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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04538989
Recruitment Status : Recruiting
First Posted : September 4, 2020
Last Update Posted : October 20, 2020
Sponsor:
Information provided by (Responsible Party):
Rezolute

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).

Condition or disease Intervention/treatment Phase
Congenital Hyperinsulinism Drug: RZ358 Sequential Group Cohort 1 Drug: RZ358 Sequential Group Cohort 2 Drug: RZ358 Sequential Group Cohort 3 Drug: RZ358 Sequential Group Cohort 4 Phase 2

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 4 weeks will evaluate eligibility. Once enrolled, RZ358 will be administered weekly for the first month and then bi-weekly for the second month for a total treatment period of 8 weeks and a post-treatment follow-up period of 15 weeks.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Multiple-Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
Estimated Study Start Date : October 2020
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: RZ358 Cohort 1 Drug: RZ358 Sequential Group Cohort 1
IV infusion for 8 weeks (3 mg/kg weekly for 4 weeks followed by 3 mg/kg bi-weekly for 4 weeks)

Experimental: RZ358 Cohort 2 Drug: RZ358 Sequential Group Cohort 2
IV infusion for 8 weeks (6 mg/kg weekly for 4 weeks followed by 6 mg/kg bi-weekly for 4 weeks)

Experimental: RZ358 Cohort 3 Drug: RZ358 Sequential Group Cohort 3
IV infusion for 8 weeks (9 mg/kg weekly for 4 weeks followed by 9 mg/kg bi-weekly for 4 weeks)

Experimental: RZ358 Cohort 4 Drug: RZ358 Sequential Group Cohort 4
IV infusion for 8 weeks (fixed weekly titration from 3 to 12 mg/kg for 4 weeks, followed by 9 mg/kg bi-weekly for 4 weeks)




Primary Outcome Measures :
  1. Glycemic efficacy: Target glucose control [ Time Frame: 8 weeks ]
    Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)

  2. Glycemic efficacy: Target glucose control [ Time Frame: 4 weeks ]
    Change from Baseline in Percent Time in Glucose Target Range by Continuous Glucose Monitor (CGM)

  3. 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.

  4. 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).


Secondary Outcome Measures :
  1. Glycemic efficacy: Occurrence of hypoglycemia [ Time Frame: 8 weeks ]
    Change from Baseline in the Incidence of Hypoglycemia by Self-Monitored Blood Glucose (SMBG)

  2. Glycemic efficacy: Duration of Hypoglycemia [ Time Frame: 8 weeks ]
    Change from Baseline in the Absolute (minutes) and Percent Time with Hypoglycemia by CGM

  3. Glycemic efficacy: Occurrence of Hypoglycemia [ Time Frame: 8 weeks ]
    Change from Baseline in the Incidence of Hypoglycemia by CGM

  4. 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

  5. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female age 12-45 years old 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04538989


Contacts
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Contact: Malathi Robaina 650-206-4507 clinicaltrials@rezolutebio.com
Contact: Brian Roberts, M.D. brian@rezolutebio.com

Locations
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United States, Texas
Cook Children's Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Principal Investigator: Paul Thornton, MD         
Bulgaria
SHAT Children diseases "Prof. Dr. Ivan Mitov" Recruiting
Sofia, Bulgaria
Principal Investigator: Radka Savova, MD         
Denmark
Odense University Hospital Recruiting
Odense, Denmark, 5000
Principal Investigator: Henrik Christesen, MD         
Georgia
LTD "Pediatric Surgery Centre" Recruiting
Tbilisi, Georgia, 0122
Principal Investigator: Nino Kheladze, MD         
Germany
Magdeburg University Clinic Center (Otto-von-Guericke Universität) Recruiting
Magdeburg, Germany, 39120
Principal Investigator: Klaus Mohnike, MD         
Spain
Hospital Universitari Vall d' Hebron Recruiting
Barcelona, Spain, 08035
Principal Investigator: María Clemente, MD         
Sponsors and Collaborators
Rezolute
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Responsible Party: Rezolute
ClinicalTrials.gov Identifier: NCT04538989    
Other Study ID Numbers: RZ358-606-US
First Posted: September 4, 2020    Key Record Dates
Last Update Posted: October 20, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rezolute:
Hypoglycemia
Congenital Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Hyperinsulinism
Additional relevant MeSH terms:
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Congenital Hyperinsulinism
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Infant, Newborn, Diseases
Hypoglycemia