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

NCT ID: NCT04538989

Last Updated: 2025-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-24
• Study Completion Date: 2022-08-19

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.

Conditions

Congenital Hyperinsulinism

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RZ358 Cohort 1

Group Type: EXPERIMENTAL

RZ358 Sequential Group Cohort 1

Intervention Type: DRUG

IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)

RZ358 Cohort 2

Group Type: EXPERIMENTAL

RZ358 Sequential Group Cohort 2

Intervention Type: DRUG

IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)

RZ358 Cohort 3

Group Type: EXPERIMENTAL

RZ358 Sequential Group Cohort 3

Intervention Type: DRUG

IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)

RZ358 Cohort 4

Group Type: EXPERIMENTAL

RZ358 Sequential Group Cohort 4

Intervention Type: DRUG

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)

Interventions

RZ358 Sequential Group Cohort 1

IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)

Intervention Type: DRUG

RZ358 Sequential Group Cohort 2

IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)

Intervention Type: DRUG

RZ358 Sequential Group Cohort 3

IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)

Intervention Type: DRUG

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)

Intervention Type: DRUG

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rezolute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

SHAT Children diseases "Prof. Dr. Ivan Mitov"

Sofia, , Bulgaria

Medical University of Varna UMHAT "St. Marina"

Varna, , Bulgaria

Research Institute of the McGill University Health Centre

Monteral, Qubec, Canada

Odense University Hospital

Odense, , Denmark

LTD "Pediatric Surgery Centre"

Tbilisi, , Georgia

Magdeburg University Clinic Center (Otto-von-Guericke Universität)

Magdeburg, , Germany

Edmond & Lilly Safra's Children Hospital

Ramat Gan, Tel-Hashomer, Israel

Hadassah Har Hazofim MC - Division of Pediatric Endocrinology

Jerusalem, , Israel

Endocrinology research center

Moscow, , Russia

Hospital Universitari Vall d' Hebron

Barcelona, , Spain

Adana Cukurova University Balcalı Hospital

Sarıçam, Adana, Turkey (Türkiye)

Hacettepe University

Çankaya, Ankara, Turkey (Türkiye)

SBÜ Gazi Yaşargil Eğitim ve Araştirma Hastanesi

Kayapınar, Diyarbakır, Turkey (Türkiye)

Erzurum City Hospital

Yakutiye, Erzurum, Turkey (Türkiye)

Great Ormond Street Hospital

London, , United Kingdom

Countries

United States; Bulgaria; Canada; Denmark; Georgia; Germany; Israel; Russia; Spain; Turkey (Türkiye); United Kingdom

References

Demirbilek H, Melikyan M, Iotova V, Galcheva S, Ozbek MN, Dastamani A, Kheladze N, Mazor-Aronovitch K, Clemente M, Empting S, Mohnike K, Christesen HT, Thornton PS, De Leon DD, Hood D, O'Boyle E, Roberts BK. Global, multi-center, repeat-dose, phase 2 study of RZ358 (ersodetug), an insulin receptor antibody, for congenital hyperinsulinism. Med. 2025 Jun 13;6(6):100611. doi: 10.1016/j.medj.2025.100611. Epub 2025 Mar 18.

Reference Type: DERIVED

PMID: 40107271 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RZ358-606

Identifier Type: -

Identifier Source: org_study_id