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

NCT02101138 | Unknown Phase 2

• 2 other identifiers: 14006314-I-0063
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Hypereosinophilic Syndrome

Keywords

Corticosteroids; Eosinophilia

Outcome Measures

Primary Outcomes (2)

• The corticosteroid dose after treatment with 150 mg twice daily of dexpramipexole as a percentage of the corticosteroid dose prior to treatment

  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

  After 3 months of taking dexpramipexole

Secondary Outcomes (3)

• Reduction in circulating eosinophil and bone marrow eosinophil count after 3 months of treatment with dexpramipexole (prior to steroid taper)

  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

  After 3 months of dexpramipexole therapy

• Incidence and severity of adverse events

  During dexpramipexole therapy

Study Arms (1)

Dexpramipexole

EXPERIMENTAL

Dexpramipexole treatment

Drug: Dexpramipexole

Interventions

Dexpramipexole DRUG

Dexpramipexole (KNS 760704) is a synthetic amino-benzothiazole developed for use in amyotrophic lateral sclerosis (ALS)

Dexpramipexole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject will be eligible for participation in the study only if all of the following criteria apply:
• The subject is male or female, age greater than or equal to 18 years
• The subject has a documented history of HES requiring greater than or equal to 10 mg prednisone (or equivalent) to maintain disease control.
• HES symptoms are stable on the current corticosteroid dose.
• The subject agrees to storage of samples for study.
• Females are eligible for this study if they are:
• (1) of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal as defined by no menses in 1 year); OR
• (2) of childbearing potential but willing to practice effective contraception or abstinence during administration of the study drug and for 3 months after administration of the investigational study drug (dexpramipexole).
• Participation of Women:
• Contraception: Pre-clinical animal data demonstrated some fetal risk, suggesting there may a human reproductive risk. Subjects must agree not to become pregnant. Females of childbearing potential must have a pregnancy test before the first dose of dexpramipexole. Because of the risk involved, subjects and their partners must use two methods of birth control. They must continue to use both methods for 3 months after stopping the study drug. Two methods of birth control may be selected from the list included below:
• Hormonal contraception
• Male or female condoms with or without a spermicide
• Diaphragm or cervical cap with a spermicide
• Intrauterine device (IUD)
• If pregnancy is suspected or should occur, subjects must notify the study staff immediately.

You may not qualify if:

• A subject will not be eligible to participate in the study if any of the following conditions are fulfilled at the time of enrollment:
• Life-threatening HES or other condition that, in the Investigator s opinion, places the subject at undue risk by participating in the study
• Pregnant or breast-feeding
• 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)
• HIV infection or any other known immunodeficiency.
• Biopsy-proven eosinophilic granulomatosis with polyangiitis
• Positive test for FIP1L1/PDGFRA fusion gene
• Absolute neutrophil count \<2000/microL at screening, or any documented history of neutropenia
• Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) of less than or equal to 80 mg/dL at screening (estimation of creatinine clearance using the MDRD formula).
• Cardiac abnormality defined as:
• Moderate to severely decreased cardiac function (left ventricular ejection fraction (LVEF) \< 20% or history of LVEF \<20% within the past 6 months or NYHA class IIIb or IV)
• History of angina or acute myocardial infarction in the past 6 months
• History or long QT syndrome or arrhythmia.
• A prolongation of QT/QTc interval (e.g., repeated demonstration of a QT/QTc interval \>450 ms before study treatment administration) at screening, admission or pre-dose on Day 1.
• Any clinically important abnormalities in resting ECG that may interfere with the interpretation of QTc interval changes at screening, admission or pre-dose on Day 1.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Knopp Biosciences: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 19910029 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.

  PMID: 20959524 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.

  PMID: 24067398 BACKGROUND

• 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.

  PMID: 29739754 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hypereosinophilic Syndrome; Eosinophilia

Interventions

Dexpramipexole

Condition Hierarchy (Ancestors)

Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Amy D Klion, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2014
• First Posted: April 2, 2014
• Study Start: March 14, 2014
• Primary Completion: December 30, 2016
• Study Completion: October 23, 2019
• Last Updated: December 7, 2017

Record last verified: 2017-12-01

Locations

US (1)