E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The autologous cultured skin substitute (Tiscover) or acellular donor dermis (AS210) is applied to patients with chronic (arterio-) venous leg wounds. |
chronic (arterio-) venous leg wounds. |
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E.1.1.1 | Medical condition in easily understood language |
Chronic, hard to heal lower leg wounds due to insufficient blood/artery |
Langdurig open been wonden veroorzaakt door vaatlijden welke geen genezingstendens hebben. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
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 |
Determine the safety and relative efficacy of Tiscover® or AS210
- Safety is assessed by describing the number and type of adverse events;
- Efficacy is assessed by determining:
- Time to heal
- Wound size reduction
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E.2.2 | Secondary objectives of the trial |
- Recurrence:
Number and percentage of recurrence of ulceration at 3 and 6 months after wound closure.
- Quality of the healed skin:
Closed wounds will be visually assessed regarding to scarring.
- Quality of life
Quality of life measured at baseline, when closed, and at 3 and 6 months follow up. Quality of life will be assessed using
o SF36; Quality of life score
o VAS (visual analogue scale) for experienced pain.
- Take rate of individual Tiscover and AS210 patches.
o Number and percentage of Tiscover or AS210 patches present on the wound after weekly wound care at weeks 2 - 26
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Presence of confirmed venous, arterio-venous.
• Patients age over 18 years and under age of 90 years.
• Ulcer duration over 12 weeks and less than 5 years consecutively
• <15% ulcer size reduction in 4 weeks prior to inclusion
• Ulcer is between 1-40 cm2 in size
• ABPI ≥ 0.7 and < 1.2
• Ulcer depth < 1 cm
• Mobile, at least able to walk with medical walker, and able to return for required treatments and study evaluations
• (Legally) capable to give informed consent
• Able to understand and comply with requirements of study protocol
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E.4 | Principal exclusion criteria |
• Ulcer chronicity < 12 weeks
• >15% increase of ulcer size in 4 weeks prior to inclusion or confirmed by historical data (patient status)
• Presence of deep vein trombosis or contra indication for compression therapy
• Severe co-morbidity reducing life expectance to < 1 year
• Use of oral corticosteroids and/or cytostatics >20 mg/per day;
• Allergies to Gentamycin (which is used in the tissue media), Clindamycin or Ciprofloxacin, or the used local wound treatments
• Severe infection of ulcer, active cellulitis, osteomyelitis
• Expected non-compliance with compression therapy, protocol treatment or no informed consent
• Severe malnutrition
• Uncontrolled diabetes mellitus, HbA1c > 12% (108 mmol/mol)
• Anaemia Hb <6 mmol/l
• Current participation in another clinical trial, prior participation in another trial in 3 months.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. End of study at 26 weeks after application of Tiscover or AS210
2. Wound closure
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Recurrence
o Number and percentage of recurred ulcers at 3 and 6 months after initial closure.
o Duration of closure.
• Quality of the healed skin
The quality of scarring will be assessed. The scars will be defined as atrophic, normotrophic or hypertrophic.
• Quality of life
Quality of life measured at baseline, when closed, and at 3 and 6 months follow
up. Quality of life will be assessed using
o SF36; Quality of life score
o VAS (visual analogue scale) for experienced pain.
• Take rate of individual Tiscover and AS210 patches.
o Number and percentage of Tiscover or AS210 patches present on the wound after weekly wound care at weeks 2 - 26
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. End of study at 26 weeks after application of Tiscover or AS210
2. Wound closure |
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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 | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
acellular dermal matrix (AS210) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
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
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The end of this trial is when the last patient (number 49) had his/her last visit at week 26 after application of Tiscover and follow up of 6 months after wound closure.
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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 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |