E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic venous ulcers (CVU) |
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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. |
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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 | 100000004858 |
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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 size reduction of CVUs) and safety (by monitoring adverse events [AEs]) of two doses of allo-APZ2-CVU topically administered on wounds of patients with CVU. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients aged 35 to 85 years; 2. Chronic venous leg ulcer (as defined by the current AWMF guidelines: therapy resistant ulcer that shows no improvement within 3 months despite of optimal phlebological therapies or is not healed within 12 months) diagnosed by doppler ultrasonography (DUS), ankle brachial index (ABI, 0.9–1.3), physical examination and dermatological review; 3. Wound size of target ulcer between 1.5 and 100 cm2 measured by a standardized photography at the screening visits (Visit 1 and Visit 2); 4. Wound location below knee; 5. If patients are suffering from 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); 6. Body mass index (BMI) between 20 and 45 kg/m²; 7. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure; 8. Women of childbearing potential must have a negative blood pregnancy test at Visit 1 9. Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial. |
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E.4 | Principal exclusion criteria |
1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone; 2. Current use of systemic steroid medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent); 3. Diabetes mellitus that has to be evaluated by blood test (Haemoglobin A1c [HbA1c] >7.5%); 4. Peripheral Artery Disease (PAD) including claudication with need of treatment; 5. Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis; 6. Unable to tolerate leg ulcer compression bandage; 7. Infection of the target ulcer requiring treatment as judged clinically; 8. Any chronic dermatological disorders diagnosed at the investigator’s discretion; 9. Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound; 10. Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level); 11. Known abuse of alcohol, drugs, or medicinal products; 12. Cancerous or pre-cancerous lesions adjacent to the target wound; 13. Patients anticipated to be unwilling or unable to comply with the requirements of the protocol; 14. Pregnant or lactating women; 15. Systemic infectious disease diagnosed by serology testing for human immunodeficiency virus (HIVĖ1, HIV-2); 16. Any known allergies to components of the IMP; 17. Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to Visit 1; 18. Patients with significant ulcer healing or wound size enlargement of more than 25% at Visit 2 compared to Visit 1; 19. Treatment of target ulcer with active wound care agents (e.g. iruxol, local antibiotics or silver dressings), which have not been paused 14 days before IMP application; 20. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial; 21. Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion); 22. Evidence of any other medical conditions (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; 23. Employees of the sponsor, or employees or relatives of the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Primary efficacy endpoint: • Percentage of wound size reduction at Week 12, or last available post-baseline measurement of Weeks 6, 8 or 10 if the Week 12 measurement is missing (last observation carried forward [LOCF]). 2. Primary safety endpoint: Adverse events.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Week 12, or last available post-baseline measurement of Weeks 6, 8 or 10 if the Week 12 measurement is missing. 2. During all patient visits except screening. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: 1. Percentage of wound size reduction ; 2. Absolute wound size reduction; 3. Proportion of patients achieving complete wound closure; 4. Time to first complete wound closure; 5. Proportion of patients achieving 30% wound closure; 6. Time to first 30% wound closure; 7. Epithelialization; 8. Assessment of further wound healing parameters: formation of granulation tissue and wound exudation; 9. Pain assessment as per numerical rating scale (NRS); 10. Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire; 11. Assessment of dermatology-specific quality of life based on the Dermatology Life Quality Index (DLQI) questionnaire;
Secondary safety endpoint: 12. Physical examination and vital signs at Week 6.1 and 12; |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 (without LOCF); 2. Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12; 3. Weeks 2, 3, 4, 6, 8, 10, 12, and at any time point; 4. A priori specification not possible; between baseline and week 12 post baseline; 5. Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, 12, and at any time point; 6. A priori specification not possible; between baseline and week 12 post baseline; 7. Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12; 8. Day 0 before IMP application, Days 1 and 8, Weeks 2, 3, 4, 6, 6.2, 8, 10, and 12; 9. Days 0, 1 and 8, Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12; 10. Day 0 and Weeks 4, 8 and 12; 11. Day 0 and Weeks 4, 8 and 12; 12. Week 6.1 and 12; |
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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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Safety and efficacy in patients |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 9 |
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 | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |