Clinical Trials Register

Summary
EudraCT Number:	2021-004588-29
Sponsor's Protocol Code Number:	TA799-101
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-10-04
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 - BfArM

A.2

EudraCT number

2021-004588-29

A.3

Full title of the trial

A randomized, double-blind trial to evaluate the safety and efficacy of apraglutide in subjects with Grade II to IV (MAGIC) steroid refractory gastrointestinal (GI) acute graft versus host disease on best available therapy

A.3.1

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

Efficacy and Safety of apraglutide in steroid refractory gastrointestinal acute graft versus host disease

A.3.2

Name or abbreviated title of the trial where available

Proof-of-concept trial of apraglutide in GVHD

A.4.1

Sponsor's protocol code number

TA799-101

A.5.4

Other Identifiers

Name:

IND

Number:

156438

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	VectivBio AG
B.1.3.4	Country	Switzerland
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	VectivBio AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	VectivBio AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Aeschenvorstadt 36
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4051
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41615513030
B.5.6	E-mail	clinicaltrial.enquiries@vectivbio.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	Apraglutide
D.3.2	Product code	TA799
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Apraglutide
D.3.9.1	CAS number	1295353-98-8
D.3.9.2	Current sponsor code	TA799; FE 203799
D.3.9.3	Other descriptive name	apraglutide
D.3.9.4	EV Substance Code	SUB193006
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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)	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

Acute graft versus host disease (GVHD)

E.1.1.1

Medical condition in easily understood language

inflammatory disorder

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10075160
E.1.2	Term	Graft versus host disease in gastrointestinal tract
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10075161
E.1.2	Term	Graft versus host disease in GI tract
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10066264
E.1.2	Term	Acute graft versus host disease in intestine
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10066260
E.1.2	Term	Acute graft versus host disease
E.1.2	System Organ Class	10021428 - Immune system disorders

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

Primary Objective:
To assess safety and tolerability of apraglutide in subjects with SR GI-aGVHD of the mid-lower GI tract who are treated with SS and with RUX for 0–3 days
Key Efficacy Objective:
To evaluate the SR GI-aGVHD response rate at Day 56 in subjects with SR GI-aGVHD Grade II to IV (Mount Sinai aGVHD International Consortium [MAGIC]; Harris 2016) treated with apraglutide, SS, and RUX compared with SS and RUX alone (BAT)

E.2.2

Secondary objectives of the trial

Key Secondary Objectives:
•Evaluate the SR GI-aGVHD response rate at Days 14,28,90,120,150, & 180 in subjects with GI-aGVHD treated with apraglutide and BAT compared with BAT
•Estimate overall GVHD response rate at Days 14,28,56,90,120,150, & 180
•Estimate duration of response from Day 56
Secondary Efficacy Objectives:
•Assess durability of GI response:
-Assess time to complete GI-GVHD response and FFS
-Assess individual course of GI-GVHD response and overall GVHD response at Days 14, 28, 56, 90, 120, 150, and 180
-GI-GVHD response in subjects retreated due to GI-GVHD flare up to Day 180 post initial apraglutide dose
•Incidence of GI-GVHD flare up to Day 180 following earlier cessation due to complete response
•Assess duration of response from Day 29, non relapse mortality, overall survival, individual time courses, doses of BAT up to Day 90 post-initial apraglutide dose and nutrition status
•Measure incidence of infections,sepsis,malignancy relapse, secondary malignancies

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent for this trial prior to any trial specific assessment. A signed assent form will also be required for any subjects under the age of 18 years
2. Male or female subjects aged 12 years or above at the time of consent and who weigh a minimum of 40 kg. Only subjects of 18 years and above will be included in Germany.
3. Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible
4. Evident myeloid and platelet engraftment (confirmed prior to trial medication start):
a) Absolute neutrophil count >1000/mm3
AND
b) Platelets ≥20,000/mm3
Use of growth factor supplementation (granulocyte-colony stimulating factor and granulocyte-macrophage-colony stimulating factor) and transfusion support is allowed
5. Histologically diagnosed GI-aGVHD at screening (with clinically confirmed SR GI-aGVHD at RUX start and prior to apraglutide start) defined as subjects administered SS, given alone or combined with calcineurin inhibitors (CNI) and either:
a) Disease progression based on organ assessment after 3 days
OR
b) Did not improve after 7 days of treatment with MP 2mg/kg/day equivalent,
OR
c) Progressed to a new organ after treatment with MP 2 mg/kg/day equivalent for skin and upper GI-aGVHD,
OR
d) Recurred during or after a steroid taper
All subjects must have Stage 1–4 lower GI-aGVHD at enrollment
6. Treated with SS plus RUX (RUX at the recommended dose twice daily for 0–3 days). CNI are allowed as co-medication, if needed
7. Women of childbearing potential must agree to use a highly effective method of contraception during the trial and for 4 weeks after the EOT visit. Such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation injectable, implantable); intrauterine device; intrauterine hormone-releasing
system; bilateral tubal occlusion; vasectomized partner. Oral methods of hormonal contraception are to be combined with another accepted method for contraception. To be considered sterilized or infertile, females must have undergone surgical sterilization (bilateral tubectomy, hysterectomy, or bilateral ovariectomy) or be post-menopausal (defined as at least 12 months amenorrhea
without an alternative medical cause, may be confirmed with follicle-stimulating hormone test in case of doubt). Women who do not engage in heterosexual intercourse will be allowed to join the trial without contraception following a thorough discussion with the Investigator to determine if this is feasible for the subject. The following methods are not considered acceptable methods of contraception: calendar, ovulation, symptothermal, post-ovulation methods, withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method
8. Male subjects with a female partner of childbearing potential must commit to practice methods of contraception and abstain from sperm donation during the trial and for 2 weeks after the EOT visit.
Nevertheless, if their partners are women of childbearing potential, they must agree to practice contraception and use a highly effective method of contraception during the trial and for 4 weeks after the EOT visit.
Such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal
contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion

