RZ358 Treatment for Congenital Hyperinsulinism (sunRIZE)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Evaluate the Efficacy and Safety of RZ358 in Patients With Congenital Hyperinsulinism

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.

Study Overview

• Status: Recruiting
• Conditions: Congenital Hyperinsulinism
• Intervention / Treatment: Drug: RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOC; Drug: RZ358 (10 mg/kg) or Placebo + SOC; Drug: RZ358 (5-10 mg/kg) + SOC

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.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Davelyn Hood, MD; Phone Number: 6502064507; Email: clinicaltrials@rezolutebio.com
• Study Contact Backup: Name: Gopal Saha, MD; Phone Number: 6502064507; Email: clinicaltrials@rezolutebio.com

Study Locations

• Bulgaria
  • Varna, Bulgaria, 9010
    • Not yet recruiting
    • Rezolute Investigative Site, Varna, Bulgaria
• Canada
  • Saskatoon, Canada, S7N 0W8
    • Not yet recruiting
    • Rezolute Investigative Site, Saskatoon, Canada
• Denmark
  • Odense, Denmark, 5000
    • Not yet recruiting
    • Rezolute Investigative Site, Odense, Denmark
• France
  • Bron, France, 69677
    • Not yet recruiting
    • Rezolute Investigative Site, Bron, France
  • Paris, France, 75015
    • Recruiting
    • Rezolute Investigative Site, Paris, France
• Georgia
  • Tbilisi, Georgia, 0159
    • Recruiting
    • Rezolute Investigative Site, Tbilisi, Georgia
• Germany
  • Berlin, Germany, 13353
    • Not yet recruiting
    • Rezolute Investigative Site, Berlin, Germany
  • Dusseldorf, Germany, 40225
    • Not yet recruiting
    • Rezolute Investigative Site, Dusseldorf, Germany
• Greece
  • Athens, Greece, 115 27
    • Not yet recruiting
    • Rezolute Investigative Site, Athens, Greece
• Israel
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Rezolute Investigative Site, Ramat Gan, Israel
• Oman
  • Seeb, Oman, 123
    • Not yet recruiting
    • Rezolute Investigative Site, Seeb, Oman
• Qatar
  • Al Rayyan, Qatar
    • Not yet recruiting
    • Rezolute Investigative Site, Al Rayyan, Qatar
• Saudi Arabia
  • Riyad, Saudi Arabia, 11426
    • Not yet recruiting
    • Rezolute Investigative Site, Riyad, Saudi Arabia
  • Riyad, Saudi Arabia, 11471
    • Not yet recruiting
    • Rezolute Investigative Site, Riyad, Saudi Arabia
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Rezolute Investigative Site, Barcelona, Spain
  • Sevilla, Spain, 41013
    • Not yet recruiting
    • Rezolute Investigative Site, Sevilla, Spain
• Turkey
  • Ankara, Turkey, 06800
    • Not yet recruiting
    • Rezolute Investigative Site, Ankara, Turkey
• United Arab Emirates
  • Al Mafraq, United Arab Emirates, 11001
    • Not yet recruiting
    • Rezolute Investigative Site, Al Mafraq, United Arab Emirates
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Not yet recruiting
    • Rezolute Investigative Site, London, United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Not yet recruiting
    • Rezolute Investigative Site, Manchester, United Kingdom
• Vietnam
  • Hà Nội, Vietnam, 100000
    • Not yet recruiting
    • Rezolute Investigative Site, Hà Nội, Vietnam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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	Drug: 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
Placebo Comparator: SoC + RZ358 (10 mg/kg) or Placebo; Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo	Drug: RZ358 (10 mg/kg) or Placebo + SOC; Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo
Experimental: 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	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic efficacy: Occurrence of hypoglycemia	Change in average daily percent time in hypoglycemia from baseline by Continuous Glucose Monitor (CGM)	24 weeks
Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism	Treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) captured per Common Terminology Criteria for Adverse Events (CTCAE) guidelines and coadded per Medical Dictionary for Regulatory Activities (MedDRA) will be summarized by system organ class, preferred term, and analyzed by number and percentage of events by treatment groups. Hepatic ultrasound: evaluated for significant structural changes (e.g. peliosis Hepatitis) Immunogenicity assessments: Blood samples for anti-drug antibody to RZ358 will be evaluated based on the titer, and potential neutralization effects. Hyperglycemia events: Will be evaluated by SMBG at thresholds of >250 mg/dL and >300 mg/dL and summarized by the treatment groups.	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	Laboratory parameters: ALT (U/L), AST (U/L), and ALP (U/L) will be evaluated for any significant changes from baseline (>3x ULN) by treatment groups. Vital Signs: blood pressure (mm of Hg), heart rate (beats/minute), and respiration (rate/minute) will be evaluated for any significant changes from baseline by treatment groups. ECG: heart rate (beats/minute), PR (milliseconds), QTcF intervals (milliseconds) will be evaluated for any significant changes from baseline by treatment groups.	Time Frame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period
Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG)	Proportion of participants experiencing no potentially serious hypoglycemia events by SMBG.	24 weeks
Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG) Weekly Assessment	Change in average weekly incidence of potentially serious hypoglycemia events by Self-Monitoring Blood Glucose (SMBG).	24 weeks
Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Daily Assessment	Change in average daily percent time with potentially serious hypoglycemia by Continuous Glucose Monitor (CGM).	24 weeks
Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Overnight Assessment	Change in average 8-hour overnight percent time with hypoglycemia by CGM. Change in average daily duration (min) with hypoglycemia by CGM. Proportion of participants achieving <4% average daily time in by CGM	24 weeks

Collaborators and Investigators

• Sponsor: Rezolute
• Investigators: Study Director: Gopal Saha, MD, Rezolute

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): April 4, 2025
• Study Completion (Estimated): September 28, 2026

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Hypoglycemia; Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Pancreatic Diseases; Congenital Hyperinsulinism; Hyperinsulinism
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Hypoglycemia; Hyperinsulinism; Congenital Hyperinsulinism; Nesidioblastosis
• Other Study ID Numbers: RZ358-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes