Clinical Trial: Study to Evaluate Safety and Efficacy of Dexpramipexole (KNS-760704) in Subjects With Hypereosinophilic Syndrome

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: An Open-Label, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Dexpramipexole (KNS-760704) in Subjects With Hypereosinophilic Syndrome

Brief Summary:

Background:

- Eosinophils are white blood cells that fight infections. In people with hypereosinophilic syndrome (HES), eosinophil levels are too high and can damage their organs. HES is usually treated with steroids, but steroids can cause side effects and stop working over time. Researchers want to see if a drug called dexpramipexole, being developed by Knopp Pharmaceuticals, can help people with HES to reduce their steroid dose.

Objective:

- To test whether dexpramipexole can reduce the steroid dose needed to control eosinophilia and HES symptoms.

Eligibility:

- Adults 18 and older with HES who respond to steroids, but need more than 10 mg daily to control eosinophilia and symptoms.

Design:

  • The study will last 9 months with 6 visits to NIH.
  • Participants will be screened with medical history, physical exam, and urine and blood samples.
  • Participants steroids will be tapered to the lowest effective dose. During this time, blood will be drawn weekly. Participants will take this dose for 2 weeks before starting the study drug.
  • Participants will take the study drug twice daily by mouth for 12 weeks along with steroids. The steroid dose will not be decreased during this time and participants will be seen monthly for a medical history, physical examination and blood work.
  • Just before and 12 weeks after starting the study drug, the following tests will be performed:
  • medical histor

    Detailed Summary:

    Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders characterized by peripheral eosinophilia and evidence of eosinophil-related end organ damage. Although a high proportion of patients respond initially to corticosteroid therapy, high doses are often necessary to control the eosinophilia and clinical symptoms, and many patients become relatively refractory to therapy and/or develop serious side effects.

    Dexpramipexole (KNS 760704) is a synthetic aminobenzothiazole shown to safely reduce blood eosinophils counts in individuals with amyotrophic lateral sclerosis (ALS) in several clinical trials. The purpose of this proof-of- concept study is to evaluate the effect of dexpramipexole, an orally bioavailable small molecule, on circulating and tissue eosinophils in 10 subjects with HES. Following completion of eligibility assessments, subjects with absolute eosinophil count (AEC) < 1000/uL will enter a lead-in period, during which a standardized weekly corticosteroid taper will be undertaken to establish a "minimally effective corticosteroid dose" in each study subject. For subjects whose symptoms are stable but AEC > 1000/uL at the time of enrollment, the steroid dose at the time of enrollment will be defined as the minimally effective corticosteroid dose and no taper will be performed. Once the minimally effective corticosteroid dose is established, treatment with dexpramipexole 150 mg twice daily will begin. A standardized corticosteroid taper will begin after 12 weeks of treatment with dexpramipexole to determine the "minimally effective corticosteroid dose on dexpramipexole". Eosinophil counts and routine chemistries will be monitored weekly during corticosteroid tapering. End organ assessment, including echocardiogram, pulmonary function testing, and other studies as appropriate will be performed at study baseline, initiation
    Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

    Current Primary Outcome:

    • The corticosteroid dose after treatment with 150 mg twice daily of dexpramipexole as a percentage of the corticosteroid dose prior to treatment [ Time Frame: After 3 months of taking dexpramipexole ]
    • The number of subjects with a greater than or equal to 50 % change in prednisone (or equivalent) dose to maintain absolute eosinophil count (AEC) at or below baseline (pre-enrollment)levels and control clinical symptoms [ Time Frame: After 3 months of taking dexpramipexole ]


    Original Primary Outcome: A binary response indicating whether or not the subject had a greater than or equal to 50 % change in prednisone dose to maintain AEC & lt; 1000/microL and control clinical symptoms and 2) the change in minimal effective corticosteroid dose... [ Time Frame: 3-6 months ]

    Current Secondary Outcome:

    • Reduction in circulating eosinophil and bone marrow eosinophil count after 3 months of treatment with dexpramipexole (prior to steroid taper) [ Time Frame: After 3 months of dexpramipexole therapy ]
    • The number of subjects able to taper to <10 mg prednisone (or equivalent) dose to maintain absolute eosinophil count (AEC) at or below baseline (pre-enrollment) levels and control clinical symptoms [ Time Frame: After 3 months of dexpramipexole therapy ]
    • Incidence and severity of adverse events [ Time Frame: During dexpramipexole therapy ]


    Original Secondary Outcome:

    • Reduction in circulating eosinophils after 3 months of treatment with dexpramipexole (prior to steroid taper) [ Time Frame: 3 months ]
    • Reduction in bone marrow eosinophils and myeloid precursors after 3 months of treatment with dexpramipexole (prior to steroid taper) [ Time Frame: 3 months ]
    • Number of subjects able to taper to & lt; 10 mg prednisone and maintain AEC& lt; 1000/microL and control of clinical symptoms [ Time Frame: 9 months ]
    • Incidence and severity of adverse events [ Time Frame: 9 months ]


    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: March 14, 2014
    Date Started: February 20, 2014
    Date Completion: February 28, 2018
    Last Updated: May 12, 2017
    Last Verified: December 21, 2016