An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism

Phase 2

Completed

Interventions: Drug: RZ358 Sequential Group Cohort 3
Drug: RZ358 Sequential Group Cohort 1
Drug: RZ358 Sequential Group Cohort 2
Drug: RZ358 Sequential Group Cohort 4

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.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Repeat dose safety and tolerability of RZ358	Through 21 Weeks	Occurrence of a safety signal as assessed by the incidence of treatment-emergent AEs, SAEs, and AEs leading to study drug discontinuation.
Glycemic efficacy: Target glucose control	8 weeks	Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)
Repeat dose pharmacokinetics of RZ358	Through 8 weeks	Change from baseline in RZ358 drug exposure as assessed by Population-PK modeling of maximum concentrations (Cmax) and Area under the Concentration-Time Curve (AUC).

Secondary Outcome Measures

Name	Time	Method
Glycemic efficacy: Occurrence of hypoglycemia	8 weeks	Change from Baseline in the Incidence of Hypoglycemia by Self-Monitored Blood Glucose (SMBG)
Glycemic efficacy: Duration of Hypoglycemia	8 weeks	Change from Baseline in the Absolute (minutes) and Percent Time with Hypoglycemia by CGM
Glycemic efficacy: Occurrence of Hypoglycemia	8 weeks	Change from Baseline in the Incidence of Hypoglycemia by CGM
Overnight Target Glucose Control	8 weeks	Change from Baseline in Percent Time in Overnight (midnight to 8 am) Glucose Target Range by CGM
Glycemic Efficacy: Ability to Complete a Fast without Hypoglycemia	8 weeks	Change from Baseline in Incidence of Hypoglycemia by SMBG, During a 12-hour Fasting Challenge

Locations (17): Medical University of Varna UMHAT "St. Marina"
🇧🇬
Varna, Bulgaria
SHAT Children diseases "Prof. Dr. Ivan Mitov"
🇧🇬
Sofia, Bulgaria
Odense University Hospital
🇩🇰
Odense, Denmark
Hacettepe University
🇹🇷
Çankaya, Ankara, Turkey
Edmond & Lilly Safra's Children Hospital
🇮🇱
Ramat Gan, Tel-Hashomer, Israel
Erzurum City Hospital
🇹🇷
Yakutiye, Erzurum, Turkey
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Great Ormond Street Hospital
🇬🇧
London, United Kingdom
LTD "Pediatric Surgery Centre"
🇬🇪
Tbilisi, Georgia
Adana Cukurova University Balcalı Hospital
🇹🇷
Sarıçam, Adana, Turkey
SBÜ Gazi Yaşargil Eğitim ve Araştirma Hastanesi
🇹🇷
Kayapinar, Diyarbakir, Turkey
Hadassah Har Hazofim MC - Division of Pediatric Endocrinology
🇮🇱
Jerusalem, Israel
Endocrinology research center
🇷🇺
Moscow, Russian Federation
Hospital Universitari Vall d' Hebron
🇪🇸
Barcelona, Spain
The Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Research Institute of the McGill University Health Centre
🇨🇦
Monteral, Qubec, Canada
Magdeburg University Clinic Center (Otto-von-Guericke Universität)
🇩🇪
Magdeburg, Germany