E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Critical Chronic lower limb ischemia |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic lower limb ischemia with resting pain or ischemic ulcers (critical ischemia) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058069 |
E.1.2 | Term | Critical limb ischemia |
E.1.2 | System Organ Class | 10047065 - Vascular 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 primary objective is safety of the AdVEGF-DdNdC gene therapy |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is efficacy of the AdVEGF-DdNdC gene therapy to improve limb blood flow and tissue recovery |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
informed consent signed, age over 60 years, chronic critical leg ischemia according to Rutherford and Fontaine classification (ischemic rest pain and regular requirement of analgesic and/or ischemic ulcer and/or toe gangrene) caused by severe PAOD, femoropopliteal or femorodistal surgical bypass is considered the most suitable treatment option as according to angiographic studies or MRA, palpable pulse in arteria femoralis communis in the operable leg, no prior proximal (thigh or femoral) amputation, stable pain or ischemic tissue lesion for at lest 2 weeks |
|
E.4 | Principal exclusion criteria |
patients with: acute limb ischemia, spreading leg infection, history or suspicion of malignant tumor, chronic immunosuppressive therapy, renal insuffiency (creatinin > 160 mg/l), NYHA 3-4 coronary artery disease, previous angiogenic growth factor / gene therapy, and patients that are not eligible for surgical bypass operation for any other reason |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety parameters (blood samples: clinical chemistry, transgene ELISA, thorax x-rays, clinical assessment) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
from screening upto 6 months (closing visit) |
|
E.5.2 | Secondary end point(s) |
Improved blood flow (contrast enhanced ultrasound, doppler ultrasound, MRI) and muscle energy metabolism (deoxy-myoglobin magnetic resonance spectroscopy and positron emission tomography) (if available) as well as limb salvage, healing of ischemic ulcers, subjective experience of ischemic rest pain, quality of life (Rand-36) and maximal walking distance |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
from screening upto 6 months (closing visit) |
|
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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
same IMP tested for a different disease (perviously myocardial ischemia) |
|
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |