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Completed

NCT Number: NCT04538989

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

The objective of this trial is to evaluate the safety, tolerability and glucose-raising effects of RZ358 in patients with Congenital Hyperinsulinism (HI).

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Key information

Conditions

Congenital Hyperinsulinism Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Glucose Metabolism Disorders Hyperinsulinism Hypoglycemia Infant, Newborn, Diseases Metabolic Diseases Nutritional and Metabolic Diseases Pancreatic Diseases

Age range

2 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

SHAT Children diseases "Prof. Dr. Ivan Mitov", Sofia, Bulgaria

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About this study

There is a significant unmet medical need to develop new therapies aimed at preventing chronic recurrent hypoglycemia in congenital HI, the most common cause of persistent hypoglycemia in children. RZ358 is a human mAb that allosterically attenuates excessive insulin action on target cells. Therefore, RZ358 is ideally suited as a potential therapy for hyperinsulinism, and it is being developed to treat the hypoglycemia associated with diseases such as congenital HI. This is a Phase 2, multicenter, open label clinical study designed to assess the safety and efficacy of four progressively higher doses of RZ358 in separate groups of patients with hyperinsulinemic hypoglycemia due to Congenital HI, not adequately controlled with or without current standard of care. A screening period of up to 5 weeks will evaluate eligibility. Once enrolled, RZ358 will be administered bi-weekly over 8 weeks, and then patients will complete a post-treatment follow-up period of 13 weeks.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

RZ358 Sequential Group Cohort 1

Drug

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

RZ358 Sequential Group Cohort 2

Drug

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

RZ358 Sequential Group Cohort 3

Drug

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

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)

Primary outcomes

  1. 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)

    Time frame: 8 weeks

    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.

  2. 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)

    Time frame: 8 weeks

    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.

  3. Repeat Dose Pharmacokinetics of RZ358

    Time frame: 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

    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.

Secondary outcomes

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

    Time frame: 8 weeks

    The median of average weekly number of overall hypoglycemia events (<70 mg/dL [3.9mmol/L], moderate hypoglycemia events (<60 mg/dL [3.3 mmol/L] and severe hypoglycemia events (<50 mg/dL [2.8mmol/L]) by SMBG at baseline (BL) and end of treatment (EOT) is reported.

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

    Time frame: 8 weeks

    The average weekly number overall hypoglycemia events (<70 mg/dL [3.9mmol/L], moderate hypoglycemia events (<60 mg/dL [3.3 mmol/L] and severe hypoglycemia events (<50 mg/dL [2.8mmol/L]) by SMBG is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

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

    Time frame: 8 weeks

    The median of average daily percent time in overall (<70 mg/dL [<3.9 mmol/L]), moderate (<60 mg/dL [3.3 mmol/L]), and severe (<50 mg/dL [2.8 mmol/L]) hypoglycemia at baseline (BL) and end of treatment (EOT) is reported.

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

    Time frame: 8 weeks

    The average daily percent time in overall (<70 mg/dL [<3.9 mmol/L]), moderate (<60 mg/dL [3.3 mmol/L]), and severe (<50 mg/dL [2.8 mmol/L]) hypoglycemia is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

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

    Time frame: 8 weeks

    The median of average duration (minutes) in overall (<70 mg/dL [<3.9 mmol/L]), moderate (<60 mg/dL [3.3 mmol/L] ), and severe (<50 mg/dL [2.8 mmol/L]) hypoglycemia by CGM at baseline (BL) and end of treatment (EOT) is reported.

  6. Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)

    Time frame: 8 weeks

    The average duration (minutes) in overall (<70 mg/dL [<3.9 mmol/L]), moderate (<60 mg/dL [3.3 mmol/L] ), and severe (<50 mg/dL [2.8 mmol/L]) hypoglycemia by CGM is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

  7. Occurrence of Hypoglycemia During Fasting Challenge

    Time frame: 8 Weeks

    The occurrence of hypoglycemia during a 12 Hour fasting challenge.

  8. Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)

    Time frame: 8 weeks

    The median of average hypoglycemia events per day at each of the specified glucose thresholds [<70, <60, and <50 mg/dL (3.9, 3.3, and 2.8 mmol/L)], by CGM at baseline (BL) and end of treatment (EOT) is reported.

  9. Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)

    Time frame: 8 weeks

    The average hypoglycemia events per day at each of the specified glucose thresholds [<70, <60, and <50 mg/dL (3.9, 3.3, and 2.8 mmol/L)], by CGM is compared from baseline (BL) to end of treatment (EOT) and the median net changes of those differences are reported.

  10. Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)

    Time frame: 8 weeks

    The median of average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) at baseline (BL) and end of treatment (EOT) is reported.

  11. Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)

    Time frame: 8 weeks

    The average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) is compared from baseline (BL) to end of treeatment (EOT) and the median percent change of that difference is reported.

Sponsors and collaborators

Lead sponsor

Rezolute

Other

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Sep 4, 2020
Registry last updated
May 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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