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

Sponsor

Rezolute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04538989

Collaborator

(none)

Enrollment

Locations

Arms

27.2

Anticipated Duration (Months)

1.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Congenital Hyperinsulinism	Drug: RZ358 Sequential Group Cohort 1 Drug: RZ358 Sequential Group Cohort 2 Drug: RZ358 Sequential Group Cohort 3 Drug: RZ358 Sequential Group Cohort 4	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 24, 2020

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

Glycemic efficacy: Target glucose control [8 weeks]
Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)
Repeat dose safety and tolerability of RZ358 [Through 21 Weeks]
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 [Through 8 weeks]
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 [8 weeks]
Change from Baseline in the Incidence of Hypoglycemia by Self-Monitored Blood Glucose (SMBG)
Glycemic efficacy: Duration of Hypoglycemia [8 weeks]
Change from Baseline in the Absolute (minutes) and Percent Time with Hypoglycemia by CGM
Glycemic efficacy: Occurrence of Hypoglycemia [8 weeks]
Change from Baseline in the Incidence of Hypoglycemia by CGM
Overnight Target Glucose Control [8 weeks]
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 [8 weeks]
Change from Baseline in Incidence of Hypoglycemia by SMBG, During a 12-hour Fasting Challenge

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 45 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

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