Clinical Trials Register

Summary
EudraCT Number:	2019-003265-17
Sponsor's Protocol Code Number:	S63466
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-01-07
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

Denmark - DHMA

A.2

EudraCT number

2019-003265-17

A.3

Full title of the trial

Phase II, dose ranging, efficacy study of anti-thymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes (T1D)

A.3.1

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

Phase II, dose ranging, efficacy study of anti-thymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes (T1D)

A.4.1

Sponsor's protocol code number

S63466

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	Universitair Ziekenhuis Leuven, Belgium
B.1.3.4	Country	Belgium
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	Universitair Ziekenhuis Leuven, Belgium
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universitair Ziekenhuis Leuven, Belgium
B.5.2	Functional name of contact point	Professor Chantal Mathieu
B.5.3	Address:
B.5.3.1	Street Address	Herestraat 49, O&N1, bus 902
B.5.3.2	Town/ city	Leuven
B.5.3.3	Post code	B-3000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003216342129

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.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Anti-human thymocyte globulin (rabbit)
D.3.2	Product code	08854
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	Yes
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)	No
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	Solvent for parenteral use
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

Type 1 diabetes (T1D)

E.1.1.1

Medical condition in easily understood language

Type 1 diabetes

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective:
To determine the changes in stimulated C-peptide response over the first two hours of a mixed meal tolerance test (MMTT) at 12 months for 2.5mg/kg ATG arm versus the placebo.
• Conditional on finding a statistical difference between the 2.5mg/kg ATG arm and placebo, to identify the minimally effective dose (lowest dose significantly different to placebo) amongst the doses studied in the trial using change in stimulated C-peptide response over the first two hours of a MMTT at 12 months versus placebo.

E.2.2

Secondary objectives of the trial

Secondary objective
• To determine the effects of ATG treatment on:
o MMTT-stimulated C-peptide (at baseline, 3, 6 and 12 months)
o HbA1c and total daily insulin dose (units/kg) (at baseline, 3, 6, 12 months)
o Fasting/stimulated dried blood spot (DBS) C-peptide measurements (monthly)
o CGM measures over 14 days at 3, 6 and 12 months
• To determine whether ATG treatment mediates a reduction in CD4 positive T-cells but relative preservation of CD8 positive T-cells
• Descriptive analysis of the safety profile of different doses of ATG in different age groups

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria:
1. Has given written informed consent to participate; or have a parent or legal guardian provide written informed consent. Individual under the age of consent will be asked to assent to trial participation.
2. Be aged ≥5 years to ≤25 years at written informed consent/assent
3. Have been diagnosed with T1D within 3–9 weeks of planned treatment day 1
4. Have random C-peptide levels ≥200 pmol/L measured at screening, as tested centrally
5. Have 1 or more diabetes-related autoantibody (GADA, IA-2A or ZnT8A) present at screening, as tested centrally
6. Will be ≥6 weeks from last live immunisation at planned treatment day 1 and be willing to forgo live vaccines during the trial until 6 months post treatment
7. Be willing to comply with intensive diabetes management

E.4

Principal exclusion criteria

Exclusion criteria
1. Type 2 diabetes
2. Evidence of prior or current tuberculosis (TB) infection
3. Clinically significant abnormal full blood count (FBC), renal function or liver function at screening, including:
o Immunodeficient or clinically significant chronic leucopenia, neutropenia, lymphopenia or thrombocytopenia at the screening visit, according to local reference ranges
o Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limit of normal (ULN), at screening
o Evidence of renal dysfunction with creatinine greater than 1.5 times the ULN at screening, adjusted for the age of the patient
o Clinically significant clotting disorder, according to local reference ranges
4. Requiring use of other immunosuppressive or immunomodulation agents, including chronic use of systemic steroids
5. Any active chronic infections at screening, or any active acute or chronic infections at baseline or on treatment day, which would contraindicate any additional immunosuppression
6. Seropositive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection at screening
7. Positive for SARS-CoV-2 based on local testing regimen
8. Unwilling to use appropriate contraception if sexually active during the trial, from date of written informed consent until completion of the 12-month follow up visit
9. Any history of malignancies
10. Current or ongoing use of non-insulin pharmaceuticals that affect glycaemic control
11. Active participation in another T1D treatment interventional trial in the previous 30 days prior to screening (excluding treatment with insulin)
12. Any prior treatment with ATG, Abatacept or anti-CD3
13. Known allergy to ATG or to similar products, or hypersensitivity to rabbit proteins or to any of the excipients
14. Any condition, complicating medical issues, or abnormal clinical laboratory results that the investigator judges may adversely affect trial conduct, cause increased risk to the participant, or compromise the trial results
15. Pregnant and breastfeeding women
16. allergy for rabbit protein

E.5 End points

E.5.1

Primary end point(s)

The area under the stimulated C-peptide response curve over the first 2 hours of a MMTT at 12-months post treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

E.5.2

Secondary end point(s)

• The area under the stimulated C-peptide response curve over the first 2 hours of a MMTT at baseline, 3, 6 and 12 months
• DBS C-peptide measurements at all observation times
• CD4 positive T cells and CD8 positive T cells over 12 months
• HbA1c over 12 months
• Insulin requirements over 12 months
• T1D-associated autoantibodies (GADA, IAA, IA-2A and ZnT8A) over 12 months
• CGM measurements (time in range, time above, time below) over 12 months.
Exploratory outcome measure
• Exploratory study of the effects of treatment on other biomarkers related to immunological changes and β-cell death/ survival in this population

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.1.7.1

Other trial design description

A phase II, multi-centre, randomised, double-blind, placebo-controlled, multi-arm parallel cohort

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

E.8.4

The trial involves multiple sites in the 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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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

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)

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

none

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

2022-01-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-28

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

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