Congenital HyperinsulinismPhase 3sunRIZENCT06208215
RZ358 Treatment for Congenital Hyperinsulinism
A Phase 3 study testing RZ358 (5-10 mg/kg) + SOC in people with Congenital Hyperinsulinism, run by Rezolute at 18 sites in 13 countries.
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… Read more about this study
- Who is it for?
- Ages 3 months to 45 years
- Conditions the study is for
- Congenital Hyperinsulinism
- What is being tested?
- RZ358 (5-10 mg/kg) + SOC
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 18 sitesin 13 countries
- Study dates
- 11 Jan 2024to 14 Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
18 sites in 13 countries.
18 sites in 13 countries
United States2 sites
Cook Children's Medical Center
Fort Worth, Texas, 76104
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
France2 sites
Rezolute Investigative Site, Bron, France
Bron, 69677
Rezolute Investigative Site, Paris, France
Paris, 75015
Germany2 sites
Rezolute Investigative Site, Berlin, Germany
Berlin, 13353
Rezolute Investigative Site, Dusseldorf, Germany
Düsseldorf, 40225
Spain2 sites
Rezolute Investigative Site, Barcelona, Spain
Barcelona, 08035
Rezolute Investigative Site, Sevilla, Spain
Seville, 41013
United Kingdom2 sites
Rezolute Investigative Site, London, United Kingdom
London, WC1N 3JH
Rezolute Investigative Site, Manchester, United Kingdom
Manchester, M13 9WL
Turkey (Türkiye)1 site
Rezolute Investigative Site, Ankara, Turkey
Ankara, 06800
About this study
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
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.
Read the 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.
- Conditions
- Congenital Hyperinsulinism
- Being tested
- RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOC, RZ358 (10 mg/kg) or Placebo + SOC, RZ358 (5-10 mg/kg) + SOC
- Keywords
- Hypoglycemia, Congenital Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases, Pancreatic Diseases, Digestive System Diseases, Hyperinsulinism
- Medical subject headings
- Congenital Hyperinsulinism, Hypoglycemia, Glucose Metabolism Disorders, Metabolic Diseases, Pancreatic Diseases, Digestive System Diseases, Hyperinsulinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOCDrug
Participants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo
RZ358 (10 mg/kg) or Placebo + SOCDrug
Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo
RZ358 (5-10 mg/kg) + SOCDrug
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
| Study group | Role | What they receive |
|---|---|---|
| SoC (Standard-of-Care) + RZ358 (5 mg/kg) or Placebo | Placebo comparator | Participants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo Receives: Drug: RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOC |
| SoC + RZ358 (10 mg/kg) or Placebo | Placebo comparator | Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo Receives: Drug: RZ358 (10 mg/kg) or Placebo + SOC |
| Open Label Arm, SoC + RZ358 (start 5mg/kg and increase to 10 mg/kg per protocol schedule | Experimental | 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 Receives: Drug: RZ358 (5-10 mg/kg) + SOC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycemic efficacy: Target glucose control
Change in average weekly hypoglycemia events from baseline by point-of-care Self-Monitoring Blood Glucose (SMBG)
Measured: 24 weeks
Secondary outcomes (7)
Glycemic efficacy: Occurrence of hypoglycemia
Change in average daily percent time in hypoglycemia from baseline by Continuous Glucose Monitor (CGM)
Measured: 24 weeks
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.
Measured: 24 weeks, plus up to two years of Open-Label Extension (OLE) period
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.
Measured: Time Frame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period
Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG)
Proportion of participants experiencing no potentially serious hypoglycemia events by SMBG.
Measured: 24 weeks
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).
Measured: 24 weeks
Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Daily Assessment
Change in average daily percent time with potentially serious hypoglycemia by Continuous Glucose Monitor (CGM).
Measured: 24 weeks
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
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start11 Jan 2024
- Primary completion14 Nov 2025
- Study completion14 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital HyperinsulinismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rezolute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gopal Saha, MD, Study director, Rezolute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06208215
- Sponsor's protocol ID
- RZ358-301
- Acronym
- sunRIZE
- Status last verified
- Jan 2026
- First submitted
- 6 Dec 2023
- Last updated
- 8 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06208215
- Acronym / sponsor ID
- sunRIZE / RZ358-301
- Conditions
- Congenital Hyperinsulinism
- Keywords
- Hypoglycemia, Congenital Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases, Pancreatic Diseases, Digestive System Diseases, Hyperinsulinism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- RezoluteUniversity, hospital or other
- Study start
- 11 Jan 2024 (actual)
- Primary completion
- 14 Nov 2025 (actual)
- Study completion
- 14 Nov 2027 (estimated)
- First posted
- 17 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SoC (Standard-of-Care) + RZ358 (5 mg/kg) or Placebo | Placebo comparator | Drug: RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOCParticipants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo |
| SoC + RZ358 (10 mg/kg) or Placebo | Placebo comparator | Drug: RZ358 (10 mg/kg) or Placebo + SOCParticipants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo |
| Open Label Arm, SoC + RZ358 (start 5mg/kg and increase to 10 mg/kg per protocol schedule | Experimental | Drug: RZ358 (5-10 mg/kg) + SOCInfant 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 |
Who may qualify
- Ages
- 3 months to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOCParticipants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo | Drug | SoC (Standard-of-Care) + RZ358 (5 mg/kg) or Placebo |
| RZ358 (10 mg/kg) or Placebo + SOCParticipants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo | Drug | SoC + RZ358 (10 mg/kg) or Placebo |
| RZ358 (5-10 mg/kg) + SOCInfant 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 | Drug | Open Label Arm, SoC + RZ358 (start 5mg/kg and increase to 10 mg/kg per protocol schedule |
Primary outcome
Glycemic efficacy: Target glucose control
Time frame: 24 weeks
Change in average weekly hypoglycemia events from baseline by point-of-care Self-Monitoring Blood Glucose (SMBG)
7 secondary outcomes
Glycemic efficacy: Occurrence of hypoglycemia
Time frame: 24 weeks
Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism
Time frame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period
Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism, Laboratory tests evaluated for significant changes from baseline by treated groups
Time frame: Time Frame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period
Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG)
Time frame: 24 weeks
Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG) Weekly Assessment
Time frame: 24 weeks
Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Daily Assessment
Time frame: 24 weeks
Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Overnight Assessment
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gopal Saha, MD study director
Rezolute
18 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RZ358 (5-10 mg/kg) + SOC in people with Congenital Hyperinsulinism, run by Rezolute at 18 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, France, Germany, Spain, United Kingdom and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glycemic efficacy: Target glucose control (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.