Clinical trial NCT04538989: An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
Official title: An Open-Label Multiple-Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congenital Hyperinsulinism
Keywords: Hypoglycemia
Congenital Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Hyperinsulinism
Lead sponsor: Rezolute
Sponsor class: OTHER
First posted: 2020-09-04
Enrollment: 23
Sex: ALL
Minimum age (years): 2
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The objective of this trial is to evaluate the safety, tolerability and glucose-raising effects of RZ358 in patients with Congenital Hyperinsulinism (HI).

Detailed description: There is a significant unmet medical need to develop new therapies aimed at preventing chronic recurrent hypoglycemia in congenital HI, the most common cause of persistent hypoglycemia in children. RZ358 is a human mAb that allosterically attenuates excessive insulin action on target cells. Therefore, RZ358 is ideally suited as a potential therapy for hyperinsulinism, and it is being developed to treat the hypoglycemia associated with diseases such as congenital HI. This is a Phase 2, multicenter, open label clinical study designed to assess the safety and efficacy of four progressively higher doses of RZ358 in separate groups of patients with hyperinsulinemic hypoglycemia due to Congenital HI, not adequately controlled with or without current standard of care. A screening period of up to 5 weeks will evaluate eligibility. Once enrolled, RZ358 will be administered bi-weekly over 8 weeks, and then patients will complete a post-treatment follow-up period of 13 weeks.

Eligibility criteria: Inclusion Criteria:

* Male or female age 2-45 years old (except age 12-45 in US) with an established clinical diagnosis of congenital hyperinsulinism
* Able to provide written informed consent or, as applicable, assent
* Confirmed hypoglycemia as assessed by CGM, SMBG, and clinical evaluation, during Screening
* Willingness to use contraception if of child-bearing potential

Exclusion Criteria:

* Out of range blood work for study entry
* Body Mass index outside of study entry criteria
* History of malignancy
* Clinically significant diseases, seropositivity for HIV, hepatitis B or C antibody
* Use of systemic corticosteroids within 30 days before Screening
* Known or suspected allergy to the study drug
* Recent use of an investigational drug or treatment, or participation in an investigational study
* Pregnant or lactating women
* History of drug abuse or excessive alcohol use

Primary outcomes:
measure: Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)
timeFrame: 8 weeks
measure: Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)
timeFrame: 8 weeks
measure: Repeat Dose Pharmacokinetics of RZ358
timeFrame: Pre dose Weeks 1,3,5,7, 1-hr post dose Week 1 and Week 7, and Follow up on Days 14, Day 28, Day 42, and Day 105
Secondary outcomes:
measure: Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)
timeFrame: 8 weeks
measure: Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)
timeFrame: 8 weeks
measure: Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)
timeFrame: 8 weeks
measure: Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)
timeFrame: 8 weeks
measure: Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)
timeFrame: 8 weeks
measure: Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)
timeFrame: 8 weeks
measure: Occurrence of Hypoglycemia During Fasting Challenge
timeFrame: 8 Weeks
measure: Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)
timeFrame: 8 weeks
measure: Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)
timeFrame: 8 weeks
measure: Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)
timeFrame: 8 weeks
measure: Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Sofia
country: Bulgaria
facility: SHAT Children diseases "Prof. Dr. Ivan Mitov"
city: Varna
country: Bulgaria
facility: Medical University of Varna UMHAT "St. Marina"
city: Monteral
country: Canada
facility: Research Institute of the McGill University Health Centre
state: Qubec
city: Odense
country: Denmark
facility: Odense University Hospital
city: Tbilisi
country: Georgia
facility: LTD "Pediatric Surgery Centre"
city: Magdeburg
country: Germany
facility: Magdeburg University Clinic Center (Otto-von-Guericke Universität)
city: Ramat Gan
country: Israel
facility: Edmond & Lilly Safra's Children Hospital
state: Tel-Hashomer
city: Jerusalem
country: Israel
facility: Hadassah Har Hazofim MC - Division of Pediatric Endocrinology
city: Moscow
country: Russian Federation
facility: Endocrinology research center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d' Hebron
city: Sarıçam
country: Turkey
facility: Adana Cukurova University Balcalı Hospital
state: Adana
city: Çankaya
country: Turkey
facility: Hacettepe University
state: Ankara
city: Kayapinar
country: Turkey
facility: SBÜ Gazi Yaşargil Eğitim ve Araştirma Hastanesi
state: Diyarbakir
city: Yakutiye
country: Turkey
facility: Erzurum City Hospital
state: Erzurum
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
References: