Dexpramipexole for COPD

(SUSPIRE-1 Trial)

Not currently recruiting at 39 trial locations

Overseen By SUSPIRE-1 Recruiting

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Areteia Therapeutics

Must be taking: ICS-based therapy

Must not be taking: Monoclonal antibodies, Pramipexole

Disqualifiers: Asthma, Pulmonary disease, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of dexpramipexole, an experimental treatment, for individuals with eosinophilic COPD. This type of chronic lung disease is marked by high levels of eosinophils, a type of white blood cell, in the blood. Researchers aim to determine if this treatment can reduce these blood cells and help manage COPD symptoms. Ideal candidates for this trial have had COPD for at least two years and a history of smoking. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you have been on a stable dose of your COPD medication for at least 4 weeks before joining. Some specific medications, like certain monoclonal antibodies and pramipexole, must not have been used recently.

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

Research has shown that dexpramipexole has been tested in people with severe asthma. These studies found that dexpramipexole is generally well-tolerated. It reduced eosinophils, white blood cells linked to inflammation, without causing major side effects. Although more research is needed to fully understand its safety, current evidence suggests that dexpramipexole is safe for humans in these studies. ^{1 2 3 4 5}

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

Most treatments for COPD, like bronchodilators and corticosteroids, aim to open airways or reduce inflammation. But dexpramipexole works differently, targeting eosinophils, which are cells involved in inflammation. Researchers are excited about dexpramipexole because it offers a new way to manage COPD by potentially reducing inflammation at its source, rather than just treating symptoms. This unique approach could lead to better long-term outcomes for patients.

What evidence suggests that dexpramipexole might be an effective treatment for COPD?

Research has shown that dexpramipexole, the investigational treatment in this trial, may help lower the number of eosinophils in the blood. Eosinophils, a type of white blood cell, can cause inflammation and worsen conditions like COPD (chronic obstructive pulmonary disease). Studies have found that dexpramipexole can greatly improve lung function. Other research indicates that dexpramipexole effectively reduces eosinophils and is well tolerated by participants. These early findings suggest it could benefit people with eosinophilic COPD. ^{1 2 3 5 6}

Who Is on the Research Team?

Gerard J Criner

Principal Investigator

Temple University

Are You a Good Fit for This Trial?

This trial is for adults aged 40-80 with eosinophilic COPD, a history of smoking, and recent exacerbations. They must have been on stable ICS-based therapy for at least 12 weeks. Exclusions include significant heart or liver disease, certain infections, other lung diseases besides COPD, recent use of drugs affecting blood cells or QT interval, pregnancy/breastfeeding women, and those not using birth control.

Inclusion Criteria

Signed informed consent form prior to any study-specific procedures

I am between 40 and 80 years old.

Evidence of an eosinophilic phenotype with blood eosinophils at least 0.30x10^9/L at the Screening Visit

Exclusion Criteria

I haven't taken drugs with a high risk of neutropenia or QT prolongation in the last 30 days.

I have had severe heart failure or a weak heart pump.

My liver isn't working properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexpramipexole 150 mg twice daily to assess pharmacodynamic effects

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexpramipexole

Trial Overview The study tests the effects of Dexpramipexole Dihydrochloride (150 mg twice daily) on people with eosinophilic COPD to see how it affects their blood eosinophil counts. It's an open-label Phase II trial where all participants know they're receiving the medication.

How Is the Trial Designed?

Group I: 150 mg dexpramipexole BID Experimental Treatment 1 Intervention

150 mg dexpramipexole 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 6-month study involving 16 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilia, the investigational drug dexpramipexole significantly reduced blood eosinophil counts by 94%, indicating its strong eosinophil-lowering activity.

Despite the substantial reduction in eosinophils in both blood and nasal polyp tissue, there was no significant improvement in nasal polyp scores or other clinical symptoms, suggesting that eosinophil reduction alone may not translate to clinical efficacy in CRSwNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size. Laidlaw, TM., Prussin, C., Panettieri, RA., et al.[2019]

Pramipexole, a dopamine agonist, shows potential antidepressant properties as it influences locomotion and operant behavior in female NMRI mice, suggesting it may help alleviate depressive symptoms.

