Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06208215
Other study ID # RZ358-301
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date January 11, 2024
Est. completion date September 28, 2026

Study information

Verified date February 2024
Source Rezolute
Contact Davelyn Hood, MD
Phone 6502064507
Email clinicaltrials@rezolutebio.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The Phase 3 pivotal study is designed to evaluate the efficacy and safety of RZ358 for the treatment of congenital hyperinsulinism (HI) as add-on to standard-of-care (SOC) therapy compared to SOC alone over 24 weeks and to evaluate the longer-term safety and efficacy of RZ358 during a subsequent open-label extension (OLE) period.


Description:

Congenital hyperinsulinism (HI) is the most common cause of recurrent hypoglycemia in neonates and infants with an incidence of approximately 1 in 25,000 to 1 in 50,000 live births in the general population, and as high as 1 in 2,500 in certain populations with substantial consanguinity. Despite improved recognition, there is no satisfactory treatment or cure for congenital HI. Current medical therapies for congenital HI are directed at reducing or eliminating insulin production and/or secretion from the beta-cell. These current medications, however, achieve suboptimal glycemic control and/or have undesirable side effects. A therapy which safely and effectively attenuates the activity of insulin would address an important unmet need for these and other conditions associated with HI. This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled (SOC alone), parallel-arm, efficacy, and safety study of RZ358 in participants with congenital HI who have not achieved adequate hypoglycemia control with reasonable attempts at using usual SOC medical therapy. The study will randomize approximately 48 participants (≥1 year to ≤45 years of age) in a 1:1 ratio into 2 dosing arms (5 or 10 mg/kg with) and further randomize participants within each dosing level in a 2:1 ratio to receive RZ358 as add-on to SOC or placebo as add-on to SOC. An additional open-label (OL) arm will be conducted in parallel for participants who are ≥3 months to <1 year old (n=8), Upon completion of the pivotal treatment period (24-weeks), participants may roll-over to the OLE period at the discretion of the investigator and Sponsor.


Recruitment information / eligibility

Status Recruiting
Enrollment 56
Est. completion date September 28, 2026
Est. primary completion date April 4, 2025
Accepts healthy volunteers No
Gender All
Age group 3 Months to 45 Years
Eligibility Inclusion Criteria: At screening, aged = 3 months and = 45 years old. An established clinical diagnosis of congenital HI (hyperinsulinism), with or without identification of a known monogenic variant by genetic testing. Participant has failed to achieve adequate glycemic control with appropriate and reasonable trials of locally accepted and available Standard of Care (SOC) medical therapies (e.g., diazoxide and somatostatin analogs (SSAs)) per the judgment of the investigator. Experiencing = 3 hypoglycemia events per week by screening Self-Monitoring Blood Glucose (SMBG) and average daily percent time with hypoglycemia of = 8% of the monitored screening Continuous Glucose Monitor (CGM) time. Exclusion Criteria: Alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), total bilirubin (TB), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) = 1.5 × the upper limit of normal for the age-specific reference range, regardless of assessed significance. Body mass index (BMI) = 35 kg/m2 for participants aged 18 years and above, or BMI = 99% (percentile) per Centers for Disease Control and Prevention growth charts for participants > 12 and < 18 years of age (no BMI exclusion for participants = 12 years of age). A known clinical diagnosis of diabetes or pre-diabetes, or a history of insulin dependency within 3 months of screening. Average daily percent time with hyperglycemia = 5% of the monitored screening continuous glucose monitoring (CGM) time. Known allergy or sensitivity to RZ358 or any component of the drug.

Study Design


Intervention

Drug:
RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOC
Participants =1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo
RZ358 (10 mg/kg) or Placebo + SOC
Participants =1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo
RZ358 (5-10 mg/kg) + SOC
Infant participants from =3 months to <1 year old who receive SOC therapy + RZ358 starting at 5 mg/kg and increasing to 10 mg/kg of RZ358, as needed, per the protocol schedule

Locations

Country Name City State
Bulgaria Rezolute Investigative Site, Varna, Bulgaria Varna
Canada Rezolute Investigative Site, Saskatoon, Canada Saskatoon
Denmark Rezolute Investigative Site, Odense, Denmark Odense
France Rezolute Investigative Site, Bron, France Bron
France Rezolute Investigative Site, Paris, France Paris
Georgia Rezolute Investigative Site, Tbilisi, Georgia Tbilisi
Germany Rezolute Investigative Site, Berlin, Germany Berlin
Germany Rezolute Investigative Site, Dusseldorf, Germany Dusseldorf
Greece Rezolute Investigative Site, Athens, Greece Athens
Israel Rezolute Investigative Site, Ramat Gan, Israel Ramat Gan
Oman Rezolute Investigative Site, Seeb, Oman Seeb
Qatar Rezolute Investigative Site, Al Rayyan, Qatar Al Rayyan
Saudi Arabia Rezolute Investigative Site, Riyad, Saudi Arabia Riyad
Saudi Arabia Rezolute Investigative Site, Riyad, Saudi Arabia Riyad
Spain Rezolute Investigative Site, Barcelona, Spain Barcelona
Spain Rezolute Investigative Site, Sevilla, Spain Sevilla
Turkey Rezolute Investigative Site, Ankara, Turkey Ankara
United Arab Emirates Rezolute Investigative Site, Al Mafraq, United Arab Emirates Al Mafraq
United Kingdom Rezolute Investigative Site, London, United Kingdom London
United Kingdom Rezolute Investigative Site, Manchester, United Kingdom Manchester
Vietnam Rezolute Investigative Site, Hà N?i, Vietnam Hà N?i

