YQ23 Study in Patients With Critical Limb Ischaemia (YAN)

This is an interventional treatment trial for Critical Limb Ischemia Read More

Inclusion Criteria:

• Diagnosis of CLI (Rutherford Classification stage 4, 5 or 6) including at least one of the following:

  1. resting ankle systolic pressure (either dorsalis pedis or posterior tibial artery) <=70 mmHg in affected limb
  2. resting toe systolic pressure <=50 mmHg in affected limb
  3. TcPO2 <=30 mmHg

• One of the following clinical presentations:

  1. pain at rest
  2. ischaemic ulcer, and/or focal gangrene for at least 2 weeks

• Diagnosis of severe lower extremity peripheral artery occlusive disease as evidenced by either:

  1. Documented significant stenosis (>=75%) of >=1 of the following arteries: superficial femoral, popliteal, and infra-popliteal arteries, as assessed by imaging test, or
  2. ABI <=0.80 or TBI <=0.60 of the index leg (in the event of non-compressible ankle arteries) for patients without a prior history of limb revascularization on the index leg, or an ABI <=0.85 or TBI <=0.65 of the index leg (in the event of non-compressible ankle arteries) for patients with a prior history of limb revascularization on the index leg.

• Contraceptive use

  1. Male patients and their female spouses/partners who are of childbearing potential must agree to use a high effective contraception consisting of two forms of birth control detailed in the protocol during the treatment period and for at least 6 days after the dose of the study treatment and refrain from donating sperm during this period
  2. A female patient is eligible if she is not pregnant, not breastfeeding, and at least on of the following conditions applies: (i) not a woman of childbearing potential (WOCBP), (ii) A WOCBP who agrees to follow the contraceptive guidance in the protocol during the treatment period and for at least 6 days after the dose of study treatment and refrain from donating ova during this period
• Patient is capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent and the protocol

Exclusion Criteria:

• Patients who have undergone successful revascularisation on the index leg within 4 weeks of the qualifying event
• Patients with estimated life expectancy <12 months
• Acute limb ischaemia due to thromboembolism within 2 weeks of the qualifying event
• Recent myocardial infarction within 30 calendar days prior to signing informed consent
• Recent stroke within 30 calendar days prior to signing informed consent
• Known history of severe congestive heart failure as determined through review of medical history
• Haemoglobin <8 g/dL, albumin <3 g/dL or other clinically significant abnormalities in the laboratory tests at screening
• Unwilling to complete follow-up evaluation
• Uncontrolled arterial hypertension with systolic blood pressure (SBP) >180 mmHg and/or diastolic blood pressure (DBP) >100 mmHg at screening
• Patients with history of long QT syndrome or whose QTc (calculated according to Bazett formula QTc = QT/ √RR) >470 ms at screening
• Patients with severe left ventricular dysfunction of <40% at screening
• Patients with clinically significant abnormalities in ECG parameters (other than QTc) or in the physical examination at screening that might comprise patient safety
• History of coagulopathy
• Patients having significant renal impairment with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 as determined by the 4-variable Modification of Diet in Renal Disease (MDRD) equation at Screening, except those patients who are on continuous ambulatory peritoneal dialysis(CAPD) or hemodialysis (HD)
• Significant liver impairment (abnormal Liver Function Tests >3 x upper limit of normal)
• Patients with active Hepatitis B infection (HBsAg positive and HBeAg positive) at screening
• Patient with a positive test for Hepatitis C virus antibody (anti-HCV) at screening
• Patient with known history of infection with human immunodeficiency virus (HIV) or any other active or chronic infection
• Patients with evidence of uncontrolled hypo- or hyperthyroidism
• History active malignancy (as determined through review of medical history), excluding local skin cancer (basal or squamous cell carcinoma)
• Patients unable to provide informed consent
• Known allergy to bovine products
• Receipt of bovine haemoglobin-based oxygen carrier (HBOC) or other HBOC in the past
• Use of an investigational drug or treatment within 12 months prior to signing informed consent; concurrent participation in any other investigational protocol
• Pregnancy and breastfeeding, as well as unwillingness to use effective methods contraception for women of childbearing potential