YQ23 Study in Patients With Critical Limb Ischaemia

NCT04792008 | Terminated Phase 1 DMC

• 1 other identifier: YQ23-19001
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

This is an early phase study to assess how safe and tolerable is the new study drug YQ23 and to compare the effectiveness of YQ23 against normal saline to treat critical limb ischaemia. The study also aims to understand how it affects the body and an optional substudy to assess how the human body takes up, breaks down, and clears the study drug. Eligible patients will be randomised to have a 2:1 chance to receive a single, intravenous, fixed dose of YQ23 or normal saline. Neither the patient nor the study site will know which treatment has been given. On the day of YQ23 administration, patients will be asked to stay in the study site for 3 days for safety observation. After discharge, they will be required to visit the study clinic for 3 times in a year to continue safety monitoring and assessment of treatment effect. Each subject's participation will be about 13 months after signing the informed consent.

Conditions

Critical Limb Ischemia

Outcome Measures

Primary Outcomes (6)

• Safety and tolerability of single IV dose of YQ23 - adverse and serious adverse events

  Incidence of adverse events and serious adverse events

  From the time of signing informed consent through study completion, a duration of 13 months.

• Safety and tolerability of single IV dose of YQ23 - abnormal laboratory values

  Number of participants with a change in laboratory values of haematology, chemistry or urinalysis which is of clinical significance

  From the time of signing informed consent through study completion, a duration of 13 months.

• Safety and tolerability of single IV dose of YQ23 - 12 lead electrocardiogram (ECG)

  Number of participants with a change in 12-lead ECG measurements which is of clinical significance

  From the time of signing informed consent through study completion, a duration of 13 months.

• Safety and tolerability of single IV dose of YQ23 - vital signs

  Number of participants with a change in vital signs of blood pressure, pulse rate, respiratory rate or oral temperature which is of clinical significance

  From the time of signing informed consent through study completion, a duration of 13 months.

• Safety and tolerability of single IV dose of YQ23 - physical examinations

  Number of participants with a change in physical examination findings which is of clinical significance

  From the time of signing informed consent through study completion, a duration of 13 months.

• Safety and tolerability of single IV dose of YQ23 - major adverse limb events (MALE)

  The incidence of MALE of interest. MALE include amputation (transtibial or above) or any major vascular intervention in the index limb

  From pre-dose to Month 1

Secondary Outcomes (20)

• Efficacy of single dose YQ23 as compared to placebo - all cause mortality

  From the time of signing informed consent to Month 12

• Efficacy of single dose YQ23 as compared to placebo - amputation free survival

  From pre-dose to Month 12

• Efficacy of single dose YQ23 as compared to placebo - MALE of interest

  At month 6 and 12

• Efficacy of single dose YQ23 as compared to placebo - Rutherford classification

  From pre-dose, Month 1, 6 and 12

• Efficacy of single dose YQ23 as compared to placebo - visual analogue pain scale

  From pre-dose, Month 1, 6 and 12

Study Arms (2)

YQ23 Single dose

EXPERIMENTAL

Two-third of randomized patients will receive YQ23 as active treatment

Biological: YQ23

Placebo Single dose

PLACEBO COMPARATOR

One-third of randomized patients will receive matching placebo

Biological: Matching placebo

Interventions

YQ23 BIOLOGICAL

Single dose of 120 mg/kg YQ23 via intravenous route will be evaluated

YQ23 Single dose

Matching placebo BIOLOGICAL

Single dose of 0.9% normal saline via intravenous route as matching placebo

Placebo Single dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CLI (Rutherford Classification stage 4, 5 or 6) including at least one of the following:
• resting ankle systolic pressure (either dorsalis pedis or posterior tibial artery) \<=70 mmHg in affected limb
• resting toe systolic pressure \<=50 mmHg in affected limb
• TcPO2 \<=30 mmHg
• One of the following clinical presentations:
• pain at rest
• ischaemic ulcer, and/or focal gangrene for at least 2 weeks
• Diagnosis of severe lower extremity peripheral artery occlusive disease as evidenced by either:
• Documented significant stenosis (\>=75%) of \>=1 of the following arteries: superficial femoral, popliteal, and infra-popliteal arteries, as assessed by imaging test, or
• 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
• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• New Beta Innovation Limited: lead

Study Sites (2)

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Study Officials

• Billy Lau

  New Beta Innovation Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 10, 2021
• Study Start: March 10, 2021
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: December 8, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

HK (2)