Clinical Trials Register

Summary
EudraCT Number:	2017-002871-24
Sponsor's Protocol Code Number:	AG019-T1D-101
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-05-30
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2017-002871-24

A.3

Full title of the trial

A prospective, multi-center, Phase 1b/2a study to assess the safety and tolerability of different doses of AG019 administered alone or in association with teplizumab in patients with clinical recent-onset Type 1 Diabetes Mellitus (T1D)

A.3.1

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

A.4.1

Sponsor's protocol code number

AG019-T1D-101

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	Intrexon T1D Partners, LLC (IT1D)
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	IT1D
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	Intrexon Actobiotics NV, d/b/a ActoBio Therapeutics
B.5.2	Functional name of contact point	Sven Blomme
B.5.3	Address:
B.5.3.1	Street Address	Industriepark Zwijnaarde 7 C Building D
B.5.3.2	Town/ city	Zwijnaarde
B.5.3.3	Post code	9052
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+32(0)479 93 53 23
B.5.6	E-mail	sblomme@actobio.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	AG019
D.3.4	Pharmaceutical form	Gastro-resistant capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Unknown
D.3.9.1	CAS number	Unknown
D.3.9.2	Current sponsor code	AG019
D.3.9.3	Other descriptive name	AG019
D.3.9.4	EV Substance Code	SUB192089
D.3.10	Strength
D.3.10.1	Concentration unit	million CFU million colony forming units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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.IMP: 2
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Teplizumab
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	Teplizumab
D.3.9.1	CAS number	876387-05-2
D.3.9.2	Current sponsor code	MGA031
D.3.9.3	Other descriptive name	TEPLIZUMAB
D.3.9.4	EV Substance Code	SUB35383
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	1
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)	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	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	Gastro-resistant capsule, hard
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for 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

Recent-onset Type 1 Diabetes mellitus (T1D)

E.1.1.1

Medical condition in easily understood language

Recent-onset Type 1 Diabetes mellitus (T1D)

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10067584
E.1.2	Term	Type 1 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the safety and tolerability of different doses of AG019 alone as well as in association with teplizumab.

E.2.2

Secondary objectives of the trial

To obtain pharmacodynamics (PD) data of AG019 alone as well as AG019 in association with teplizumab

To determine the potential presence of sAGX0407 or its secreted proteins in systemic circulation (safety – systemic exposure) and the presence of L. lactis bacteria in fecal excretion (local exposure): pharmacokinetic (PK) profile

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or non-pregnant, non-lactating females, 18-40 years of age (both inclusive) or 12-17 years of age (both inclusive)
- Diagnosis of diabetes according to the ADA recommended criteria
- Evidence of auto-antibodies to at least 1 of the following β-cell autoantigens: insulin, IA-2, GAD65, ZnT8
- Stimulated C-peptide measured during 4h Mixed Meal tolerance Test (MMTT) > 0.2 nmol/L
- The first administration of AG019 should occur no later than 150 days post diagnosis
- Body weight ≥ 33kg
- Willing and medically able to postpone live vaccine immunizations for at least 8 weeks after randomization
- Ability and willingness of patients to participate fully in all aspects of this clinical study
- Written informed consent obtained and documented
- Willingness to use a continuous glucose monitoring device and willingness to comply with the protocol defined glucose monitoring
- Total bilirubin ≤1.0 x upper limit of normal (ULN), Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤1.5 x ULN, ≥1,000 lymphocytes/µL, ≥1,000 polymorphonuclear neutrophils (PMN)/µL, ≥100,000 platelets/µL, Hgb ≥10 g/dL, Serum Creatinin ≤1.5 x ULN, eGFR ≥60 mL/min/1.73m², INR ≤0.1 above upper limit of normal, Absence of clinically significant age appropriate abnormalities on all other lab values, except for abnormalities directly attributable to T1D

E.4

Principal exclusion criteria

- Previous history of serious cytokine release syndrome to teplizumab or other humanized anti-CD3 monoclonal antibodies with no or minimal capacity to bind Fc receptors
- Current use of any systemic antibiotics, except for the following: metronidazole (metronidazole), nalidixic acid (first generation quinolone), trimethoprim, sulfamethoxazole (sulfonamide) and/or a combination of both in a ratio 1/19 (sulfonamides)
- Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to randomization
- Participation in another investigational drug trial within 12 weeks prior to the first study drug intake and during participation in this study
- History of recurrent infections, other autoimmune diseases, cardiac disease, malignancy, or any other (chronic) medical condition which, in the investigator’s opinion, could compromise participant safety
- Documented history of human immunodeficiency virus (HIV), Hepatitis Virus Type C (HCV), Hepatitis Virus Type B (HBV) infection
- Evidence of active infection with Epstein-Barr Virus (EBV) or cytomegalovirus (CMV)
- Untreated hypothyroidism or active Graves’ disease
- Evidence of any active infection with the exception of superficial skin infections
- Vaccination with live virus or organism within 8 weeks prior to randomization
- Evidence of active or latent tuberculosis (TB)
- Administration of anti-CD3 antibody in past year
- Current therapy with any other anti-diabetic agents other than insulin (MDI, CSII or analogue). Current or planned therapy with experimental (i.e., unapproved) insulin
- Use of medications known to influence glucose tolerance
- Daily use of non-steroidal anti-inflammatory agents
- Compromised GI mucosal integrity or motility, not attributable to T1D (i.e., recent diarrhea, gluten sensitive enteropathy, inflammatory bowel disease, irritable bowel syndrome), or current use of medications known to influence GI motility
- Inability to swallow size 1 capsules
- Alcohol or illicit drug consumption, which in the opinion of the investigator, may interfere with the patient’s ability to comply with the study procedures
- Active psychiatric problems, which in the opinion of the investigator, may interfere with the patient’s ability to comply with study procedures

E.5 End points

E.5.1

Primary end point(s)

Analysis of the incidence of treatment-emergent adverse events (TEAEs) collected up to the 6-month follow-up visit.

E.5.1.1

Timepoint(s) of evaluation of this end point

Cohorts 1-4 (AG019 only): Study day 1, 4, 7, 12, 28, 56, 90, 180
Cohorts 5-6 (AG019 + teplizumab): Study day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 28, 56, 90, 180

E.5.2

Secondary end point(s)

The PD activity of the study drug(s) will be assessed by measurement of biomarkers in blood and serum samples. Relevant parameters will be assessed, including immune markers for effect, relevant T1D parameters and relevant cytokines.

Following parameters will be assessed for analysis of systemic and local exposure to L. lactis (PK profile):
• Presence of live L. lactis clinical strain bacteria in whole blood
• Measurable serum levels of hIL-10 and hPINS
• Presence of L. lactis clinical strain bacteria in fecal excretion

Safety information collected at all other time points will be assessed as secondary end points.

E.5.2.1

Timepoint(s) of evaluation of this end point

PD: Study day1, 12, 56, 180, 270 and 360
PK: Study day 12, 56 and 90

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

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)

Yes

E.7.1.1

First administration to humans

Yes

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

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

Yes

E.8.1.7.1

Other trial design description

Phase 1b:Not controlled, open; Phase 2a: controlled, double blind, parallel group, placebo

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

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

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

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)

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

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)

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

2018-10-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-06-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-10-13

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