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

Congenital Hyperinsulinism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04538989
• Other study ID #: RZ358-606
• Status: Completed
• Phase: Phase 2
• Start date: February 24, 2020
• Est. completion date: August 19, 2022

Study information

• Verified date: June 2021
• Source: Rezolute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 19, 2022
• Est. primary completion date: April 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 45 Years

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

Related Conditions & MeSH terms

• Congenital Hyperinsulinism
• Hyperinsulinism
• Nesidioblastosis

Intervention

Drug:
• RZ358 Sequential Group Cohort 1
IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)
• RZ358 Sequential Group Cohort 2
IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)
• RZ358 Sequential Group Cohort 3
IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
• RZ358 Sequential Group Cohort 4
IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)

Locations

Country	Name	City	State
Bulgaria	SHAT Children diseases "Prof. Dr. Ivan Mitov"	Sofia
Bulgaria	Medical University of Varna UMHAT "St. Marina"	Varna
Canada	Research Institute of the McGill University Health Centre	Monteral	Qubec
Denmark	Odense University Hospital	Odense
Georgia	LTD "Pediatric Surgery Centre"	Tbilisi
Germany	Magdeburg University Clinic Center (Otto-von-Guericke Universität)	Magdeburg
Israel	Hadassah Har Hazofim MC - Division of Pediatric Endocrinology	Jerusalem
Israel	Edmond & Lilly Safra's Children Hospital	Ramat Gan	Tel-Hashomer
Russian Federation	Endocrinology research center	Moscow
Spain	Hospital Universitari Vall d' Hebron	Barcelona
Turkey	Hacettepe University	Çankaya	Ankara
Turkey	SBÜ Gazi Yasargil Egitim ve Arastirma Hastanesi	Kayapinar	Diyarbakir
Turkey	Adana Cukurova University Balcali Hospital	Sariçam	Adana
Turkey	Erzurum City Hospital	Yakutiye	Erzurum
United Kingdom	Great Ormond Street Hospital	London
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Rezolute

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Denmark,  Georgia,  Germany,  Israel,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic efficacy: Target glucose control	Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)	8 weeks
Primary	Repeat dose safety and tolerability of RZ358	Occurrence of a safety signal as assessed by the incidence of treatment-emergent AEs, SAEs, and AEs leading to study drug discontinuation.	Through 21 Weeks
Primary	Repeat dose pharmacokinetics of RZ358	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).	Through 8 weeks
Secondary	Glycemic efficacy: Occurrence of hypoglycemia	Change from Baseline in the Incidence of Hypoglycemia by Self-Monitored Blood Glucose (SMBG)	8 weeks
Secondary	Glycemic efficacy: Duration of Hypoglycemia	Change from Baseline in the Absolute (minutes) and Percent Time with Hypoglycemia by CGM	8 weeks
Secondary	Glycemic efficacy: Occurrence of Hypoglycemia	Change from Baseline in the Incidence of Hypoglycemia by CGM	8 weeks
Secondary	Overnight Target Glucose Control	Change from Baseline in Percent Time in Overnight (midnight to 8 am) Glucose Target Range by CGM	8 weeks
Secondary	Glycemic Efficacy: Ability to Complete a Fast without Hypoglycemia	Change from Baseline in Incidence of Hypoglycemia by SMBG, During a 12-hour Fasting Challenge	8 weeks