Clinical Trials Register

Summary
EudraCT Number:	2016-003947-12
Sponsor's Protocol Code Number:	Treg003
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-02-02
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

Germany - PEI

A.2

EudraCT number

2016-003947-12

A.3

Full title of the trial

Treatment of steroid-resistant chronic graft-versus-host-disease with donor-derived regulatory T cells

Therapie der Steroid-refraktären chronischen Graft-versus-Host-Erkrankung mit regulatorischen Spender-T-Zellen

A.3.1

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

Treatment of steroid-resistant chronic graft-versus-host-disease with regulatory T cells

A.3.2

Name or abbreviated title of the trial where available

Treg Therapy

Treg Therapie

A.4.1

Sponsor's protocol code number

Treg003

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	Freistaat Bayern represented by University of Regensburg represented by Kaufmännischer Direktor
B.1.3.4	Country	Germany
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	EC, Horizon 2020, TREGeneration
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Hospital Regensburg
B.5.2	Functional name of contact point	Clinical Trial Coordination
B.5.3	Address:
B.5.3.1	Street Address	Franz-Josef-Strauss-Allee 11
B.5.3.2	Town/ city	Regensburg
B.5.3.3	Post code	93053
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049 9419445580
B.5.5	Fax number	00499419445148
B.5.6	E-mail	matthias.edinger@ukr.de

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	Expanded Tregs
D.3.2	Product code	RegTivex
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	none
D.3.9.2	Current sponsor code	RegTivex
D.3.9.3	Other descriptive name	expanded regulatory T cells
D.3.10	Strength
D.3.10.1	Concentration unit	million organisms/g million organisms/gram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	3 to 10
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	Yes
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Treatment of steroid-resistant chronic graft-versus-host disease with donor-derived regulatory T cells

Therapie der Steroid-refraktären chronischen Graft-versus-Host-Erkrankung mit regulatorischen Spender-T-Zellen

E.1.1.1

Medical condition in easily understood language

graft-versus-host disease

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10021428
E.1.2	Term	Immune system disorders
E.1.2	System Organ Class	10021428 - Immune system 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 examine the safety and MTD Level of in vitro expanded donor regulatory T cells for the Treatment of patients with chronic GVHD

E.2.2

Secondary objectives of the trial

To assess the clinical response to Treg treatment
To assess immunologic effects of Treg treatment
To determine predictors of clinical Response

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The following criteria on screening examination have to be fulfilled:
• Steroid-refractory moderate to severe cGVHD despite use of two or more agents (failure of 2nd line treatment). Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D) despite the use of prednisone at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of other glucocorticoids) without complete resolution of signs and symptoms and continuing moderate to severe cGVHD.
• Steroid-dependent cGVHD as indicated if >0.25 mg/kg/d prednisone are needed to prevent cGVHD recurrence or progression on 2nd line treatment or subsequent treatment lines as illustrated by two failed attempts to taper with a more than 8 wks interval
• No dose-escalation of glucocorticoids beyond the maximum dose of the prior cGVHD treatment line within 4 wks of enrolment
• No addition of other immunosuppressive medications (e.g., calci-neurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrolment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of the drug
• ECOG performance status 0-2 (Appendix X, section X)
• Participants must have adequate organ function as defined below:
Hepatic: Adequate hepatic function (total bilirubin <2.0 mg/dl-exception permitted in participants with Gilbert’s Syndrome; AST (SGOT)/ALT (SGPT) ≤2x ULN), unless hepatic dysfunction is a manifestation of proven or presumed cGVHD. Abnormal LFTs in the context of active cGVHD involving other organ systems is permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD.
Pulmonary: FEV1 ≥ 50% of predicted, unless pulmonary dysfunction is deemed to be due to chronic GVHD.
• Age 18 -75 y
• Written informed consent of patient

E.4

Principal exclusion criteria

• Age <18 y and >75 y
• No previous steroid therapy
• Severe psychiatric disorders
• Presumed life expectancy < 4 wks
• Lack of informed consent from patient
• Donors from outside EU (NMDP, Canadian donor registrar)
• Participation in another interventional clinical trial according to the AMG (Arzneimittel¬gesetz) within 30 days prior to inclusion
• T cell-depleting antibody therapy within the last 30d before enrolment
• Pregnant or nursing woman. Sexually active women with childbearing potential or sexually active male patients unwilling to use an effective form of contraception during participation in the study from time of inclusion until 2 months after Treg therapy

E.5 End points

E.5.1

Primary end point(s)

Toxicity and MTD of Treg-infusion at 4 weeks

E.5.1.1

Timepoint(s) of evaluation of this end point

1month after therapy

E.5.2

Secondary end point(s)

Feasibility of donor Treg infusion
Clinical response of Treg-treated patients at 12 & 24wks after Treg infusion
Immunologic effects of Treg treatment within 12 weeks

E.5.2.1

Timepoint(s) of evaluation of this end point

wk 1, 4, 8, 12, 24

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

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

IMP used in clinical trial EudraCT number 2012-002685-12

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

Yes

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

Trial is terminated after the last study 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

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)

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)

Yes

F.1.3.1

Number of subjects for this age range:

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.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)

Standard of care treatement

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

2017-06-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-03-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-03-28

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