Ignite Creation Date:
2024-05-06 @ 2:50 AM
Last Modification Date:
2024-10-26 @ 11:23 AM
Study NCT ID:
NCT02130882
Status:
UNKNOWN
Last Update Posted:
2022-02-08
First Post:
2014-04-03
Brief Title:
Study to Evaluate Safety and Efficacy of Benralizumab in Subjects With Hypereosinophilic Syndrome
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase 2a Randomized Double-Blind Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutaneous Benralizumab MEDI-563 in Reducing Eosinophilia in Subjects With Hypereosinophilic Syndrome HES
Status:
UNKNOWN
Status Verified Date:
2021-09-09
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HESIL5R
Brief Summary:
Background
- Eosinophils are white blood cells that help fight infections High eosinophil levels can damage people s organs causing hypereosinophilic syndrome HES Researchers want to study if the drug benralizumab can help people with HES
Objective
- To test if benralizumab can safely decrease eosinophils in people with HES
Eligibility
- Adults age 18-65 who have been on stable HES therapy for at least 1 month but still have symptoms and high eosinophil levels
Design
Participants will be screened with medical history physical exam and urine and blood tests They will take simple heart and lung tests
Participants will also have a bone marrow biopsy A numbing medicine is injected into the outer covering of the bone Then a needle is inserted into the bone A fast suction movement takes bone marrow cells
Phase 1 Participants will randomly receive either the study drug or placebo as an injection
They will have daily visits for the next 3 days then 4 weekly visits and then 4 biweekly visits Each time they will have medical history physical exam blood tests and a check of side effects
They will receive another dose of the study drug or placebo at 1 month and 2 months after the first injection
Phase 2 repeats the Phase 1 schedule All participants will receive the study drug
At 1 visit participants will also receive a vaccine At 4 visits they will repeat the heart and lung tests They will also have one other bone marrow biopsy
After week 24 participants will receive the study drug either 6 times over 6 months or twice over 6 months
- Eosinophils are white blood cells that help fight infections High eosinophil levels can damage people s organs causing hypereosinophilic syndrome HES Researchers want to study if the drug benralizumab can help people with HES
Objective
- To test if benralizumab can safely decrease eosinophils in people with HES
Eligibility
- Adults age 18-65 who have been on stable HES therapy for at least 1 month but still have symptoms and high eosinophil levels
Design
Participants will be screened with medical history physical exam and urine and blood tests They will take simple heart and lung tests
Participants will also have a bone marrow biopsy A numbing medicine is injected into the outer covering of the bone Then a needle is inserted into the bone A fast suction movement takes bone marrow cells
Phase 1 Participants will randomly receive either the study drug or placebo as an injection
They will have daily visits for the next 3 days then 4 weekly visits and then 4 biweekly visits Each time they will have medical history physical exam blood tests and a check of side effects
They will receive another dose of the study drug or placebo at 1 month and 2 months after the first injection
Phase 2 repeats the Phase 1 schedule All participants will receive the study drug
At 1 visit participants will also receive a vaccine At 4 visits they will repeat the heart and lung tests They will also have one other bone marrow biopsy
After week 24 participants will receive the study drug either 6 times over 6 months or twice over 6 months
Detailed Description:
Hypereosinophilic syndrome HES is a rare group of heterogeneous disorders characterized by marked peripheral eosinophilia 1500microL and evidence of eosinophil-associated tissue 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 andor develop serious side effects IL-5 receptor alpha expression in humans is restricted to eosinophils basophils mast cells and their precursors and is therefore an ideal target for the therapy of HES To date there have been no safety concerns with benralizumab anti-IL-5 receptor alpha in phase 1 2 and 3 trials in asthma and efficacy data is promising In order to explore the safety and efficacy of benralizumab in the treatment of HES 20 adults men and non-pregnant women 18-75 years of age with HES who are symptomatic with absolute eosinophil count 1000microL on stable HES therapy for at least 1 month will be recruited for this randomized placebo-controlled double-blind phase 2 trial Benralizumab 30 mg or placebo will be administered sc at weeks 0 4 and 8 Eosinophil counts will be blinded for a subject and background HES therapy will not be tapered until that subject has been on study for 13 weeks At weeks 12 16 and 20 all subjects will receive a sc injection of benralizumab Subjects demonstrating a response at the 24 week visit eosinophil count 1000alpha L and stable or improved clinical symptoms without an increase in background HES therapy will continue to receive additional 30 mg sc injections every 4 weeks Following the initial dose of benralizumab or placebo and the first open-label dose of benralizumab subjects will be followed daily for 3 days weekly for 4 weeks and every 2 weeks for 8 weeks Subsequent visits will be at 4 weeks intervals for responders and 12 weeks intervals for non-responders for a minimum of two years Subjects with stable and complete response for greater than or equal to 2 years may be eligible to receive benralizumab at a dosing interval of every 8 weeks Subjects will receive diphtheria-tetanus-acellular pertussis TdaP booster immunization at the 22 week visit Titers will be measured 6 weeks after immunizationThe primary endpoint of the study is a 50 reduction in peripheral blood eosinophilia on stable background therapy at 12 weeks post-initiation of study drug Secondary endpoints will include absolute eosinophil count the frequency and severity of adverse events reduction in signs and symptoms of HES tissue eosinophilia numbers of eosinophils mast cells and their precursors in bone marrow levels of markers of eosinophil and mast cell activation eosinophil count and background HES therapy at 1 year pharmacokinetics and anti-drug antibody ADA levels and eosinophil count after 24 weeks of every 8 week dosing Exploratory endpoints will address predictors of response to benralizumab and the impact of eosinophil depletion on vaccine responses and glucose homeostasis Subjects who complete the study and for whom benralizumab provides sustained clinical benefit may be eligible to receive drug on an open-label extension protocol until regulatory approval and commercial availability of the marketed drug to prescribing physicians for any indication or until development of benralizumab is discontinued by MedImmune
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None