Study of Dexpramipexole Chronic Sinusitis With Nasal Polyps and Eosinophilia
Condition: Chronic Sinusitis With Nasal Polyps and Eosinophilia
MeSH terms: Sinusitis; Nasal Polyps; Eosinophilia; Polyps; Chronic Disease
Intervention: dexpramipexole
Intervention description: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Intervention MeSH terms: Pramipexole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Sinusitis; Rhinosinusitis; CRS; CRSwNP; CSNP-E; Nasal polyps; Nasal polyposis; Eosinophilia; Asthma

Summary:

      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.
    

Eligibility criteria:

        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