Study to investigate the efficacy and safety of allo-APZ2-CVU on wound healing of therapy-resistant chronic venous ulcer (CVU)

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

18 Aug 2021 → 25 Nov 2025

Decision date (initial)

2024-03-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

RHEACELL GmbH & Co. KG

External identifiers

EU CT number

2023-510162-27-00

EudraCT number

2020-004960-24

WHO UTN

U1111-1301-6596

ClinicalTrials.gov

NCT04971161

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Efficacy

The aim of this clinical trial is to investigate the efficacy (by monitoring the wound closure of CVUs) and safety (by monitoring adverse events [AEs]) of three doses of the investigational medicinal product (IMP) allo-APZ2-CVU, topically administered on target wounds of patients with CVU compared to placebo.

Conditions and MedDRA coding

Chronic venous ulcers (CVU)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

IPD plan description

To be decided

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male or female patients at least 18 years old;
2. Chronic venous leg ulcer (as defined by the current AWMF guidelines: therapy-resistant ulcer that shows no tendency to heal within 3 months despite of optimal phlebological therapies or has not fully healed within 12 months) at lower leg and/or ankle region and has not been present longer than 15 years, diagnosed by doppler or duplex sonography, ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review;
3. Wound size of target ulcer between 1 and 50 cm2 measured by a standardized photography at the screening visit;
4. If patients have 2 or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of epithelialized skin from other ulcers (the largest ulcer should be the target ulcer, if not decided otherwise at discretion of the investigator; the target ulcer is defined at Visit 1);
5. Body mass index between 15 and 50 kg/m²
6. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
7. Women of childbearing potential must have a negative blood pregnancy test at Visit 1;
8. Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial.

Exclusion criteria 18

1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
2. Diabetes mellitus that has to be confirmed by blood test (Hemoglobin A1c >7.5%);
3. Peripheral Artery Disease including claudication with need of treatment;
4. Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
5. Unable to tolerate leg ulcer compression bandage;
6. Infection of the target ulcer requiring treatment as judged clinically;
7. All diagnosed disorders, unrelated to CVU, that are influencing wound healing of the target wound at investigator’s discretion;
8. Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);
9. Patient 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 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. Any known allergies to components of the IMP;
13. Prior surgical procedures such as bypass or mesh-graft treatment at target leg within 2 months prior to Visit 1 at target leg;
14. Patients with significant ulcer healing or wound size enlargement of more than 25% at Visit 2 compared to Visit 1;
15. Treatment of target ulcer with active wound care agents (e.g. Iruxol®N), which have not been paused 14 days before IMP application;
16. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
17. Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion);
18. Employees of the sponsor, or employees or relatives of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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

Secondary endpoints 9

1. Wound size change in percent at each post-baseline follow-up visit;
2. Time to complete wound closure;
3. Complete wound closures at each post-baseline follow-up visit;
4. Duration of wound closure;
5. Recurrence of the wound;
6. Quality of wound healing at each post-baseline follow-up visit;
7. Assessment of Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14;
8. Pain assessment as per numerical rating scale on each post-baseline efficacy follow-up visit;
9. Physical examination and vital signs at V14.

Investigational products

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

Test 3

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 8

Locations

1 EU/EEA country · 36 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 25 files

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

Application history

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