Clinical Trials Register

Summary
EudraCT Number:	2013-002249-13
Sponsor's Protocol Code Number:	TN-18
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-07-15
Trial 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2013-002249-13

A.3

Full title of the trial

CTLA-4Ig (Abatacept) for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus

A.3.1

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

Preventing Abnormal Glucose Tolerance and Diabetes with an Antibody in Relatives at Risk for the Disease

A.4.1

Sponsor's protocol code number

TN-18

A.5.4

Other Identifiers

Name:

IND

Number:

117,208

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	TrialNet Coordinating Center
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK)
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Juvenile Diabetes Research Foundation (JDRF)
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	TrialNet Coordinating Center
B.5.2	Functional name of contact point	Amanda Terry
B.5.3	Address:
B.5.3.1	Street Address	Pediatrics Epidemiology Center at the University of
B.5.3.2	Town/ city	Tampa, Florida
B.5.3.3	Post code	33612
B.5.3.4	Country	United States
B.5.4	Telephone number	1813396 9429
B.5.5	Fax number	1 813910 1234
B.5.6	E-mail	amanda.terry@epi.usf.edu

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	Yes
D.2.1.1.1	Trade name	Abatacept (Orencia)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharmaceutical Research Institute
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CTLA-4 Ig
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

A soluble fusion protein, CTLA-4 Ig, is to be used for the prevention of
abnormal glucose tolerance and diabetes in relatives at risk of
developing the disease.

E.1.1.1

Medical condition in easily understood language

High blood sugar and Type 1 Diabetes

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10066284
E.1.2	Term	Diabetes prophylaxis
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to determine whether treatment of
subjects at risk for diabetes with Abatacept results in delay or
prevention of abnormal glucose tolerance.

E.2.2

Secondary objectives of the trial

Secondary objectives will determine whether treatment with Abatacept
is superior to placebo with respect to the incidence of Type 1 Diabetes
Mellitus, determine whether treatment with Abatacept is superior to
placebo with respect to C peptide responses to oral glucose, as obtained
from timed collections during longitudinal tests, to compare the safety
and tolerability of Abatacept to placebo, and to assess the effects of
treatment on mechanistic outcomes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Study subjects must be or have:
1. Participant in TrialNet Natural History/Pathway to Prevention Study
(TN01) and thus, a relative of a proband with T1DM.
2. Between the ages of 1-45 years at the time of enrollment in TN01 and
age ≥ 6 at time of randomization in this trial.
3. Willing to provide Informed Consent or have a parent or legal
guardian provide informed consent the subject is <18 years of age.
4. Normal glucose tolerance by OGTT within 7 weeks (no more than 52
days) of baseline (visit 0). If previous abnormal glucose tolerance, has had two consecutive OGTTs with normal glucose tolerance.
a. Fasting plasma glucose < 110 mg/dL (6.1 mmol/L), and
b. 2 hour plasma glucose <140 mg/dL (7.8 mmol/L), and
c. 30, 60, or 90 minute value on OGTT< 200mg/dL (11.1 mmol/L)
5. At least two diabetes-related autoantibodies confirmed to be present on two occasions, not including mIAA. Confirmation of 2 positive autoantibodies must occur within the six months prior to randomization, but the confirmation does not have to involve the same 2 autoantibodies.
6. Weight ≥ 20 kg at Baseline Visit.
7. If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to each infusion.
8. At least three months from date of last live immunization.
9. Willing to forgo live vaccines while receiving treatment on study and for three months following last study drug administration.
had two consecutive OGTTs with normal glucose tolerance.

E.4

Principal exclusion criteria

Potential participants must not meet any of the following exclusion
criteria:
1. Abnormal Glucose Tolerance or Diabetes
a. Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L), or
b. 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or
c. 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1
mmol/L)
2. Insulin autoantibodies (mIAA).
3. Immunodeficient or have clinically significant chronic lymphopenia.
4. Have an active infection at time of randomization.
5. Have a positive PPD test result or history of previously treated TB, or
positive interferongamma release assay (IGRA) test.
6. Be currently pregnant or lactating, or anticipate getting pregnant
within 3 months of the last study drug administration.
7. Use of medications known to influence glucose tolerance.
8. Require use of other immunosuppressive agents.
9. Have serologic evidence of current or past HIV, Hepatitis B (positive
for Hepatitis B core
antibody or surface antigen), or Hepatitis C infection.
10. Have serological evidence of current CMV infection.
11. Have evidence of active EBV infection.
12. Have any complicating medical issues or abnormal clinical laboratory
results that interfere with study conduct or cause increased risk. These
include pre-existing cardiac disease, COPD, neurological, or blood count
abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia).
13. Have a history of malignancies.
14. Have Multiple Sclerosis

E.5 End points

E.5.1

Primary end point(s)

The elapsed time from treatment randomisation to the development of
abnormal glucose tolerance.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 Years

E.5.2

Secondary end point(s)

The elapsed time from the development of abnormal glucose tolerance to
the development of type 1 diabetes.

E.5.2.1

Timepoint(s) of evaluation of this end point

6 years

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

Australia

Finland

Germany

Italy

New Zealand

Sweden

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

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

If the accrual rate is 50 patients per year, with the above assumptions
it is estimated that the enrollment period will last
approximately 4 years and a study duration of approximately 6 years
will provide a sufficient number of events to detect the assumed
treatment difference. Participants who develop AGT will remain on
study and be followed according to protocol to assess the secondary
objective of time until T1DM development.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1