Clinical Trials Register

Summary
EudraCT Number:	2016-004186-83
Sponsor's Protocol Code Number:	RZ358-606
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-01-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2016-004186-83

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A non-blinded study of multiple doses of RZ358, in patients with low blood sugars due to genetic dysfunction resulting in over-secretion of insulin

A.4.1

Sponsor's protocol code number

RZ358-606

A.5.4

Other Identifiers

Name:

IND Number

Number:

119319

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Rezolute, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Rezolute, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Rezolute, Inc
B.5.2	Functional name of contact point	Clinical Trials Info
B.5.3	Address:
B.5.3.1	Street Address	201 Redwood Shores Parkway, Suite 315
B.5.3.2	Town/ city	Redwood City
B.5.3.3	Post code	CA 94065
B.5.3.4	Country	United States
B.5.4	Telephone number	+1650206-4507
B.5.6	E-mail	info@rezolutebio.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/040/16
D.3 Description of the IMP
D.3.2	Product code	RZ358
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not Available
D.3.9.2	Current sponsor code	RZ358
D.3.9.3	Other descriptive name	fully human IgG2 monoclonal antibody
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hypoglycemia associated with congenital hyperinsulinism

E.1.1.1

Medical condition in easily understood language

Low blood glucose levels associated with abnormally high level of insulin due to a specific birth defect

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10077227
E.1.2	Term	Hyperinsulinemic hypoglycemia
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10020644
E.1.2	Term	Hyperinsulinism NOS
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10061211
E.1.2	Term	Hyperinsulinism
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10022484
E.1.2	Term	Insulin hypoglycaemia
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objectives of this study are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and glycemic efficacy of multiple ascending doses of RZ358 over 8 weeks in patients with hyperinsulinemic hypoglycemia due to congenital hyperinsulinism (CHI).

E.2.2

Secondary objectives of the trial

not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provide written informed consent and, as applicable, assent, before any study specific procedures are performed
2. At Screening, aged ≥2 years and ≤45 years
3. An established clinical diagnosis, with or without a genetic diagnosis, of congenital hyperinsulinism
4. Patient is currently receiving SOC medications (i.e corticosteroids, diazoxide, lanreotide, sirolimus, and octreotide) and/or nutritional supplementation for CHI, with at least 2 months of stable treatment; OR is not on treatment, at the time of Screening.
5. Glucose values <70 mg/dL (3.9 mmol/L) for ≥4% of the overall monitored CGM time with at least 3 severe hypoglycemia events by CGM threshold of <50mg/dL (2.8mmol/L) during the last 7 days of a 10-day Screening CGM evaluation period;
A discrete severe hypoglycemia event by CGM is defined by having at least 3 consecutive (15 monitored minutes) hypoglycemia readings <70 mg/dL (3.9 mmol/L) with at least one of those readings <50 mg/dL (2.8 mmol/L) and with at least 60 monitored minutes of glucose values ≥ 70 mg/dL (3.9 mmol/L) in between events.
AND
Experiencing ≥ 3 hypoglycemia events (<70 mg/dL) per week by SMBG and/or according to the Investigator’s evaluation.
6. Hepatic ultrasound at Screening without clinically significant findings, including clinically significant gallstones as judged by the Investigator (e.g. large size, obstructive, biliary colic, or LFT abnormalities exceeding protocol thresholds) or evidence of peliosis hepatitis
7. For female patients of childbearing potential, a negative serum or urine pregnancy test within 7 days before dosing Females of childbearing potential are defined as fertile following menarche and until becoming postmenopausal or permanently sterile. Note: Postmenopausal is defined as absence of vaginal bleeding or spotting for at least 1 year. Permanently sterile is defined as having had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
8. For female patients of childbearing potential, a willingness to use highly effective* contraceptive measures adequate to prevent a new pregnancy for the duration of the study, including for at least 105 days after receiving the last dose of study drug. For women with reproductive potential who use a hormonal method of contraception, concurrent use of a second (barrier) method is recommended. (*Highly effective methods of birth control are defined as those that result in a low failure rate [ie, less than 1% per year] when used consistently and correctly [eg, implants, injectables, oral contraceptives, some intrauterine devices, bilateral tubal occlusion, true sexual abstinence in line with the preferred and usual lifestyle of the patient, or vasectomized partner.])
9. For sexually active males, a willingness to use contraceptive measures, e.g. a condom, for the duration of the study, including for at least 105 days after receiving the last dose of study drug. In addition, males must agree not to donate sperm over the same study period.