Sponsors (1)

Lead Sponsor Collaborator
Rezolute

Countries where clinical trial is conducted

Bulgaria,  Canada,  Denmark,  France,  Georgia,  Germany,  Greece,  Israel,  Oman,  Qatar,  Saudi Arabia,  Spain,  Turkey,  United Arab Emirates,  United Kingdom,  Vietnam, 

Outcome

Type Measure Description Time frame Safety issue
Primary Glycemic efficacy: Target glucose control Change in average weekly hypoglycemia events from baseline by point-of-care Self-Monitoring Blood Glucose (SMBG) 24 weeks
Secondary Glycemic efficacy: Occurrence of hypoglycemia Change in average daily percent time in hypoglycemia from baseline by Continuous Glucose Monitor (CGM) 24 weeks
Secondary Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism Treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) captured per Common Terminology Criteria for Adverse Events (CTCAE) guidelines and coadded per Medical Dictionary for Regulatory Activities (MedDRA) will be summarized by system organ class, preferred term, and analyzed by number and percentage of events by treatment groups.
Hepatic ultrasound: evaluated for significant structural changes (e.g. peliosis Hepatitis)
Immunogenicity assessments: Blood samples for anti-drug antibody to RZ358 will be evaluated based on the titer, and potential neutralization effects.
Hyperglycemia events: Will be evaluated by SMBG at thresholds of >250 mg/dL and >300 mg/dL and summarized by the treatment groups.
24 weeks, plus up to two years of Open-Label Extension (OLE) period
Secondary Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism, Laboratory tests evaluated for significant changes from baseline by treated groups Laboratory parameters: ALT (U/L), AST (U/L), and ALP (U/L) will be evaluated for any significant changes from baseline (>3x ULN) by treatment groups.
Vital Signs: blood pressure (mm of Hg), heart rate (beats/minute), and respiration (rate/minute) will be evaluated for any significant changes from baseline by treatment groups.
ECG: heart rate (beats/minute), PR (milliseconds), QTcF intervals (milliseconds) will be evaluated for any significant changes from baseline by treatment groups.
Time Frame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period
Secondary Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG) Proportion of participants experiencing no potentially serious hypoglycemia events by SMBG. 24 weeks
Secondary Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG) Weekly Assessment Change in average weekly incidence of potentially serious hypoglycemia events by Self-Monitoring Blood Glucose (SMBG). 24 weeks
Secondary Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Daily Assessment Change in average daily percent time with potentially serious hypoglycemia by Continuous Glucose Monitor (CGM). 24 weeks
Secondary Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Overnight Assessment Change in average 8-hour overnight percent time with hypoglycemia by CGM. Change in average daily duration (min) with hypoglycemia by CGM. Proportion of participants achieving <4% average daily time in by CGM 24 weeks
See also
  Status Clinical Trial Phase
Recruiting NCT02021604 - Fluorodopa F 18 in Congenital Hyperinsulinism and Insulinoma Phase 1
Recruiting NCT04732416 - HM15136 Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI) Phase 2
Completed NCT02937558 - CSI-Glucagon for Prevention of Hypoglycemia in Children With Congenital Hyperinsulinism Phase 2
Completed NCT02604485 - A Single-Dose Open-Label Study of XOMA 358 in Subjects With Congenital Hyperinsulinism Phase 2
Recruiting NCT04205604 - 18FluoroLDOPA PET Imaging for the Detection and Localization of Focal Congenital Hyperinsulinism Phase 2
Completed NCT00987168 - Sandostatine® LP and Hyperinsulinism Phase 2
Completed NCT00897676 - Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity Phase 1/Phase 2
Active, not recruiting NCT03941236 - Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon in Children With Congenital Hyperinsulinism Phase 3
Completed NCT03042416 - 18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety Phase 3
Completed NCT04172441 - Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism Phase 2/Phase 3
Recruiting NCT04706910 - 18F-DOPA II - PET Imaging Optimization Phase 3
Completed NCT03777176 - A Two-Period Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism Phase 3
Recruiting NCT03768518 - GLP-1 Receptor Expression in CHI
Completed NCT04538989 - An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism Phase 2
Completed NCT01070758 - Lanreotide Autogel Treatment of Patients With Congenital Hyperinsulinism of Infancy Phase 4
Completed NCT00674440 - Utility of [F-18] fluoroDOPA for Neonatal Hyperinsulinism Phase 2
Terminated NCT00835328 - Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia Phase 1/Phase 2
Completed NCT00571324 - Effect of Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism Phase 1/Phase 2
Withdrawn NCT03053284 - Pasireotide in Hyperinsulinemic Hypoglycemia Phase 2
No longer available NCT02835131 - Compassionate Use of SOM230 for Hyperinsulinemic/Hypoglycemia