Critical Limb Ischemia in Patients with Advanced Peripheral Arterial Occlusive Disease Subsequent to Percutaneous Transluminal Angioplasty MedDRA version: 14.1 Level: LLT Classification code 10066719 Term: Peripheral arterial occlusive disease aggravated System Organ Class: 100000004866
Conditions
Interventions
Product Name: MSC-Apceth
Product Code: NA
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: human autologous CD34-negative, bone-marrow derived mesenchymal stem cells
Other descriptiv
Sponsors
apceth GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult male or female patients between 40 to 80 years of age at the time of screening visit, 2. Patients with peripheral arterial occlusive disease (symptomatic PAOD), diagnosis of CLI defined as persistent, recurring ischemic rest pain for at least 2 weeks, and/or ulceration or gangrene of the foot or toe, with an ABPI = 0.5, 3. Patients with staging of =III according to Fontaine and =4 according to Rutherford categories, 4. Patients fulfilling the criteria for an invasive re-vascularisation procedure (PTA) at the discretion of the investigator, 5. Patients without major amputation of the lower extremities within the period of 6 months after inclusion in the opinion of the investigator, 6. Inclusion is only possible for • Patients of group A with bone marrow donation, who completed the questionnaire for bone marrow donation without abnormal findings; • Patients with adequate organ and bone marrow function as defined by the following laboratory parameters: Complete blood count/Reticulocytes Normal distribution Haemoglobin = 8 mmol/l Leucocytes = 3 x10E3/µL Thrombocytes = 100x10E3/µL Quick = 50% PTT 25-40 s Creatinine = 2.0 mg/dL Urea = 100 mg/dL gGT = 2,5 upper normal value GOT = 2,5 upper normal value GPT = 2,5 upper normal value Bilirubin = 2.0 mg/dL Alkaline phosphatase = 2,5 upper normal value CRP = 5,0 mg/dL • Patients with negative laboratory diagnostics for infections as summarised below: Parameter Specification HBs-Ag negative Anti-HBs negative, positive* Anti-HBc negative, positive* HBV-NAT negative Anti-HVC negative HCV-NAT negative Anti HIV 1/2 negative HIV NAT negative TPHA negative Anti-CMV-ELISA CMV pos (IgG+/IgM-); CMV neg (IgG-/IgM-). * if anti-HBc is positive, anti-HBs must be > 100 UI/l in adequate test and HBV-NAT negative • Patients without irregular antibodies [blood group antibodies - non-ABO (iso-)antibodies most commonly of the IgG type] in the diagnostics of blood group with Rhesus-factor and antibody status; • Patients with inconspicuous karyotyping results obtained for MSC-Apceth for Infusion final product. 7. Female patients of childbearing potential must have a negative urine pregnancy test recorded prior to the infusion of IMP, be non-lactating, and be willing to use adequate and highly effective method of contraception throughout the participation of the clinical trial, if sexually active. A highly effective method of birth control is defined as those which result in a low failure rate (i. e. less than 1% per year) when used consistently and correctly such as sterilization, implants, indictable, combines oral contracep-tives, some IUDs (hormonal), sexual abstinence or vasectomised partner. 8. Patients who are able to understand the requirements of the clinical trial, willing to provide voluntary writ
Exclusion criteria
Exclusion criteria: 1. Patients receiving systemic or direct target limb injection of antiangiogenic drugs, 2. Patients with concomitant wound treatments that include growth factors or tissue engineered products, 3. Patients with previous amputation of the talus, or above in the target limb, 4. Patients with wounds of a severity of greater than grade 2 on the Wagner Scale, 5. Patients with infection of the involved extremity(ies) manifest by fever, purulence and severe cellulites, 6. Patients with life-threatening ventricular arrhythmia, 7. Patients with unstable angina pectoris, 8. Patients with ST – segment elevation myocardial infarction and/or TIA/CVA within 6 months prior to enrolment, 9. Patients with severe congestive heart failure (i.e. NYHA Stage IV), 10. Patients with uncontrolled hypertension (defined as diastolic blood pressure >110 mmHg or systolic blood pressure >180 mmHg during screening), 11. Patients requiring uninterruptible anticoagulation that cannot be stopped for 24 hours prior to investigational treatment, 12. Patients with the diagnosis of end stage renal disease requiring dialysis (grade 5), 13. Patients with an uncontrolled diabetes mellitus (HbA1c > 9%), 14. Patients with any clinical sign of severe pulmonary disease and/or infection, uncontrolled lung disease including lung fibrosis, as defined by respiratory insufficiency or chest X-ray, 15. Patients with active hepatitis B-, or C- infection, or a positive test for HIV, or treponema pallidum (syphilis) at screening (refer to paragraph 6 in inclusion criteria), 16. Patients having any history of malignant tumour in the anamnesis or are currently on tumour treatment, 17. Patients with a documented history of active autoimmune disorders requiring systemic immunosuppressive therapy or an immunotherapy within 4 weeks prior to clinical trial enrolment (visit 1), 18. Patients with known allergies to protein products (e.g. porcine trypsin used in the cell production process) and X-ray contrast medication, 19. Patients with a history of severe alcohol or drug abuse within 3 months before screening in visit 1. 20. Patients who are pregnant or breast-feeding women or women of childbearing potential not protected by a highly effective contraceptive method of birth control, 21. Patients who are unsuitable for a MSC stem cell therapy in the opinion of the investigator, 22. Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s), 23. Patients unwilling or unable to comply with the clinical trial procedures, 24. Patients who are unwilling to consent to storage and saving and transmission of pseudonymous medical data for clinical trial reasons, 25. Patients who are legally incapacitated, 26. Patients who are legally detained in an official institute.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Evaluation of safety and tolerability of the treatment with MSC-Apceth for Infusion subsequent to PTA by collecting the safety parameters and adverse events in both treatment groups (PTA plus MSC-Apceth and PTA control group) during 12 months follow-up; ;Secondary Objective: 2. Comparison of the clinical course of therapy by the clinical parameters (PTA plus MSC-Apceth and PTA control group); 3. Comparison of the course of haemodynamic and vascular processes (PTA plus MSC-Apceth and PTA control group); ;Primary end point(s): 1. Evaluation safety and tolerability of the treatment with MSC-Apceth for Infusion subsequent to PTA by collecting the safety parameters described below and adverse events in both treatment groups during 12 months follow-up; 2. Comparison of the clinical course of therapy by clinical parameters; 3. Comparison of the course of haemodynamic and vascular processes ;Timepoint(s) of evaluation of this end point: over the course of the clinical trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): N/A;Timepoint(s) of evaluation of this end point: N/A | — |
Countries
Germany
Contacts
Public ContactClinical Trial Manager
apceth GmbH & Co. KG
Outcome results
None listed