RZ358 for Congenital Hyperinsulinism

(sunRIZE Trial)

Recruiting at 26 trial locations

Overseen By Gopal Saha, MD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Rezolute

Must be taking: Standard of care

Disqualifiers: Diabetes, Pre-diabetes, High BMI, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RZ358 for individuals with congenital hyperinsulinism (HI), a condition where the body produces excessive insulin, leading to low blood sugar. The research aims to evaluate the effectiveness and safety of RZ358 when combined with standard treatments. Participants will receive either RZ358 with their usual treatment or a placebo (a harmless pill with no effect) to compare outcomes. Those who frequently experience low blood sugar episodes each week, despite current treatment, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. It mentions that RZ358 is added to standard-of-care treatments, so you may continue your existing medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RZ358, also known as ersodetug, has been safe and well-tolerated in past studies. These studies found that patients with congenital hyperinsulinism (HI) who took RZ358 experienced fewer episodes of low blood sugar. RZ358 increased blood sugar levels without causing significant side effects.

The doses used in current trials have demonstrated similar safety results. Participants handled the treatment well, with no major side effects reported. This suggests that RZ358 could be a promising option for managing HI when used alongside standard care. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hyperinsulinism?

Unlike the standard treatments for congenital hyperinsulinism, which often include medications like diazoxide, octreotide, or even surgical interventions, RZ358 offers a novel approach. RZ358 is unique because it targets the insulin receptor directly, helping to control blood sugar levels by counteracting excessive insulin. Researchers are excited about RZ358 because it has the potential to be more effective and specific than current treatments, possibly leading to better management of blood glucose with fewer side effects. This could be a game-changer for patients, especially younger ones, who struggle with the limitations of existing therapies.

What evidence suggests that this trial's treatments could be effective for congenital hyperinsulinism?

Research has shown that RZ358 (ersodetug) could help treat congenital hyperinsulinism (HI). In earlier studies, RZ358 significantly reduced the frequency and duration of low blood sugar events. It achieves this by affecting the insulin receptor, which plays a crucial role in controlling blood sugar levels. Notably, RZ358 might treat HI regardless of its cause, due to its role in the body's metabolic process. Early results also suggest that RZ358 is generally safe and well-tolerated by patients. Participants in this trial may receive RZ358 at different dosages or a placebo, alongside standard-of-care therapy, to further evaluate its effectiveness and safety. ^{1 3 6 7 8}

Who Is on the Research Team?

Gopal Saha, MD

Principal Investigator

Rezolute

Are You a Good Fit for This Trial?

This trial is for individuals with congenital hyperinsulinism, a condition causing excessive insulin production. Participants should be currently receiving standard treatments without sufficient control of their condition.

Inclusion Criteria

I am between 3 months and 45 years old.

I have been diagnosed with congenital hyperinsulinism, with or without a known genetic cause.

I have low blood sugar levels 3 or more times a week.

Exclusion Criteria

I am allergic to RZ358 or its ingredients.

My BMI is 35 or higher, or I am a teen with a BMI in the top 1% for my age.

My blood sugar is often high, more than 5% of the time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RZ358 or placebo as add-on to standard-of-care therapy for congenital hyperinsulinism

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of RZ358 treatment long-term

Up to two years

What Are the Treatments Tested in This Trial?

Interventions

• RZ358 Treatment

Trial Overview The study tests RZ358 at different doses (5 mg/kg and 10 mg/kg) added to the usual care versus a placebo plus usual care over six months. It also looks at how safe and effective RZ358 is over a longer period.

How Is the Trial Designed?

Group I: Open Label Arm, SoC + RZ358 (start 5mg/kg and increase to 10 mg/kg per protocol schedule Experimental Treatment 1 Intervention

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

Group II: SoC (Standard-of-Care) + RZ358 (5 mg/kg) or Placebo Placebo Group 1 Intervention

Participants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo

Group III: SoC + RZ358 (10 mg/kg) or Placebo Placebo Group 1 Intervention

Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo

Who Is Running the Clinical Trial?

Rezolute

Lead Sponsor

Trials

4

Recruited

230+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666634025000388

Global, multi-center, repeat-dose, phase 2 study of RZ358 ... Ersodetug, a monoclonal antibody targeting the insulin receptor, was able to significantly reduce hypoglycemia events and duration.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06208215?cond=Congenital%20Hyperinsulinism&viewType=Table&rank=2

RZ358 Treatment for 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- ...

3. rezolutebio.com rezolutebio.com/pipeline/

Pipeline At doses and exposures that are planned for sunRIZE, RZ358 (ersodetug) was generally safe and well-tolerated, and resulted in median improvements in ...

4. horizonscandb.pcori.org horizonscandb.pcori.org/report/topics/822

Ersodetug (RZ358) to treat congenital hyperinsulinism Because ersodetug acts downstream from beta cells in the metabolic pathway, it might be universally effective for treating congenital hyperinsulinism regardless ...

5. cell.com cell.com/med/pdf/S2666-6340(25)00038-8.pdf

Global, multi-center, repeat-dose, phase 2 study of RZ358 ( ... Congenital hyperinsulinism is associated with poor neurologic outcomes, with limited therapeutic advancements in nearly half a century.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04538989

An Open-Label Multiple Dose Study of RZ358 in Patients ... The objective of this trial is to evaluate the safety, tolerability and glucose-raising effects of RZ358 in patients with Congenital Hyperinsulinism (HI).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06208215?term=AREA%5BConditionSearch%5D(Familial%20hyperinsulinism)&rank=6

RZ358 Treatment for 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 ...

8. rezolutebio.com rezolutebio.com/publications/data-presentations/

Data Presentations Single-Dose-Studies-of-RZ358-in-Patients-with-. Single Dose Studies of RZ358 in Patients with Congenital Hyperinsulinism: Results of Population PK/PD ...