduced contractility in guinea pig isolated trachealis under basal conditions or when challenged with low (less than 20 mM) but not high K+. These effects were antagonized by the sulphonylureas glibenclamide and glipizide. This spectrum of action is typical of the class of compounds known as potassium channel openers (KCOs). Unlike RP 49356 and cromakalim, nifedipine had no effect on basal tone, relaxed tissues contracted with low or high K+ and was not antagonized by the sulphonylureas. These data suggest that the KCOs are not acting directly at the voltage-gated Ca++ channel in this tissue. RP 49356 and cromakalim were similar to nifedipine by being more potent at relaxing tissues precontracted with carbachol or histamine (spasmolytic effects) than they were at preventing initiation of the response to these spasmogens (antispasmogenic effects). Because the maintained phase of contraction in airway smooth muscle may be associated with some Ca++ influx, the data presented here suggests that, like nifedipine, the KCOs are more active smooth muscle relaxants under conditions of Ca++ influx. In summary, RP 49356, like cromakalim, is a compound which relaxes airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel which may be similar to the ATP-sensitive K+ channel found in other tissues.
Attenuation of nocturnal asthma by cromakalim. [2019]In a randomised, double-blind, crossover study, single oral doses of cromakalim, a potassium-channel activator, or placebo were given to 23 patients with nocturnal asthma. There was a significant reduction (p less than 0.005) in the early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%). In a repeat dosing study, administration of 0.25 mg and 0.5 mg cromakalim on 5 consecutive nights to a further group of 8 asthmatic subjects significantly reduced the early morning fall in FEV1 from 28.7 (6.5)% after placebo to 19 (4.2)% after 0.25 mg and 14.9 (6.5)% after 0.5 mg. Potassium-channel activators may be useful in the treatment of asthma, especially for nocturnal symptoms.
The action of a potassium channel activator, BRL 38227 (lemakalim), on human airway smooth muscle. [2014]Potassium (K+) channels are present on airway smooth muscle cells, and their activation results in hyperpolarization and relaxation. Because these effects may have therapeutic relevance to asthma, we examined the activity of the active L-enantiomer of cromakalim, BRL 38227 (lemakalim), a selective K+ channel activator, against a variety of spasmogens in human bronchi in vitro. BRL 38227 produced relaxation of bronchi with either resting tone or tone induced by histamine, carbachol, neurokinin A, or KCl (20 mM) with an efficacy (%Emax) of 60 to 80% of that of isoproterenol and an EC50 (the concentration producing 50% of the maximal response) of 0.2 to 0.6 microM. However, BRL 38227 had a significantly lower potency and efficacy against 80 mM KCl than against the other spasmogens (%Emax, 12% of isoproterenol and EC50, 7.2 microM; p less than 0.005 and p less than 0.001, respectively), supporting the view that BRL 38227 acts on K+ channels. The D-enantiomer BRL 38226 was less potent (EC50, 2.6 microM) than BRL 38227 and produced only 43% of the isoproterenol relaxation. BRL 38227-induced relaxation was significantly inhibited by the ATP-sensitive K+ channel antagonist glibenclamide (0.1 and 1 microM), with a three-fold and eight-fold shift to the right of the dose-response curve, respectively. In the presence of a maximal relaxation induced by the calcium voltage-dependent channel antagonist verapamil, BRL 38227 was able to produce an additional 37% relaxation response. Thus, BRL 38227 is an effective relaxant of human airway smooth muscle, and this activity results from an action at K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate. [2019]1. The effects of inhaled nedocromil sodium and sodium cromoglycate on bradykinin-induced bronchoconstriction have been studied in a double-blind, placebo controlled study, in eight mild asthmatic subjects. 2. The subjects attended on four occasions. Fifteen minutes after drug pre-treatment a bradykinin challenge was performed. Increasing concentrations were inhaled until a greater than 40% fall in expiratory flow at 30% of vital capacity from a partial flow volume manoeuvre (V p30) was demonstrated. 3. Inhaled bradykinin (0.06-8.0 mg ml-1) caused dose-related bronchoconstriction with the geometric mean cumulative dose causing a 40% fall in V p30 (PD40) of 0.035 (95% CI: 0.02-0.07) mumol, after placebo inhalation, which was similar to that measured before the trial (0.04: 0.02-0.09 mumol). 4. Both nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) gave significant protection (P less than 0.05) against bradykinin-induced bronchoconstriction (PD40 0.37: 0.19-0.72 mumol after nedocromil sodium and 0.22: 0.11-0.49 after sodium cromoglycate). 5. Since bradykinin-induced bronchoconstriction is probably neurally mediated we conclude that both nedocromil sodium and sodium cromoglycate have an action on neural pathways which may be useful in the control of asthma symptoms.
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]The aim of this study was to assess the bronchodilator effect and short-term safety of cumulative single doses of inhaled bimakalim (E Merck, Darmstadt), a potassium channel opener, compared to placebo in 12 adult patients with chronic, mild to moderate, non-allergic bronchial asthma. The study was a randomized, placebo-controlled, cross-over study and the only efficacy variable measured was the forced expiratory volume in one second (FEV1). The patients had an FEV-1 > 50% of predicted normal value and a reversibility of more than 15% at entrance to the study. Inhaled bimakalim and placebo were delivered by a Pariboy nebulizer. The doses tested in a cumulative manner were 10, 25, 40 and 100 micrograms (total cumulative dose 175 micrograms), each individual dose given at 60-min intervals. Plasma bimakalim concentrations were measured at time 0 and 60 min after each dose. No bronchodilator effect was shown, with inhaled bimakalim at the doses tested. Reasons for the lack of efficacy of inhaled bimakalim in this study may be due to low doses of administered drug or to a true lack of bronchodilatation effect in the study patients. Inhaled bimakalim was well tolerated. No headache or cardiovascular events were seen with the cumulative dose of 175 micrograms bimakalim.