| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic venous ulcers (CVU) |
|
| E.1.1.1 | Medical condition in easily understood language |
| The root of venous ulcers is increased pressure of blood in the vessels (veins) of the lower leg causing swelling and damage to the skin leading eventually to a painful non healing wound called ulcer. |
|
| 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 | 10066677 |
| E.1.2 | Term | Chronic leg ulcer |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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. |
|
| E.4 | Principal exclusion criteria |
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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary efficacy endpoint:
1. Complete wound closure at Week 18 already persisting for at least two weeks.
Primary safety endpoint:
2. Adverse events (AEs). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary efficacy endpoint:
1. Week 18.
Primary safety endpoint:
2. A priori specification not possible; between Screening and Month 10. |
|
| E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints:
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.
Secondary safety endpoints:
9. Physical examination and vital signs at V14. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy endpoints:
1. Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10.
2. Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10.
3. Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10.
4. Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10.
5. Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10.
6. Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10.
7. Week 6, 12, 18.
8. Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10.
Secondary safety endpoints:
9. Week 18. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| 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 | 36 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
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