E.4

Principal exclusion criteria

1. Any out-of-range laboratory value at Screening that has not been reviewed, approved, and documented as not clinically significant by the Investigator, with the exception of liver function tests for total bilirubin, ALT, AST, and ALP, which must be within 1.5X the upper limit of normal (ULN) for the reference range
2. Body mass index ≥ 35 kg/m2 for patients aged 18 years and above, or BMI ≥99% (percentile) per CDC growth charts for patients >12 and < 18 years of age.
3. History of malignancy within 3 years before Screening other than carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell carcinoma of the skin
4. History of seropositivity for HIV antibody, hepatitis B, or hepatitis C antibody
5. Major general surgery within 3 months before Screening or anticipated during the study period
6. Use of systemic corticosteroids within 30 days before Screening
7. Known allergy or sensitivity to RZ358 or any component of the study drug
8. Treatment with an investigational drug or device within 30 days or 5 half-lives of the investigational drug before Day 1 of Week 1, whichever is longer. Participation in registries and purely diagnostic studies is allowed.
9. Female patients who are pregnant, planning to become pregnant during the course of the study, have recently delivered (within 3 months before Screening), or are breastfeeding
10. Male patients who are planning a pregnancy with a female partner during the course of the study or within 105 days after administration of study drug
11. Any organ condition, concomitant disease (eg, psychiatric illness, severe alcoholism, or drug abuse, cardiac, hepatic, or kidney disease), or other abnormality that itself, or the treatment of which, could interfere with the conduct of the study (eg, may affect absorption, distribution, metabolism, or elimination of the study drug) or that, in the opinion of the Investigator and/or Sponsor’s medical monitor, would pose an unacceptable risk to the patient in the study.

E.5 End points

E.5.1

Primary end point(s)

• Glycemic efficacy of RZ358 as evaluated by the average daily percent time within a glucose target range of 70-180 mg/dL (3.9-10 mmol/L) by continuous glucose monitoring (CGM);
• Repeat-dose safety and tolerability of RZ358
• Repeat-dose pharmacokinetics of RZ358.

E.5.1.1

Timepoint(s) of evaluation of this end point

Measured at various timepoints (see schedule of events)

E.5.2

Secondary end point(s)

• Average weekly incidence of hypoglycemia (< 70 mg/dL) by self-monitored blood glucose (SMBG)
• Average daily duration and percent time with hypoglycemia at thresholds of:
< 70 mg/dL (3.9 mmol/L)
< 60 mg/dL (3.3 mmol/L)
< 50 mg/dL (2.8 mmol/L)
by continuous glucose monitoring (CGM)

• Average daily hypoglycemia incidence (event rate) at each of the specified glucose thresholds by CGM;
• Average 8h overnight percent time in glucose target range of 70-180 mg/dL (3.9-10 mmol/L) by CGM;
• Occurrence of hypoglycemia during a 12h fasting challenge

E.5.2.1

Timepoint(s) of evaluation of this end point

Measured at various timepoints (see schedule of events)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Georgia

Israel

Russian Federation

Serbia

Turkey

United States

Bulgaria

Denmark

Germany

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minors will be included in this study. They will be given age appropriate information sheets and assent will be collected alongside parental/legal guardian consent where appropriate.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the conclusion of the study, patients should be treated with SOC, as appropriate. At the discretion of the Sponsor and Investigator, patients perceived to benefit from RZ358 on the present trial may be eligible for continued treatment with RZ358 under an expanded access/extension program, which is intended to be available once RZ358 enters Phase 3 development, as applicable and appropriate.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-06-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-30

P. End of Trial
P.	End of Trial Status	Ongoing

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