Clinical Trials Register

Summary
EudraCT Number:	2015-002847-32
Sponsor's Protocol Code Number:	X358602
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-08-24
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

UK - MHRA

A.2

EudraCT number

2015-002847-32

A.3

Full title of the trial

A Single-Dose Open-Label Study of XOMA 358 in Subjects with Congenital Hyperinsulinism (HI)

A.3.1

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

A single-dose study of a new biologic drug for people with abnormal levels of insulin due to a genetic dysfunction

A.4.1

Sponsor's protocol code number

X358602

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	XOMA (US) LLC
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	XOMA (US) LLC
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	Clinical Networks Services (UK) Ltd
B.5.2	Functional name of contact point	BioDesk
B.5.3	Address:
B.5.3.1	Street Address	Fountain Court, 2 Victoria Square, Victoria Street
B.5.3.2	Town/ city	St. Albans
B.5.3.3	Post code	AL1 3TF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441727884612
B.5.6	E-mail	yadvinder.gill@clinical.net.au

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.3.1	Product name	XOMA 358
D.3.2	Product code	XOMA 358
D.3.4	Pharmaceutical form	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	imunoglobulin G 2 (IgG2)
D.3.9.2	Current sponsor code	XOMA 358
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	20
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

Hypoglycaemia associated with congenital hyperinsulinism

E.1.1.1

Medical condition in easily understood language

Low glucose 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	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10020644
E.1.2	Term	Hyperinsulinism NOS
E.1.2	System Organ Class	100000004861

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10022484
E.1.2	Term	Insulin hypoglycaemia
E.1.2	System Organ Class	100000004861

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

To evaluate the safety and clinical pharmacology of a single dose of XOMA 358 in subjects with hypoglycaemia associated with congenital hyperinsulinism.

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. Aged at least 12 years at Screening
3. An established clinical diagnosis, with or without a genetic diagnosis, of congenital hyperinsulinism
4. Duration of glucose levels < 70 mg/dL, by CGM, for an average of at least
120 minutes across baseline Days -3, -2, and -1 with no single duration < 60 minutes on any of the baseline Days -3, -2, or -1, unless the subject received rescue treatment
5. In the opinion of the Investigator, can be safely washed out of background HI medications
6. Hepatic ultrasound at Screening without clinically significant findings or evidence of peliosis hepatis
7. For female subjects of childbearing potential, a negative serum pregnancy test
8. For females subjects of childbearing potential and male subjects with a female partner of childbearing potential, a willingness to use contraceptive measures adequate to prevent the subject or subject’s partner from becoming pregnant during the study and for at least 4 months after the administration of study drug.

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 (UNL) for the reference range
2. During confinement, use of any agent, such as diazoxide, octreotide, chronic systemic glucocorticoids, or β agonists, that may affect glucose metabolism. Such agents will be washed out after checking-in to the in-patient research facility and before dosing. Topical, inhaled, and intranasal corticosteroids at doses that are unlikely to affect glucose homeostasis and corticosteroids for ophthalmic use are permitted.
3. Body Mass Index ≥ 35 kg/m2
4. History of malignancy within 3 years before Screening other than carcinoma in situ of the cervix or adequately treated nonmetastatic squamous or basal cell carcinoma of the skin
5. History of seropositivity for HIV antibody, hepatitis B, or hepatitis C antibody
6. Major general surgery within 3 months before Screening or anticipated during the study period
7. Known allergy or sensitivity to XOMA 358 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, whichever is longer. Participation in registries and purely diagnostic studies is allowed.
9. Female subjects who are pregnant, planning to become pregnant during the course of the study, have recently delivered (within 3 months before Screening), or are breast- feeding
10. Male subjects who are planning a pregnancy with a female partner during the course of the study or within 4 months 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 subject in the study.

E.5 End points

E.5.1

Primary end point(s)

Effect on Glucose (Glucose AUC24, average time per day of blood glucose < 70 mg/dL)

E.5.1.1

Timepoint(s) of evaluation of this end point

Measured at various time points (see schedule of events)

E.5.2

Secondary end point(s)

Number of hypoglycemic events per day with glucose < 70 mg/dL, <60 mg/dL, and <50 mg/dL
Fasting and postprandial glucose, insulin, C-peptide, ketones, free fatty acids;
Time to hypoglycaemia;
Frequency of hypoglycemia events (<60 mg/dL)
Concomitant treatment/medications used during rescue

E.5.2.1

Timepoint(s) of evaluation of this end point

Measured at various time points (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

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

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.8.2.4

Number of treatment arms in the trial

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

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

United States

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1