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' Hebron
• 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: 7 months to 43 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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
Glycemic efficacy: Target glucose control	Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)	8 weeks
Repeat dose safety and tolerability of RZ358	Occurrence of a safety signal as assessed by the incidence of treatment-emergent AEs, SAEs, and AEs leading to study drug discontinuation.	Through 21 Weeks
Repeat dose pharmacokinetics of RZ358	Change from baseline in RZ358 drug exposure as assessed by Population-PK modeling of maximum concentrations (Cmax) and Area under the Concentration-Time Curve (AUC).	Through 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic efficacy: Occurrence of hypoglycemia	Change from Baseline in the Incidence of Hypoglycemia by Self-Monitored Blood Glucose (SMBG)	8 weeks
Glycemic efficacy: Duration of Hypoglycemia	Change from Baseline in the Absolute (minutes) and Percent Time with Hypoglycemia by CGM	8 weeks
Glycemic efficacy: Occurrence of Hypoglycemia	Change from Baseline in the Incidence of Hypoglycemia by CGM	8 weeks
Overnight Target Glucose Control	Change from Baseline in Percent Time in Overnight (midnight to 8 am) Glucose Target Range by CGM	8 weeks
Glycemic Efficacy: Ability to Complete a Fast without Hypoglycemia	Change from Baseline in Incidence of Hypoglycemia by SMBG, During a 12-hour Fasting Challenge	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): September 8, 2022
• Last Update Submitted That Met QC Criteria: September 7, 2022
• Last Verified: June 1, 2021

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: RZ358-606

Drug and device information, study documents

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