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

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 history and physical exam * blood and urine tests * lung function tests * electrocardiogram (measures heart electrical activity) * echocardiogram (takes pictures of the heart using sound waves) * bone marrow biopsy (a needle inserted into the hip bone that removes bone marrow cells for study) * After 12 weeks, the participants steroid dose will be tapered again to the lowest effective dose while on study drug. * Two weeks after the lowest effective dose is reached, participants will return for a medical history, physical examination, blood work, lung and heart tests. * Participants who respond to the study drug may be able to continue to receive the drug on a planned separate study. * Four weeks after stopping the study drug, participants will have medical history, physical exam, and blood tests.

Timeline

Start

2014-03-14

Primary completion

2016-12-30

Completion

2019-10-23

Publications

• Background Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, Nutman TB, Pfab F, Ring J, Rothenberg ME, Roufosse F, Sajous MH, Sheikh J, Simon D, Simon HU, Stein ML, Wardlaw A, Weller PF, Klion AD. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009 Dec;124(6):1319-25.e3. doi: 10.1016/j.jaci.2009.09.022.
• Background Bozik ME, Mather JL, Kramer WG, Gribkoff VK, Ingersoll EW. Safety, tolerability, and pharmacokinetics of KNS-760704 (dexpramipexole) in healthy adult subjects. J Clin Pharmacol. 2011 Aug;51(8):1177-85. doi: 10.1177/0091270010379412. Epub 2010 Oct 19.
• Background Cudkowicz ME, van den Berg LH, Shefner JM, Mitsumoto H, Mora JS, Ludolph A, Hardiman O, Bozik ME, Ingersoll EW, Archibald D, Meyers AL, Dong Y, Farwell WR, Kerr DA; EMPOWER investigators. Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial. Lancet Neurol. 2013 Nov;12(11):1059-67. doi: 10.1016/S1474-4422(13)70221-7. Epub 2013 Sep 23.
• Panch SR, Bozik ME, Brown T, Makiya M, Prussin C, Archibald DG, Hebrank GT, Sullivan M, Sun X, Wetzler L, Ware J, Fay MP, Dunbar CE, Dworetzky SI, Khoury P, Maric I, Klion AD. Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes. Blood. 2018 Aug 2;132(5):501-509. doi: 10.1182/blood-2018-02-835330. Epub 2018 May 8.

Drugs

Indications