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

Primary Purpose

Congenital Hyperinsulinism

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RZ358 Sequential Group Cohort 1
RZ358 Sequential Group Cohort 2
RZ358 Sequential Group Cohort 3
RZ358 Sequential Group Cohort 4
Sponsored by
Rezolute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Hyperinsulinism focused on measuring Hypoglycemia, Congenital Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases, Pancreatic Diseases, Digestive System Diseases, Hyperinsulinism

Eligibility Criteria

2 Years - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Children's Hospital of Philadelphia
  • Cook Children's Medical Center
  • SHAT Children diseases "Prof. Dr. Ivan Mitov"
  • Medical University of Varna UMHAT "St. Marina"
  • Research Institute of the McGill University Health Centre
  • Odense University Hospital
  • LTD "Pediatric Surgery Centre"
  • Magdeburg University Clinic Center (Otto-von-Guericke Universität)
  • Edmond & Lilly Safra's Children Hospital
  • Hadassah Har Hazofim MC - Division of Pediatric Endocrinology
  • Endocrinology research center
  • Hospital Universitari Vall d' Hebron
  • Adana Cukurova University Balcalı Hospital
  • Hacettepe University
  • SBÜ Gazi Yaşargil Eğitim ve Araştirma Hastanesi
  • Erzurum City Hospital
  • Great Ormond Street Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

RZ358 Cohort 1

RZ358 Cohort 2

RZ358 Cohort 3

RZ358 Cohort 4

Arm Description

Outcomes

Primary Outcome Measures

Glycemic efficacy: Target glucose control
Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)
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.
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).

Secondary Outcome Measures

Glycemic efficacy: Occurrence of hypoglycemia
Change from Baseline in the Incidence of Hypoglycemia by Self-Monitored Blood Glucose (SMBG)
Glycemic efficacy: Duration of Hypoglycemia
Change from Baseline in the Absolute (minutes) and Percent Time with Hypoglycemia by CGM
Glycemic efficacy: Occurrence of Hypoglycemia
Change from Baseline in the Incidence of Hypoglycemia by CGM
Overnight Target Glucose Control
Change from Baseline in Percent Time in Overnight (midnight to 8 am) Glucose Target Range by CGM
Glycemic Efficacy: Ability to Complete a Fast without Hypoglycemia
Change from Baseline in Incidence of Hypoglycemia by SMBG, During a 12-hour Fasting Challenge

Full Information

First Posted
August 21, 2020
Last Updated
September 7, 2022
Sponsor
Rezolute
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1. Study Identification

Unique Protocol Identification Number
NCT04538989
Brief Title
An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
Official Title
An Open-Label Multiple-Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
February 24, 2020 (Actual)
Primary Completion Date
April 5, 2022 (Actual)
Study Completion Date
August 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rezolute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Hyperinsulinism
Keywords
Hypoglycemia, Congenital Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases, Pancreatic Diseases, Digestive System Diseases, Hyperinsulinism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RZ358 Cohort 1
Arm Type
Experimental
Arm Title
RZ358 Cohort 2
Arm Type
Experimental
Arm Title
RZ358 Cohort 3
Arm Type
Experimental
Arm Title
RZ358 Cohort 4
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
RZ358 Sequential Group Cohort 1
Intervention Description
IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)
Intervention Type
Drug
Intervention Name(s)
RZ358 Sequential Group Cohort 2
Intervention Description
IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)
Intervention Type
Drug
Intervention Name(s)
RZ358 Sequential Group Cohort 3
Intervention Description
IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Intervention Type
Drug
Intervention Name(s)
RZ358 Sequential Group Cohort 4
Intervention Description
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)
Primary Outcome Measure Information:
Title
Glycemic efficacy: Target glucose control
Description
Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)
Time Frame
8 weeks
Title
Repeat dose safety and tolerability of RZ358
Description
Occurrence of a safety signal as assessed by the incidence of treatment-emergent AEs, SAEs, and AEs leading to study drug discontinuation.
Time Frame
Through 21 Weeks
Title
Repeat dose pharmacokinetics of RZ358
Description
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).
Time Frame
Through 8 weeks
Secondary Outcome Measure Information:
Title
Glycemic efficacy: Occurrence of hypoglycemia
Description
Change from Baseline in the Incidence of Hypoglycemia by Self-Monitored Blood Glucose (SMBG)
Time Frame
8 weeks
Title
Glycemic efficacy: Duration of Hypoglycemia
Description
Change from Baseline in the Absolute (minutes) and Percent Time with Hypoglycemia by CGM
Time Frame
8 weeks
Title
Glycemic efficacy: Occurrence of Hypoglycemia
Description
Change from Baseline in the Incidence of Hypoglycemia by CGM
Time Frame
8 weeks
Title
Overnight Target Glucose Control
Description
Change from Baseline in Percent Time in Overnight (midnight to 8 am) Glucose Target Range by CGM
Time Frame
8 weeks
Title
Glycemic Efficacy: Ability to Complete a Fast without Hypoglycemia
Description
Change from Baseline in Incidence of Hypoglycemia by SMBG, During a 12-hour Fasting Challenge
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
SHAT Children diseases "Prof. Dr. Ivan Mitov"
City
Sofia
Country
Bulgaria
Facility Name
Medical University of Varna UMHAT "St. Marina"
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
Facility Name
Research Institute of the McGill University Health Centre
City
Monteral
State/Province
Qubec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
LTD "Pediatric Surgery Centre"
City
Tbilisi
ZIP/Postal Code
0122
Country
Georgia
Facility Name
Magdeburg University Clinic Center (Otto-von-Guericke Universität)
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
Edmond & Lilly Safra's Children Hospital
City
Ramat Gan
State/Province
Tel-Hashomer
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Hadassah Har Hazofim MC - Division of Pediatric Endocrinology
City
Jerusalem
ZIP/Postal Code
90000
Country
Israel
Facility Name
Endocrinology research center
City
Moscow
ZIP/Postal Code
117036
Country
Russian Federation
Facility Name
Hospital Universitari Vall d' Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Adana Cukurova University Balcalı Hospital
City
Sarıçam
State/Province
Adana
Country
Turkey
Facility Name
Hacettepe University
City
Çankaya
State/Province
Ankara
ZIP/Postal Code
06800
Country
Turkey
Facility Name
SBÜ Gazi Yaşargil Eğitim ve Araştirma Hastanesi
City
Kayapinar
State/Province
Diyarbakir
ZIP/Postal Code
21070
Country
Turkey
Facility Name
Erzurum City Hospital
City
Yakutiye
State/Province
Erzurum
Country
Turkey
Facility Name
Great Ormond Street Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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