Study of Dexpramipexole Chronic Sinusitis With Nasal Polyps and Eosinophilia

Study Overview
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Brief Summary
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Phase 2, open-label, multi-center study to evaluate the clinical effects of oral administration of dexpramipexole for 6 months in subjects with chronic sinusitis with nasal polyps and eosinophilia.

Detailed Description
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This open-labelled study will evaluate the safety and preliminary efficacy of dexpramipexole for reducing the number of eosinophils in the peripheral blood and in improving nasal polyp score when administered to 20 subjects with chronic sinusitis with nasal polyps and eosinophilia. Subjects will received dexpramipexole for up to 6 months and will have safety tests performed monthly and will have efficacy evaluations performed at month 1, month 3, and month 6 after beginning study drug.

Official Title
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Safety and Preliminary Efficacy of Dexpramipexole in Patients With Chronic Sinusitis With Nasal Polyps and Eosinophilia (CSNP-E)

Conditions
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Chronic Sinusitis With Nasal Polyps and Eosinophilia

Intervention / Treatment
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* Drug: dexpramipexole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female >18 or <70 years of age Willing to practice effective contraception during the study and be willing and able to continue contraception for 1 month (females) or 3 months (males) after the last dose of study treatment Confirmed diagnosis of chronic sinusitis with nasal polyps Documented history of nasal eosinophilia Documented peripheral absolute eosinophil count >300 cells/μL Bilateral total polyp score of >4 Sino-nasal outcome test (SNOT-22) score of >7 Using an intranasal corticosteroid spray or irrigation (< 1000 μg/day beclomethasone or equivalent) Exclusion Criteria: Acute sinusitis, concurrent nasal infection, or subjects who have had a nasal or upper respiratory tract infection within 2 weeks prior to baseline CT scan suggestive of allergic fungal rhinosinusitis Nasal septal deviation that would occlude at least one nostril Nasal surgery (including polypectomy) within 6 months prior to baseline History of more than 5 sinonasal surgeries requiring general anesthesia History of more than 2 sinonasal surgeries that changed the lateral wall of the nose History of cystic fibrosis, primary ciliary's dysfunction or Kartagener's syndrome History of diagnosis with a parasitic infection Hospitalization or emergency treatment for the treatment of asthma two or more times in the 12 months prior to baseline Hospitalization for an acute asthmatic attack within 4 weeks prior to baseline Forced expiratory volume (FEV1) of <60% of predicted normal range Treatment with a systemic corticosteroid or intra-polyp corticosteroid within 8 weeks prior to baseline or anticipated need for systemic corticosteroids during the study treatment period Utilization of rescue oral corticosteroids for asthma or chronic sinusitis exacerbation more than one time within the past 1 year Treatment with an investigational drug in the previous 30 days or 5-half-lives, whichever is longer Treatment with a monoclonal antibody therapy including omalizumab (Xolair®), within 5-half-lives Treatment with zileuton (Zyflo®) within 4 weeks of baseline Treatment with pramipexole (Mirapex®) within 4 weeks of baseline History of malignancy, including solid tumors and hematologic malignancies (except basal cell and squamous cell cancers of the skin that have been completely excised and cured) History of human immunodeficiency virus (HIV) or hepatitis B or C History of unstable or severe cardiac, hepatic, or renal disease, or other medically significant illness Medical or other condition likely to interfere with subject's ability to undergo study procedures, adhere to visit schedule or comply with study requirements Absolute neutrophil count <2000 cells/μL at screening, or any documented history of neutropenia Total IgE >1500 IU/ml at any visit prior to baseline Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) of ≤80 mg/dL at screening (estimation of creatinine clearance using the MDRD formula) History of long QT syndrome or arrhythmia Prolongation of QT/QTc interval (e.g., repeated demonstration of a QT/QTc interval >450 ms) at screening or pre-dose on day 1 Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTc interval changes at screening or pre-dose on day 1, including any of the following: PR interval >210 ms; QRS >110 ms; Heart rate <45 bpm or >100 bpm (average of 3 assessments). Pregnant women or women breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dexpramipexole<br>dexpramipexole 150 mg BID | Drug: dexpramipexole<br>* Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)<br>* Other names: RPPX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio to Baseline in Peripheral Blood Eosinophil Counts After 6 Months of Treatment | Change in peripheral blood eosinophil (measured in cells/μL) from baseline to month 6 is presented as ratio to baseline. | Baseline and Month 6 | 
| Change From Baseline in Total Polyp Score (TPS) After 6 Months of Treatment | The change in Nasal Polyp Score (NPS) score after 6 months of treatment is presented. A blinded Central Endoscopy Rater determined the NPS for each nare on a scale of 0 to 4, and the bilateral NPS scores were added to generate the Total Polyp Score (TPS) on a scale of 0 to 8. A lower TPS corresponds to a lower polyp burden. | Baseline and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Potentially Clinically Significant Values in Clinical Laboratory Evaluations | Summary of subjects from the safety population who experienced potentially clinically significant values in hand serum chemistry results | 6 months | 
| Number of Subjects With Potentially Clinically Significant Values in Vital Signs and Weight | Summary of subjects from the safety population who experienced potentially clinically significant values or changes in vital signs or weight | 6 months | 
| Number of Subjects With Potentially Significant Values in Electrocardiogram Parameters | Summary of subjects from the safety population who experienced potentially significant values in electrocardiogram parameters | 6 months | 
| Ratio to Baseline in Peripheral Blood Eosinophil Counts After 3 Months of Treatment | Change in peripheral blood eosinophil (measured in cells/μL) from baseline to month 3 is presented as ratio to baseline. | Baseline and Month 3 | 
| Change From Baseline in TPS After 3 Months of Treatment | The change in Nasal Polyp Score (NPS) score after 3 months of treatment is presented. A blinded Central Endoscopy Rater determined the NPS for each nare on a scale of 0 to 4, and the bilateral NPS scores were added to generate the Total Polyp Score (TPS) on a scale of 0 to 8. A lower TPS corresponds to a lower polyp burden. | Baseline and Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sinusitis, Rhinosinusitis, CRS, CRSwNP, CSNP-E, Nasal polyps, Nasal polyposis, Eosinophilia, Asthma