RZ358 Treatment for Congenital Hyperinsulinism

NCT06208215 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: RZ358-301
• Study Type: interventional
• Target: 56
• Locations: 13 countries
• Sites: 18

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.

Conditions

Congenital Hyperinsulinism

Keywords

Hypoglycemia; Congenital Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases; Hyperinsulinism

Outcome Measures

Primary Outcomes (1)

• Glycemic efficacy: Target glucose control

  Change in average weekly hypoglycemia events from baseline by point-of-care Self-Monitoring Blood Glucose (SMBG)

  24 weeks

Secondary Outcomes (7)

• Glycemic efficacy: Occurrence of hypoglycemia

  24 weeks

• Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism

  24 weeks, plus up to two years of Open-Label Extension (OLE) period

• Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism, Laboratory tests evaluated for significant changes from baseline by treated groups

  Time Frame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period

• Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG)

  24 weeks

• Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG) Weekly Assessment

  24 weeks

Study Arms (3)

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

PLACEBO COMPARATOR

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

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

SoC + RZ358 (10 mg/kg) or Placebo

PLACEBO COMPARATOR

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

Drug: RZ358 (10 mg/kg) or Placebo + SOC

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

EXPERIMENTAL

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

Drug: RZ358 (5-10 mg/kg) + SOC

Interventions

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

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

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

RZ358 (10 mg/kg) or Placebo + SOC DRUG

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

SoC + RZ358 (10 mg/kg) or Placebo

RZ358 (5-10 mg/kg) + SOC 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

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

Eligibility Criteria

• Age: 3 Months - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Rezolute: lead

Study Sites (18)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Rezolute Investigative Site, Varna, Bulgaria

Varna, 9010, Bulgaria

Location

Rezolute Investigative Site, Odense, Denmark

Odense, 5000, Denmark

Location

Rezolute Investigative Site, Bron, France

Bron, 69677, France

Location

Rezolute Investigative Site, Paris, France

Paris, 75015, France

Location

Rezolute Investigative Site, Tbilisi, Georgia

Tbilisi, 0159, Georgia

Location

Rezolute Investigative Site, Berlin, Germany

Berlin, 13353, Germany

Location

Rezolute Investigative Site, Dusseldorf, Germany

Düsseldorf, 40225, Germany

Location

Rezolute Investigative Site, Athens, Greece

Athens, 115 27, Greece

Location

Rezolute Investigative Site, Seeb, Oman

Seeb, 123, Oman

Location

Rezolute Investigative Site, Al Rayyan, Qatar

Al Rayyan, Qatar

Location

Rezolute Investigative Site, Barcelona, Spain

Barcelona, 08035, Spain

Location

Rezolute Investigative Site, Sevilla, Spain

Seville, 41013, Spain

Location

Rezolute Investigative Site, Ankara, Turkey

Ankara, 06800, Turkey (Türkiye)

Location

Rezolute Investigative Site, London, United Kingdom

London, WC1N 3JH, United Kingdom

Location

Rezolute Investigative Site, Manchester, United Kingdom

Manchester, M13 9WL, United Kingdom

Location

Rezolute Investigative Site, Hà Nội, Vietnam

Hà Nội, 100000, Vietnam

Location

MeSH Terms

Conditions

Congenital Hyperinsulinism; Hypoglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases; Hyperinsulinism

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Gopal Saha, MD

  Rezolute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: January 17, 2024
• Study Start: January 11, 2024
• Primary Completion: November 14, 2025
• Study Completion (Estimated): November 14, 2027
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

QA (1); ES (2); DE (2); FR (2); OM (1); TU (1); DK (1); US (2); GR (1); GB (2); VN (1); GE (1); BU (1)