Clinical Trials Register

Summary
EudraCT Number:	2022-000492-39
Sponsor's Protocol Code Number:	XIN-XSTEM-201
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-04-08
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

Sweden - MPA

A.2

EudraCT number

2022-000492-39

A.3

Full title of the trial

A multi-centre, randomised, single-blind Phase I/IIa study to evaluate the safety, tolerability and efficacy of a single topical dose of allogeneic integrin α10β1-selected mesenchymal stem cells (XSTEM-VLU) in patients with difficult-to-heal venous leg ulcers

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

XIN-XSTEM-201

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	Xintela AB
B.1.3.4	Country	Sweden
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	Xintela AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CTC Clinical Trial Consultants AB
B.5.2	Functional name of contact point	Clinical Research Manager
B.5.3	Address:
B.5.3.1	Street Address	Dag Hammarskjölds väg 10B
B.5.3.2	Town/ city	Uppsala
B.5.3.3	Post code	SE-75237
B.5.3.4	Country	Sweden
B.5.4	Telephone number	0046705290262
B.5.6	E-mail	frida.kaver@ctc-ab.se

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	XSTEM-VLU
D.3.4	Pharmaceutical form	Cutaneous suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Allogeneic integrin a10β1-selected and expanded mesenchymal stem cells from human adipose tissue (XSTEM)
D.3.9.3	Other descriptive name	XSTEM
D.3.9.4	EV Substance Code	SUB266742
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000000
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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Cutaneous solution
D.8.4	Route of administration of the placebo	Topical

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Difficult-to-heal venous leg ulcers

E.1.1.1

Medical condition in easily understood language

Difficult-to-heal venous leg ulcers

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10047260
E.1.2	Term	Venous ulceration
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue 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 characterise the safety and tolerability of a single dose of XSTEM-VLU and vehicle as add on to standard wound care in patients with difficult-to-heal venous leg ulcers.

E.2.2

Secondary objectives of the trial

To assess preliminary efficacy of a single dose of XSTEM-VLU and vehicle as add on to standard wound care in patients with difficult-to-heal venous leg ulcers.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For inclusion in the study, patients must fulfil the following criteria:
1. Willing and able to give written informed consent for participation in the study.
2. Male or female patient aged ≥18 years at the time of the screening visit (Visit 1).
3. BMI ≥18.5 and ≤40.0 kg/m2.
4. Wound located on the lower part of the lower limb, with a predominant venous component.
5. Target wound has failed to heal despite standard wound care including compression therapy for a minimum of 6 weeks prior to the screening visit (Visit 1), as judged by the Investigator.
6. Patient who has been compliant to their prescribed compression therapy over the (at least) 6 weeks prior to the screening visit (Visit 1), as judged by the Investigator.
7. A surface area of the target wound of ≥2.00 and ≤40.00 cm2 measured using the SeeWound (or other wound planimetry measure) after standard wound care attention at the screening visit (Visit 1).
8. WOCBP must practice abstinence (only allowed when this is the preferred and usual lifestyle of the patient) or agree to use a highly effective method of contraception with a failure rate of <1 % to prevent pregnancy (combined [oestrogen 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 [IUD] or intrauterine hormone-releasing system [IUS]) from at least 4 weeks prior to ATIMP administration to 3 months after ATIMP administration. Female patients must refrain from donating eggs from the date of ATIMP administration until 3 months after ATIMP administration. Any male partner of a female study patient must agree to use a condom during the same period.
Women of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or post-menopausal defined as 12 months of amenorrhea.
Male patients must be willing to use condoms, be vasectomised or practice abstinence (only allowed when this is the preferred and usual lifestyle of the patient) to prevent pregnancy and drug exposure of a partner, as well as refrain from donating sperm from the date of ATIMP administration until 3 months after ATIMP administration. Any female partner of a male study patient must agree to use a contraceptive method with a failure rate of < 1 %, as described above, to prevent pregnancy.

E.4

Principal exclusion criteria

Patients must not enter the study if any of the following exclusion criteria are fulfilled:
1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient’s ability to participate in the study.
2. Any planned major surgery during the study.
3. Signs or symptoms of clinically significant ongoing infection (in the target wound) requiring anti-microbial treatment (including antibiotics) during the screening period (from Visit 1) until randomisation (Visit 5), as judged by the Investigator. Topical anti-microbial therapy being part of a patient’s standard wound care is allowed prior to Visit 5.
4. History of any autoimmune disease, such as but not limited to systemic lupus erythematosus, Addison’s disease, Crohn’s disease and type I diabetes mellitus.
5. B-HbA1C value ≥52 mmol/mol at the time of the screening visit (Visit 1).
6. Plaque psoriasis or any other skin disease that could interfere with the outcome of the study, as judged by the Investigator.
7. Ankle-brachial index <0.7 at the screening visit (Visit 1).
8. History of any malignancy within the past 5 years.
9. Target wound diagnosed as a malignant wound, neuropathic wound, pressure wound or osteomyelitis.
10. Non-target wound within 2 cm of the target wound.
11. Current use of systemic corticosteroids which in the opinion of the Investigator could interfere with the quality of, or the healing properties of the skin.
12. Patients who are immunocompromised due to disease (e.g., HIV) or for other reasons such as the use of systemic immunosuppressants.
13. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibodies and/or HIV.
14. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to XSTEM-VLU, DMSO, dextran or any other components of the therapy media.
15. Patients who are pregnant, currently breastfeeding, or intend to become pregnant during the first 3 month after ATIMP administration.
16. Planned treatment or treatment with another investigational drug from signing of the informed consent until Visit 16.
17. Medical, psychiatric, cognitive, or other conditions that may compromise the patient’s ability to understand the patient information, give informed consent, comply with the study protocol or complete the study, as judged by the Investigator.

Additional exclusion criterion evaluated at Visit 5 (pre-dose):
18. A surface area of the target wound of <1.50 or >50.00 cm2 measured using SeeWound (or other planimetry measure).

E.5 End points

E.5.1

Primary end point(s)

-Frequency, seriousness and intensity of adverse events (AEs)
-Local tolerability, including need for debridement and clinical signs of wound infection
-Clinically significant changes in vital signs, electrocardiogram (ECG), safety laboratory measurements (haematology, clinical chemistry, coagulation) and physical examination findings

E.5.1.1

Timepoint(s) of evaluation of this end point

Regularly throughout the study, from dose until end of study visit.

E.5.2

Secondary end point(s)

-Wound area, measured weekly during 10 weeks post-administration and at 4 months, including (but not limited to):
- Wound area reduction from baseline (absolute and percentage)
- Proportion of patients with re-epithelialization of ≥95% and ≥50% of the wound area measured
at baseline
- Time to re-epithelialization of ≥95% and ≥50% of the wound area measured at baseline
(The analysis of wound area may be further specified in the statistical analysis plan [SAP])

-Pain for the target wound and the affected leg, separately, assessed weekly during 10 weeks post-administration and at 4 months, using a Visual Analogue Scale (VAS)

- Scar formation (Patient and Observer Scar Assessment Scale [POSAS] score) at week 10 and at 4 months

E.5.2.1

Timepoint(s) of evaluation of this end point

- Wound area, measured weekly during 10 weeks post-administration and at 4 months.
- Pain for the target wound and the affected leg, separately, assessed weekly during 10 weeks post-administration, and at 4 months.
- Scar formation at week 10 and at 4 months

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

Phase I/IIa

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

Yes

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

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

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

LSLV

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)

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

2022-07-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-18

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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