Dexpramipexole for COPD

(SUSPIRE-1 Trial)

Recruiting at37 trial locations

Overseen by Gerard J Criner

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is an open-label Phase II study assessing the PD of dexpramipexole 150 mg twice daily (BID) in participants with eosinophilic COPD. This study will help characterize the profile and duration of reductions of blood absolute eosinophil counts (AEC).

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.

What data supports the effectiveness of the drug Dexpramipexole for COPD?

Dexpramipexole has been shown to reduce eosinophils (a type of white blood cell involved in inflammation) in studies related to nasal polyps, which might suggest potential anti-inflammatory benefits for COPD, a condition often involving inflammation. ^{1 2 3 4 5}

How does the drug Dexpramipexole differ from other treatments for COPD?

Dexpramipexole is unique because it has been shown to reduce eosinophils (a type of white blood cell involved in inflammation) in blood and tissues, which may help in conditions like COPD where inflammation is a key issue. This mechanism is different from many standard COPD treatments that primarily focus on bronchodilation (widening of the airways) and reducing symptoms. ^{1 3 4 6 7}

Research Team

Gerard J Criner

Principal Investigator

Temple University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Dexpramipexole (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The behavioural effects of pramipexole, a novel dopamine receptor agonist. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

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

5. New Zealand pubmed.ncbi.nlm.nih.gov

Pramipexole extended release: in Parkinson's disease. [2018]

6. England 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. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. [2019]