Clinical Study to Test Stem Cells for the Treatment of Long-Term, Non-Healing Venous Leg Ulcers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rheacell GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

16 Jan 2025 → ongoing

Decision date (initial)

2024-12-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512720-11-00

WHO UTN

U1111-1305-5114

ClinicalTrials.gov

NCT06489028

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The aim of this clinical trial is to investigate the efficacy (by monitoring complete wound closure) and safety (by monitoring AEs) of the IP allo-APZ2-CVU, administered topically on target wounds of patients with therapy-resistant non-healing CVU compared to placebo.

Secondary objectives 3

1. The aim is to investigate further efficacy of one dose of 1 x 10⁶ cells/cm² of the IP allo-APZ2-CVU
2. The aim is to investigate the quality of life after one dose of 1 x 10⁶ cells/cm2 of the IP allo-APZ2-CVU
3. The aim is to investigate further safety of one dose of 1 x 10⁶ cells/cm² of the IP allo-APZ2-CVU

Conditions and MedDRA coding

chronic venous ulcers (CVU)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002875-PIP02-24

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients at least 18 years old
2. Chronic venous leg ulcer at lower leg and/or ankle region that has not been present longer than 15 years, diagnosed by Doppler-Duplex sonography, ankle brachial index (ABI, 0.9-1.3; optionally, in case ABI > 1.3 or not measurable: toe brachial index (TBI) ≥0.7)), physical examination and dermatological review
3. Wound size at V1 and V2 between 1 and 25 cm2 as measured by standardized photography
4. If patients have 2 or more ulcers at the same extremity, the target ulcer (defined at V2) has to be separated from the other ulcers with a bridge of epithelialized skin at least 1 cm wide
5. Body mass index between 15 and 50 kg/m²
6. Patients able to understand the nature of the study and able to provide written informed consent prior to any clinical trial procedures
7. Women of childbearing potential must have a negative urine pregnancy test at Visit 1
8. During the course of the clinical trial women of childbearing potential and their male partners must be willing to use highly effective contraceptive methods as defined in the EMA CTCG “Recommendations related to contraception and pregnancy testing in clinical trials", Version 1.2.

Exclusion criteria 16

1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone
2. Uncontrolled Diabetes mellitus i.e. Hemoglobin A1c (HbA1c) >9.0% (75 mmol/mol) (measured by blood test)
3. Peripheral Artery Disease including claudication with need of treatment or intervention
4. Acute deep vein thrombosis diagnosed within 30 days before V1, or untreated deep vein thrombosis
5. Wounds showing size reduction of more than 40% at Visit 2 compared to Visit 1
6. Patients with known hypersensitivity and/or clinical contraindications to the compression systems used in the clinical trial, or inability/unwillingness to tolerate leg ulcer compression systems
7. Acute wound infection of ulcer requiring treatment as judged clinically
8. Current use of medications that are known to influence wound healing i.e. systemic immunosuppressives, cytotoxic medicinal products, systemic steroids (above Cushing-threshold level) at investigator´s discretion
9. Patients who, in the opinion of the investigator, for any reason are unable or unwilling to complete the trial per protocol (e.g. alcohol or substance abuse, not mobile, short life expectancy) or there is an evidence of any other medical condition (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient’s compliance, or place the patient at high risk of complications related to the treatment
10. Any malignancy within the past 5 years, excluding successfully treated carcinoma in situ, basal cell carcinoma or squamous cell carcinoma of the skin without evidence of metastases
11. Pregnant or lactating women
12. Known hypersensitivities to the active substance or to any of the excipients in the IP or the placebo
13. Surgical procedure affecting the CVU, such as bypass or mesh graft performed within two months prior to Visit 1
14. Current or previous (within 30 days of enrollment) treatment with another IP, or participation in another clinical trial, including follow-up phase
15. Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion)
16. Employees of the sponsor, or employees or relatives of the investigator(s)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Efficacy: Complete wound closure at Week 18 already persisting for at least two weeks
2. Safety: Adverse events

Secondary endpoints 10

1. Complete wound closures at each post-baseline follow-up visit
2. Wound size change in percent at each post-baseline follow-up visit
3. Quality of wound healing at each post-baseline follow-up visit
4. Assessment of Quality of Life using the Wound-Quality of Life Questionnaire (W-QoL) as well as the EQ-5D-5L Questionnaire and the SF-36 at V8, V11, V14, V15, V16, V17
5. Pain assessment as per numerical rating scale (NRS) on each post-baseline follow-up visit
6. Duration of wound closure
7. Recurrence of the wound
8. Time to complete wound closure
9. Physical examination and vital signs at V14
10. Assessment of immunogenicity

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rheacell GmbH & Co. KG

Sponsor organisation

Rheacell GmbH & Co. KG

Address

Im Neuenheimer Feld 517, Neuenheim Neuenheim

City

Heidelberg

Postcode

69120

Country

Germany

Scientific contact point

Organisation

Rheacell GmbH & Co. KG

Contact name

office Rheacell (clinical operation department)

Public contact point

Organisation

Rheacell GmbH & Co. KG

Contact name

office Rheacell (clinical operation department)

Third parties 21

Locations

10 EU/EEA countries · 58 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 156 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications