Clinical trial NCT06208215: RZ358 Treatment for Congenital Hyperinsulinism
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Evaluate the Efficacy and Safety of RZ358 in Patients with Congenital Hyperinsulinism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Congenital Hyperinsulinism
Keywords: Hypoglycemia
Congenital Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Hyperinsulinism
Lead sponsor: Rezolute
Sponsor class: OTHER
First posted: 2024-01-17
Enrollment: 56
Sex: ALL
Minimum age (years): 3
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Glycemic efficacy: Target glucose control
timeFrame: 24 weeks
Secondary outcomes:
measure: Glycemic efficacy: Occurrence of hypoglycemia
timeFrame: 24 weeks
measure: Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism
timeFrame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period
measure: Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism, Laboratory tests evaluated for significant changes from baseline by treated groups
timeFrame: Time Frame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period
measure: Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG)
timeFrame: 24 weeks
measure: Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG) Weekly Assessment
timeFrame: 24 weeks
measure: Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Daily Assessment
timeFrame: 24 weeks
measure: Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Overnight Assessment
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Varna
country: Bulgaria
facility: Rezolute Investigative Site, Varna, Bulgaria
city: Montreal
country: Canada
facility: Rezolute Investigative Site, Montreal, Canada,
state: Quebec
city: Saskatoon
country: Canada
facility: Rezolute Investigative Site, Saskatoon, Canada
city: Odense
country: Denmark
facility: Rezolute Investigative Site, Odense, Denmark
city: Bron
country: France
facility: Rezolute Investigative Site, Bron, France
city: Paris
country: France
facility: Rezolute Investigative Site, Paris, France
city: Tbilisi
country: Georgia
facility: Rezolute Investigative Site, Tbilisi, Georgia
city: Berlin
country: Germany
facility: Rezolute Investigative Site, Berlin, Germany
city: Dusseldorf
country: Germany
facility: Rezolute Investigative Site, Dusseldorf, Germany
city: Athens
country: Greece
facility: Rezolute Investigative Site, Athens, Greece
city: Ramat Gan
country: Israel
facility: Rezolute Investigative Site, Ramat Gan, Israel
city: Seeb
country: Oman
facility: Rezolute Investigative Site, Seeb, Oman
city: Al Rayyan
country: Qatar
facility: Rezolute Investigative Site, Al Rayyan, Qatar
city: Riyad
country: Saudi Arabia
facility: Rezolute Investigative Site, Riyad, Saudi Arabia
city: Riyad
country: Saudi Arabia
facility: Rezolute Investigative Site, Riyad, Saudi Arabia
city: Barcelona
country: Spain
facility: Rezolute Investigative Site, Barcelona, Spain
city: Sevilla
country: Spain
facility: Rezolute Investigative Site, Sevilla, Spain
city: Ankara
country: Turkey
facility: Rezolute Investigative Site, Ankara, Turkey
city: Al Mafraq
country: United Arab Emirates
facility: Rezolute Investigative Site, Al Mafraq, United Arab Emirates
city: London
country: United Kingdom
facility: Rezolute Investigative Site, London, United Kingdom
city: Manchester
country: United Kingdom
facility: Rezolute Investigative Site, Manchester, United Kingdom
city: Hà Nội
country: Vietnam
facility: Rezolute Investigative Site, Hà Nội, Vietnam
Study officials:
affiliation: Rezolute
name: Gopal Saha, MD
role: STUDY_DIRECTOR
References: