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

• ClinicalTrials.gov Identifier: NCT04538989
• Recruitment Status: Completed
• First Posted: September 4, 2020
• Last Update Posted: September 8, 2022
• Sponsor: Rezolute
• Information provided by (Responsible Party): Rezolute

Tracking Information

• First Submitted Date: August 21, 2020
• First Posted Date: September 4, 2020
• Last Update Posted Date: September 8, 2022
• Actual Study Start Date: February 24, 2020
• Actual Primary Completion Date: April 5, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 15, 2021)

• Glycemic efficacy: Target glucose control [ Time Frame: 8 weeks ]
  Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)
• Repeat dose safety and tolerability of RZ358 [ Time Frame: Through 21 Weeks ]
  Occurrence of a safety signal as assessed by the incidence of treatment-emergent AEs, SAEs, and AEs leading to study drug discontinuation.
• Repeat dose pharmacokinetics of RZ358 [ Time Frame: Through 8 weeks ]
  Change from baseline in RZ358 drug exposure as assessed by Population-PK modeling of maximum concentrations (Cmax) and Area under the Concentration-Time Curve (AUC).

Original Primary Outcome Measures (submitted: August 31, 2020)

• Glycemic efficacy: Target glucose control [ Time Frame: 8 weeks ]
  Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)
• Glycemic efficacy: Target glucose control [ Time Frame: 4 weeks ]
  Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)
• Repeat dose safety and tolerability of RZ358 [ Time Frame: Through 27 Weeks ]
  Occurrence of a safety signal as assessed by the incidence of treatment-emergent AEs, SAEs, and AEs leading to study drug discontinuation.
• Repeat dose pharmacokinetics of RZ358 [ Time Frame: Through 8 weeks ]
  Change from baseline in RZ358 drug exposure as assessed by Population-PK modeling of maximum concentrations (Cmax) and Area under the Concentration-Time Curve (AUC).

Current Secondary Outcome Measures (submitted: August 31, 2020)

• Glycemic efficacy: Occurrence of hypoglycemia [ Time Frame: 8 weeks ]
  Change from Baseline in the Incidence of Hypoglycemia by Self-Monitored Blood Glucose (SMBG)
• Glycemic efficacy: Duration of Hypoglycemia [ Time Frame: 8 weeks ]
  Change from Baseline in the Absolute (minutes) and Percent Time with Hypoglycemia by CGM
• Glycemic efficacy: Occurrence of Hypoglycemia [ Time Frame: 8 weeks ]
  Change from Baseline in the Incidence of Hypoglycemia by CGM
• Overnight Target Glucose Control [ Time Frame: 8 weeks ]
  Change from Baseline in Percent Time in Overnight (midnight to 8 am) Glucose Target Range by CGM
• Glycemic Efficacy: Ability to Complete a Fast without Hypoglycemia [ Time Frame: 8 weeks ]
  Change from Baseline in Incidence of Hypoglycemia by SMBG, During a 12-hour Fasting Challenge

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
• Official Title: An Open-Label Multiple-Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
• Brief Summary: The objective of this trial is to evaluate the safety, tolerability and glucose-raising effects of RZ358 in patients with Congenital Hyperinsulinism (HI).
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Congenital Hyperinsulinism

Intervention

• Drug: RZ358 Sequential Group Cohort 1
  IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)
• Drug: RZ358 Sequential Group Cohort 2
  IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)
• Drug: RZ358 Sequential Group Cohort 3
  IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
• Drug: RZ358 Sequential Group Cohort 4
  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)

Study Arms

• Experimental: RZ358 Cohort 1
  Intervention: Drug: RZ358 Sequential Group Cohort 1
• Experimental: RZ358 Cohort 2
  Intervention: Drug: RZ358 Sequential Group Cohort 2
• Experimental: RZ358 Cohort 3
  Intervention: Drug: RZ358 Sequential Group Cohort 3
• Experimental: RZ358 Cohort 4
  Intervention: Drug: RZ358 Sequential Group Cohort 4

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 7, 2022): 23
• Original Estimated Enrollment (submitted: August 31, 2020): 32
• Actual Study Completion Date: August 19, 2022
• Actual Primary Completion Date: April 5, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 45 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Denmark, Georgia, Germany, Israel, Russian Federation, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT04538989
• Other Study ID Numbers: RZ358-606
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Rezolute
• Original Responsible Party: Same as current
• Current Study Sponsor: Rezolute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Rezolute
• Verification Date: June 2021