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

NCT04538989 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: RZ358-606
• Study Type: interventional
• Target: 23
• Locations: 11 countries
• Sites: 17

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).

Conditions

Congenital Hyperinsulinism

Keywords

Hypoglycemia; Congenital Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases; Hyperinsulinism

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)

  8 weeks

• Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)

  8 weeks

• Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)

  8 weeks

• Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)

  8 weeks

• Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)

  8 weeks

Study Arms (4)

RZ358 Cohort 1

EXPERIMENTAL

Drug: RZ358 Sequential Group Cohort 1

RZ358 Cohort 2

EXPERIMENTAL

Drug: RZ358 Sequential Group Cohort 2

RZ358 Cohort 3

EXPERIMENTAL

Drug: RZ358 Sequential Group Cohort 3

RZ358 Cohort 4

EXPERIMENTAL

Drug: RZ358 Sequential Group Cohort 4

Interventions

RZ358 Sequential Group Cohort 1 DRUG

IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)

RZ358 Cohort 1

RZ358 Sequential Group Cohort 2 DRUG

IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)

RZ358 Cohort 2

RZ358 Sequential Group Cohort 3 DRUG

IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)

RZ358 Cohort 3

RZ358 Sequential Group Cohort 4 DRUG

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)

RZ358 Cohort 4

Eligibility Criteria

• Age: 2 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rezolute: lead

Study Sites (17)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

SHAT Children diseases "Prof. Dr. Ivan Mitov"

Sofia, Bulgaria

Location

Medical University of Varna UMHAT "St. Marina"

Varna, 9010, Bulgaria

Location

Research Institute of the McGill University Health Centre

Monteral, Qubec, H4A 3J1, Canada

Location

Odense University Hospital

Odense, 5000, Denmark

Location

LTD "Pediatric Surgery Centre"

Tbilisi, 0122, Georgia

Location

Magdeburg University Clinic Center (Otto-von-Guericke Universität)

Magdeburg, 39120, Germany

Location

Edmond & Lilly Safra's Children Hospital

Ramat Gan, Tel-Hashomer, 5265601, Israel

Location

Hadassah Har Hazofim MC - Division of Pediatric Endocrinology

Jerusalem, 90000, Israel

Location

Endocrinology research center

Moscow, 117036, Russia

Location

Hospital Universitari Vall d' Hebron

Barcelona, 08035, Spain

Location

Adana Cukurova University Balcalı Hospital

Sarıçam, Adana, Turkey (Türkiye)

Location

Hacettepe University

Çankaya, Ankara, 06800, Turkey (Türkiye)

Location

SBÜ Gazi Yaşargil Eğitim ve Araştirma Hastanesi

Kayapınar, Diyarbakır, 21070, Turkey (Türkiye)

Location

Erzurum City Hospital

Yakutiye, Erzurum, Turkey (Türkiye)

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Related Publications (1)

• Demirbilek H, Melikyan M, Iotova V, Galcheva S, Ozbek MN, Dastamani A, Kheladze N, Mazor-Aronovitch K, Clemente M, Empting S, Mohnike K, Christesen HT, Thornton PS, De Leon DD, Hood D, O'Boyle E, Roberts BK. Global, multi-center, repeat-dose, phase 2 study of RZ358 (ersodetug), an insulin receptor antibody, for congenital hyperinsulinism. Med. 2025 Jun 13;6(6):100611. doi: 10.1016/j.medj.2025.100611. Epub 2025 Mar 18.

  PMID: 40107271 DERIVED

MeSH Terms

Conditions

Congenital Hyperinsulinism; Hypoglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases; Hyperinsulinism

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Limitations and Caveats

Limitations include a small sample size (low statistical power), an open-label design (potential for bias due to lack of blinding), a short treatment period in a chronic disease, and a lack of ethnic diversity in study participants who have a rare pediatric disease. Additionally, the COVID-19 pandemic impacted the study by causing a delay in projected enrollment and study timelines. However, due to excess precaution taken, there was no impact on the overall execution/outcomes of the study.

Results Point of Contact

• Title: Chief Medical Officer (Dr. Brian Roberts)
• Organization: Rezolute

brian@rezolutebio.com

650-206-4507

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: September 4, 2020
• Study Start: February 24, 2020
• Primary Completion: April 5, 2022
• Study Completion: August 19, 2022
• Last Updated: May 28, 2025
• Results First Posted: May 28, 2025

Record last verified: 2025-05

Locations

IL (2); GE (1); DE (1); ES (1); TU (4); CA (1); US (2); GB (1); BU (2); DK (1); RU (1)