E.4

Principal exclusion criteria

1. Treatment with any systemic GVHD therapy other than SS and RUX including methotrexate and mycophenolate mofetil. For subjects on GVHD prophylaxis (ciclosporin A, tacrolimus, sirolimus, everolimus, or anti-thymocyte globulin) this medication can be continued
2. Concomitant treatment with Janus kinase inhibitor therapy for any other indication after initiation of current alloSCT conditioning
3. Presence of any systemic corticosteroid therapy for indications other than aGVHD within 7 days prior to screening. Low doses of prednisolone/hydrocortisone for adrenal suppression are allowed
4. Failed alloSCT within the past 6 months before randomization
5. Presence of SR GI-aGVHD occurring after non-scheduled donor lymphocyte infusion administered for pre-emptive treatment of malignancy recurrence
6. Previous administration of any investigational treatment agent within 30 days prior to screening or within five half-lives of the trial medication, whichever is greater. Subjects who have received placebo in a previous study during this period may be included.
7. Known or suspected hypersensitivity to GLP-1 or GLP-2 analogs or apraglutide excipients
8.Any use of enteral glutamine or growth factors such as native GLP-2, GLP-1 or GLP-2 and GLP-1 analogs within 6 months prior to randomization
9.Inability to understand or adhere to the trial visit schedules and other protocol requirements, including subjects not willing to comply due to drug/alcohol abuse or any condition that would interfere with full participation in the trial, including administration of trial medication and attending required trial visits; pose a significant risk to the subject; or interfere with interpretation of trial data
10. Less than 2 weeks anticipated survival at screening
11.Known significant respiratory disease including subjects who are on mechanical ventilation or who have known resting O2 saturation <90% by pulse-oximetry on room air
12.Presence of severely impaired renal function requiring dialysis, or has an estimated creatinine clearance <29 mL/min/1.73m2 measured or calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI; confirmed within 48 hours prior to randomization)
13.Presence of decompensated liver cirrhosis Child-Pugh Class B and C
14.Clinically significant or uncontrolled cardiac disease including acute myocardial infarction within 6 months prior to randomization, uncontrolled hypertension, New York Heart Association Class III or IV congestive heart failure, unstable angina within last 6 months prior to screening, or presence of severe arrhythmia
15.Requirement for vasopressor or inotropic support (within 30 days to randomization)
16.Presence of uncontrolled cholestatic disorders or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver
17.Presence of relapsed primary malignancy, or treatment for relapse after the alloSCT, or requirement for rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse
18.Presence of newly diagnosed malignancies (intestinal- or liver malignancies) or history of chronic gall bladder or bile duct inflammation or biliary obstruction unless cholecystectomy was performed prior to screening
19.Presence of GI tumors or colonic polyps that are not removed
20.Presence of an active uncontrolled infection such as active viral infection (confirmed by peripheral blood viral load) including Epstein Barr virus, SARS-COV-2 virus, human immunodeficiency virus, hepatitis B virus, or hepatitis C virus. Cytomegalovirus reactivation is permitted as long as no evidence of pulmonary disease is present. Please refer to protocol.
21.Known chronic GVHD
22.Known active gut inflammation not related to GI-aGVHD
23.History of progressive multifocal leuko-encephalopathy
24.Known pregnant or nursing (lactating) women
25.Known major abdominal surgery in the last 6 months prior to screening (surgical feeding tube placement or other minimally invasive surgery allowed)
26.History of clinically significant intestinal adhesions increasing the risk of GI obstruction and/or GI contrast trial(s) suggesting subacute intestinal obstruction or stricture within 6 months prior to screening
27.Presence of severe constipation (no stool in the past 48 hours prior to randomization) which is not managed by dietary recommendations, laxatives or cathartic medications
28.History of intestinal pseudo-obstruction and refractory coeliac disease (within 6 months prior to screening)
29.Any previous use of GLP-2 analogues or known ADA
30.Liver enzyme deviation as described in the exclusion criterion #29 in the protocol

E.5 End points

E.5.1

Primary end point(s)

• Gastrointestinal-aGVHD response at Day 56 in subjects with GI-aGVHD treated with apraglutide, SS, and RUX compared with SS and RUX alone (BAT)

E.5.1.1

Timepoint(s) of evaluation of this end point

After day 56 is completed for all subjects

E.5.2

Secondary end point(s)

• Gastrointestinal-aGVHD response at Days 14, 28, 90, 120, 150, and 180 in subjects with GI-aGVHD treated with apraglutide, SS, and RUX compared
with SS and RUX alone (BAT).
• Overall response at Days 14, 28, 56, 90, 120, 150, and 180
• Duration of response from Day 56

E.5.2.1

Timepoint(s) of evaluation of this end point

When Days 14, 28, 56, 90, 120, 150, and 180 are completed by all subjects

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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

Belgium

Germany

Portugal

Spain

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

The end of the trial is defined as the last subject’s last visit.

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

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)

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Elderly

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)

All subjects are expected to return to standard of care

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

2021-12-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-01

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

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