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

Phase 2

Completed

Conditions: Congenital Hyperinsulinism

Interventions: Drug: RZ358 Sequential Group Cohort 3
Drug: RZ358 Sequential Group Cohort 1
Drug: RZ358 Sequential Group Cohort 2
Drug: RZ358 Sequential Group Cohort 4

Registration Number: NCT04538989

Lead Sponsor: Rezolute

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

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 & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
RZ358 Cohort 3	RZ358 Sequential Group Cohort 3	-
RZ358 Cohort 1	RZ358 Sequential Group Cohort 1	-
RZ358 Cohort 2	RZ358 Sequential Group Cohort 2	-
RZ358 Cohort 4	RZ358 Sequential Group Cohort 4	-

Primary Outcome Measures

Name	Time	Method
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)	8 weeks	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.
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)	8 weeks	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.
Repeat Dose Pharmacokinetics of RZ358	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	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.

Secondary Outcome Measures

Name	Time	Method
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)	8 weeks	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.
Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)	8 weeks	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.
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)	8 weeks	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.
Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)	8 weeks	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.
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)	8 weeks	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.
Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)	8 weeks	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.
Occurrence of Hypoglycemia During Fasting Challenge	8 Weeks	The occurrence of hypoglycemia during a 12 Hour fasting challenge.
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)	8 weeks	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.
Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)	8 weeks	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.
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)	8 weeks	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.
Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)	8 weeks	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.

Trial Locations

Locations (17): The Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
SHAT Children diseases "Prof. Dr. Ivan Mitov"
🇧🇬
Sofia, Bulgaria
Medical University of Varna UMHAT "St. Marina"
🇧🇬
Varna, Bulgaria
Research Institute of the McGill University Health Centre
🇨🇦
Monteral, Qubec, Canada
Odense University Hospital
🇩🇰
Odense, Denmark
LTD "Pediatric Surgery Centre"
🇬🇪
Tbilisi, Georgia
Magdeburg University Clinic Center (Otto-von-Guericke Universität)
🇩🇪
Magdeburg, Germany
Edmond & Lilly Safra's Children Hospital
🇮🇱
Ramat Gan, Tel-Hashomer, Israel
Hadassah Har Hazofim MC - Division of Pediatric Endocrinology
🇮🇱
Jerusalem, Israel
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The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States