RZ358 Treatment for Congenital Hyperinsulinism

NCT ID: NCT06208215

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-11
• Study Completion Date: 2027-11-14

Brief Summary

The Phase 3 pivotal study is designed to evaluate the efficacy and safety of RZ358 for the treatment of congenital hyperinsulinism (HI) as add-on to standard-of-care (SOC) therapy compared to SOC alone over 24 weeks and to evaluate the longer-term safety and efficacy of RZ358 during a subsequent open-label extension (OLE) period.

Detailed Description

Congenital hyperinsulinism (HI) is the most common cause of recurrent hypoglycemia in neonates and infants with an incidence of approximately 1 in 25,000 to 1 in 50,000 live births in the general population, and as high as 1 in 2,500 in certain populations with substantial consanguinity. Despite improved recognition, there is no satisfactory treatment or cure for congenital HI. Current medical therapies for congenital HI are directed at reducing or eliminating insulin production and/or secretion from the beta-cell. These current medications, however, achieve suboptimal glycemic control and/or have undesirable side effects. A therapy which safely and effectively attenuates the activity of insulin would address an important unmet need for these and other conditions associated with HI. This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled (SOC alone), parallel-arm, efficacy, and safety study of RZ358 in participants with congenital HI who have not achieved adequate hypoglycemia control with reasonable attempts at using usual SOC medical therapy. The study will randomize approximately 48 participants (≥1 year to ≤45 years of age) in a 1:1 ratio into 2 dosing arms (5 or 10 mg/kg with) and further randomize participants within each dosing level in a 2:1 ratio to receive RZ358 as add-on to SOC or placebo as add-on to SOC. An additional open-label (OL) arm will be conducted in parallel for participants who are ≥3 months to <1 year old (n=8), Upon completion of the pivotal treatment period (24-weeks), participants may roll-over to the OLE period at the discretion of the investigator and Sponsor.

Conditions

Congenital Hyperinsulinism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

SoC (Standard-of-Care) + RZ358 (5 mg/kg) or Placebo

Participants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo

Group Type: PLACEBO_COMPARATOR

RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOC

Intervention Type: DRUG

Participants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo

SoC + RZ358 (10 mg/kg) or Placebo

Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo

Group Type: PLACEBO_COMPARATOR

RZ358 (10 mg/kg) or Placebo + SOC

Intervention Type: DRUG

Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo

Open Label Arm, SoC + RZ358 (start 5mg/kg and increase to 10 mg/kg per protocol schedule

Infant participants from ≥3 months to \<1 year old who receive SOC therapy + RZ358 starting at 5 mg/kg and increasing to 10 mg/kg of RZ358, as needed, per the protocol schedule

Group Type: EXPERIMENTAL

RZ358 (5-10 mg/kg) + SOC

Intervention Type: DRUG

Infant participants from ≥3 months to \<1 year old who receive SOC therapy + RZ358 starting at 5 mg/kg and increasing to 10 mg/kg of RZ358, as needed, per the protocol schedule

Interventions

RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOC

Participants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo

Intervention Type: DRUG

RZ358 (10 mg/kg) or Placebo + SOC

Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo

Intervention Type: DRUG

RZ358 (5-10 mg/kg) + SOC

Infant participants from ≥3 months to \<1 year old who receive SOC therapy + RZ358 starting at 5 mg/kg and increasing to 10 mg/kg of RZ358, as needed, per the protocol schedule

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

At screening, aged ≥ 3 months and ≤ 45 years old.

An established clinical diagnosis of congenital HI (hyperinsulinism), with or without identification of a known monogenic variant by genetic testing.

Participant has failed to achieve adequate glycemic control with appropriate and reasonable trials of locally accepted and available Standard of Care (SOC) medical therapies (e.g., diazoxide and somatostatin analogs (SSAs)) per the judgment of the investigator.

Experiencing ≥ 3 hypoglycemia events per week by screening Self-Monitoring Blood Glucose (SMBG) and average daily percent time with hypoglycemia of ≥ 8% of the monitored screening Continuous Glucose Monitor (CGM) time.

Exclusion Criteria

Alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), total bilirubin (TB), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) ≥ 1.5 × the upper limit of normal for the age-specific reference range, regardless of assessed significance.

Body mass index (BMI) ≥ 35 kg/m2 for participants aged 18 years and above, or BMI ≥ 99% (percentile) per Centers for Disease Control and Prevention growth charts for participants > 12 and < 18 years of age (no BMI exclusion for participants ≤ 12 years of age).

A known clinical diagnosis of diabetes or pre-diabetes, or a history of insulin dependency within 3 months of screening.

Average daily percent time with hyperglycemia ≥ 5% of the monitored screening continuous glucose monitoring (CGM) time.

Known allergy or sensitivity to RZ358 or any component of the drug.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rezolute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gopal Saha, MD

Role: STUDY_DIRECTOR

Rezolute

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Rezolute Investigative Site, Varna, Bulgaria

Varna, , Bulgaria

Rezolute Investigative Site, Odense, Denmark

Odense, , Denmark

Rezolute Investigative Site, Bron, France

Bron, , France

Rezolute Investigative Site, Paris, France

Paris, , France

Rezolute Investigative Site, Tbilisi, Georgia

Tbilisi, , Georgia

Rezolute Investigative Site, Berlin, Germany

Berlin, , Germany

Rezolute Investigative Site, Dusseldorf, Germany

Düsseldorf, , Germany

Rezolute Investigative Site, Athens, Greece

Athens, , Greece

Rezolute Investigative Site, Seeb, Oman

Seeb, , Oman

Rezolute Investigative Site, Al Rayyan, Qatar

Al Rayyan, , Qatar

Rezolute Investigative Site, Barcelona, Spain

Barcelona, , Spain

Rezolute Investigative Site, Sevilla, Spain

Seville, , Spain

Rezolute Investigative Site, Ankara, Turkey

Ankara, , Turkey (Türkiye)

Rezolute Investigative Site, London, United Kingdom

London, , United Kingdom

Rezolute Investigative Site, Manchester, United Kingdom

Manchester, , United Kingdom

Rezolute Investigative Site, Hà Nội, Vietnam

Hà Nội, , Vietnam

Countries

United States; Bulgaria; Denmark; France; Georgia; Germany; Greece; Oman; Qatar; Spain; Turkey (Türkiye); United Kingdom; Vietnam

Other Identifiers

RZ358-301

Identifier Type: -

Identifier Source: org_study_id