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

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

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

Study Overview

• Status: Completed
• Conditions: Congenital Hyperinsulinism
• Intervention / Treatment: Drug: RZ358 Sequential Group Cohort 1; Drug: RZ358 Sequential Group Cohort 2; Drug: RZ358 Sequential Group Cohort 3; Drug: RZ358 Sequential Group Cohort 4

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • SHAT Children diseases "Prof. Dr. Ivan Mitov"
  • Varna, Bulgaria, 9010
    • Medical University of Varna UMHAT "St. Marina"
• Canada
  • Qubec
    • Monteral, Qubec, Canada, H4A 3J1
      • Research Institute of the McGill University Health Centre
• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital
• Georgia
  • Tbilisi, Georgia, 0122
    • LTD "Pediatric Surgery Centre"
• Germany
  • Magdeburg, Germany, 39120
    • Magdeburg University Clinic Center (Otto-von-Guericke Universität)
• Israel
  • Jerusalem, Israel, 90000
    • Hadassah Har Hazofim MC - Division of Pediatric Endocrinology
  • Tel-Hashomer
    • Ramat Gan, Tel-Hashomer, Israel, 5265601
      • Edmond & Lilly Safra's Children Hospital
• Russian Federation
  • Moscow, Russian Federation, 117036
    • Endocrinology Research Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d' Hebrón
• Turkey
  • Adana
    • Sarıçam, Adana, Turkey
      • Adana Cukurova University Balcalı Hospital
  • Ankara
    • Çankaya, Ankara, Turkey, 06800
      • Hacettepe University
  • Diyarbakir
    • Kayapinar, Diyarbakir, Turkey, 21070
      • SBÜ Gazi Yaşargil Eğitim ve Araştirma Hastanesi
  • Erzurum
    • Yakutiye, Erzurum, Turkey
      • Erzurum City Hospital
• United Kingdom
  • London, United Kingdom
    • Great Ormond Street Hospital
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 41 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RZ358 Cohort 1	Drug: RZ358 Sequential Group Cohort 1; IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)
Experimental: RZ358 Cohort 2	Drug: RZ358 Sequential Group Cohort 2; IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)
Experimental: RZ358 Cohort 3	Drug: RZ358 Sequential Group Cohort 3; IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Experimental: RZ358 Cohort 4	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)	The median of average daily percent time within the glucose target range 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline and End of Treatment (EOT) is reported.	8 weeks
Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)	The average daily percent time within the glucose target range (70-180 mg/dL) is compared from baseline to end of treatment (EOT) and the median percent change of that difference is reported.	8 weeks
Repeat Dose Pharmacokinetics of RZ358	All patients who received RZ358 and for whom the primary PK data was considered to be sufficient and interpretable were to be included in the PK analyses. Individual and mean plasma concentration data is summarized descriptively at the specified timepoints. The results of this study may be combined with those of other studies for analysis and modeling (e.g., population PK and PK-PD), and therefore the PK parameters are reported separately, as part of an iterative population PK approach.	Pre dose Weeks 1,3,5,7, 1-hr post dose Week 1 and Week 7, and Follow up on Days 14, Day 28, Day 42, and Day 105

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)	The median of average weekly number of overall hypoglycemia events (<70 mg/dL [3.9mmol/L], moderate hypoglycemia events (<60 mg/dL [3.3 mmol/L] and severe hypoglycemia events (<50 mg/dL [2.8mmol/L]) by SMBG at baseline (BL) and end of treatment (EOT) is reported.	8 weeks
Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)	The average weekly number overall hypoglycemia events (<70 mg/dL [3.9mmol/L], moderate hypoglycemia events (<60 mg/dL [3.3 mmol/L] and severe hypoglycemia events (<50 mg/dL [2.8mmol/L]) by SMBG is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.	8 weeks
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)	The median of average daily percent time in overall (<70 mg/dL [<3.9 mmol/L]), moderate (<60 mg/dL [3.3 mmol/L]), and severe (<50 mg/dL [2.8 mmol/L]) hypoglycemia at baseline (BL) and end of treatment (EOT) is reported.	8 weeks
Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)	The average daily percent time in overall (<70 mg/dL [<3.9 mmol/L]), moderate (<60 mg/dL [3.3 mmol/L]), and severe (<50 mg/dL [2.8 mmol/L]) hypoglycemia is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.	8 weeks
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)	The median of average duration (minutes) in overall (<70 mg/dL [<3.9 mmol/L]), moderate (<60 mg/dL [3.3 mmol/L] ), and severe (<50 mg/dL [2.8 mmol/L]) hypoglycemia by CGM at baseline (BL) and end of treatment (EOT) is reported.	8 weeks
Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)	The average duration (minutes) in overall (<70 mg/dL [<3.9 mmol/L]), moderate (<60 mg/dL [3.3 mmol/L] ), and severe (<50 mg/dL [2.8 mmol/L]) hypoglycemia by CGM is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.	8 weeks
Occurrence of Hypoglycemia During Fasting Challenge	The occurrence of hypoglycemia during a 12 Hour fasting challenge.	8 Weeks
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)	The median of average hypoglycemia events per day at each of the specified glucose thresholds [<70, <60, and <50 mg/dL (3.9, 3.3, and 2.8 mmol/L)], by CGM at baseline (BL) and end of treatment (EOT) is reported.	8 weeks
Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)	The average hypoglycemia events per day at each of the specified glucose thresholds [<70, <60, and <50 mg/dL (3.9, 3.3, and 2.8 mmol/L)], by CGM is compared from baseline (BL) to end of treatment (EOT) and the median net changes of those differences are reported.	8 weeks
Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)	The median of average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) at baseline (BL) and end of treatment (EOT) is reported.	8 weeks
Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)	The average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) is compared from baseline (BL) to end of treeatment (EOT) and the median percent change of that difference is reported.	8 weeks

Collaborators and Investigators

• Sponsor: Rezolute

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): April 5, 2022
• Study Completion (Actual): August 19, 2022

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: August 31, 2020
• First Posted (Actual): September 4, 2020

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

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: Metabolic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Glucose Metabolism Disorders; Pancreatic Diseases; Hypoglycemia; Hyperinsulinism; Congenital Hyperinsulinism; Nesidioblastosis
• Other Study ID Numbers: RZ358-606

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No