The study found that low doses of pramipexole increased operant behavior in mice with 'low temporal control,' indicating a possible mechanism for its anti-anhedonic effects, which could be beneficial in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice. Lehr, E.[2019]

Pramipexole extended release (ER) is effective in improving Parkinson's disease symptoms, showing significant reductions in the Unified Parkinson's Disease Rating Scale (UPDRS) scores compared to placebo in trials involving patients with early and advanced disease.

The once-daily pramipexole ER formulation leads to fewer fluctuations in drug levels compared to the immediate release version, and it was generally well tolerated, with adverse event rates similar to those of pramipexole immediate release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramipexole extended release: in Parkinson's disease. Chwieduk, CM., Curran, MP.[2018]

Pramipexole acts as a dopamine D2 receptor agonist, showing different effects based on dosage: low doses (0.001-0.1 mg/kg) induce locomotor hypoactivity, while higher doses (0.3-1 mg/kg) lead to hyperactivity, indicating its complex role in modulating dopamine activity.

The study suggests that pramipexole may have potential antipsychotic effects at low doses and antiparkinsonian effects at higher doses, as it can counteract akinesia and enhance the effects of L-DOPA in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The behavioural effects of pramipexole, a novel dopamine receptor agonist. Maj, J., Rogóz, Z., Skuza, G., et al.[2019]

A physiologically based pharmacokinetic (PBPK) model for pramipexole was developed and validated, showing that renal function significantly affects the drug's clearance, particularly through the organic cation transporter 2 (OCT2).

In patients with varying degrees of renal impairment, the model predicts that pramipexole dosing should be adjusted, with no change needed for mild impairment, but reductions required for moderate (0.125 mg twice daily), severe (0.125 mg once daily), and end-stage renal disease (0.0375 mg once daily) to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a Physiologically Based Pharmacokinetic Model for Prediction of Pramipexole Pharmacokinetics in Parkinson's Disease Patients With Renal Impairment. You, X., Wu, W., Xu, J., et al.[2021]

Pramipexole shows a strong preference for binding to dopamine D3 receptors, being five times more selective for them compared to D2 and D4 receptors, based on binding affinity studies with both rat and human receptors.

The drug's potency in activating D3 receptors may contribute to its effectiveness as a dopamine autoreceptor agonist, which helps explain its therapeutic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Mierau, J., Schneider, FJ., Ensinger, HA., et al.[2019]

Both the S(-) and R(+) enantiomers of pramipexole are effective in preventing cell death and reducing mitochondrial reactive oxygen species (ROS) generation in neuroblastoma cells, indicating their potential as neuroprotective agents.

The neuroprotective effects of pramipexole enantiomers are independent of their ability to stimulate dopamine receptors, suggesting that both forms may serve as mitochondria-targeted antioxidants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole. Ferrari-Toninelli, G., Maccarinelli, G., Uberti, D., et al.[2021]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06533553

NCT06533553 | A Study to Assess the Effects of ... This is an open-label Phase II study assessing the PD of dexpramipexole 150 mg twice daily (BID) in participants with eosinophilic COPD.

3. firstwordpharma.com firstwordpharma.com/story/6092869

Areteia Therapeutics Announces Positive Topline Results ... In the EXHALE-4 study, dexpramipexole met the primary endpoint with statistically significant improvement in lung function compared with ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37277072/

Safety and Efficacy of Dexpramipexole in Eosinophilic ... Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand the clinical ...

5. trials.foodallergy.org trials.foodallergy.org/trials/NCT05763121

A Study to Assess the Effect of Dexpramipexole in Adolescents and ... This study will assess the efficacy and safety of dexpramipexole as an adjunctive oral therapy in participants with inadequately controlled asthma with an ...

6. researchgate.net researchgate.net/publication/371285354_Safety_and_efficacy_of_dexpramipexole_in_eosinophilic_asthma_EXHALE_a_randomized_controlled_trial

Safety and Efficacy of Dexpramipexole in Eosinophilic ... In patients with moderate to severe asthma, dexpramipexole significantly reduced blood eosinophils and nasal eosinophil peroxidase (a biomarker ...