2024-517765-16-00招募中2 期
A RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, FIRST-IN-HUMAN, PHASE 1B/2A STUDY TO EVALUATE SAFETY AND EFFICACY OF SINGLE-DOSE TRI-001 IN PATIENTS WITH CHRONIC LIMB THREATENING ISCHEMIA (CLTI) DUE TO PERIPHERAL ARTERIAL DISEASE (PAD)
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 4
- 主要终点
- • The safety profile by assessing the occurrence of Adverse Events (AEs) and clinically significant changes in safety assessments (including vital signs, 12-lead electrocardiogram [ECG], safety laboratory testing [biochemistry, haematology, urinalysis], and other disease related safety measures) • Percentage change from baseline of the target wound size at Month 12
研究概览
简要总结
• Evaluate safety and tolerability of intramuscularly (i.m.) injected TRI 001 • Evaluate therapeutic effect of i.m. injected TRI 001 on target wound size
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female adult patient, not older than 85 years of age, who have signed an informed consent form either directly or through a legally authorised representative.
- •Objective evidence of CLTI due to PAD (Rutherford 5): a. Minor tissue loss, i.e., ischemic lesions must not have tendon or bone exposure (unless secondary to a minor amputation) b. Persistent, non-healing ischemic wound(s) which are: i. present during at least 2 weeks prior to screening, and ii. at least 1 wound with its surface area ≥3 cm
- •iii. likely irreversible wounds (e.g., non healing for >52 weeks) may be excluded at the discretion of the Investigator. excluded at the discretion of the Investigator. c. The index leg is meeting haemodynamic and metabolic criteria assessed in two consecutive examinations performed at least one week apart prior to randomisation (see Section 8.1.8): i. Resting ankle systolic pressure (ASP) <60 millimetre of mercury (mm Hg) in either the dorsalis pedis or posterior tibial arteries; or ii. Resting toe systolic pressure (TSP) <40 mm Hg; or iii. Transcutaneous oxygen pressure (TcPO2) <30 mm Hg. d. Sufficient inflow of aorta, iliac, common femoral artery and profunda assessed by doppler ultrasonography at screening. Definition sufficient inflow is in accordance with the IWGFD PAD Guidelines (Fitridge 2023). e. The patient has no promising conventional approach or is ineligible for revascularisation (including medical, endovascular, or surgical), as confirmed by the iAC (see Section 4.2). The following no-option conditions are considered eligible: i. Type I: patients with no sufficient perfused pedal vessels or with desert foot anatomy ii. Type II: patients with potential pedal target vessel but without suitable autologous or allogenic conduit bypass and no option for endovascular revascularisation iii. Type IV: patients with excessive or prohibitive risk for the revascularisation due to: • comorbidities (e.g., hypertension, coronary artery disease, renal failure, and pulmonary dysfunction) • having undergone failed endovascular surgeries (minimally 2 attempts) or failed open surgeries (minimally 1 attempt). These patients are considered eligible if the iAC deems these patients unsuitable for revascularisation attempts.
- •Patients with adequate organ function defined as following: a. Renal function: estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) equation (See Section 8.2.2) b. Hepatic function: i. Total bilirubin (TB) ≤1.5× upper limit of normal (ULN), and ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× ULN c. Bone marrow: i. Absolute neutrophil count ≥1.5× 109 cells/L ii. Haemoglobin ≥8.0 g/dL iii. Platelets ≥75× 109 cells/L
- •Currently taking an anti platelet agent (e.g., clopidogrel, ticlopidine, and aspirin etc.) for 2 weeks or more prior to randomisation as part of their standard of care, unless contraindicated or anti-coagulated
- •Patients of reproductive potential must agree to use an accepted and effective form of birth control methods during the study period. Contraceptive methods used by men or women should be consistent with Section 6.2.3 and local regulations.
- •Willing and able to complete all study assessments, follow study instructions and attend all study visits as required, in the opinion of the Investigator
排除标准
- •Presence of any significant disease/disorder (including lab/physical examination/ electrocardiogram (ECG)/medication abnormalities) which is unstable or uncontrolled despite treatment (e.g., aorto-iliac occlusion), or which in the opinion of the Investigator (and if deemed necessary with consultation of the medical monitor), may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject’s ability to participate in the study
- •Patients diagnosed with vasculitis.
- •Evidence of active systemic infection, including active infection with human immunodeficiency virus, hepatitis B or hepatitis C, as determined by hepatitis B surface antigen screening, detection of hepatitis C antibodies, or positive result of hepatitis C polymerase chain reaction analysis
- •Pulmonary disease requiring supplemental oxygen treatment on a daily basis
- •Patients with a severe comorbid disorder who are not expected to survive for more than 6 months in the opinion of the Investigator
- •Patients with ulcers from venous or neuropathic origin on the index leg
- •Patients currently receiving immunosuppressive, chemo or radiation therapy
- •Use of any investigational drug/device within 30 days or 5 half-lives of the investigational drug/device prior to Day 1, whichever is longer, or plans to participate in another study of a drug or device during the study period
- •Is a pregnant or breastfeeding female
- •No-option patients categorised as and confirmed by the iAC (see Section 4.2): a. Type III: Patients with tissue loss that expose vital structures (e.g., bones, tendons) precluding limb salvage of a functional foot. b. Type IV: Patients with a non-functional limb due to paralysis or chronic non-ambulatory status.
- •Evidence of active infection in the target wounds, classified as Wound, Ischemia, foot infection (WIfI) Infection Grade 3 and infected wounds requiring intravenous antibiotics. Diagnosis of osteolysis and osteomyelitis in foot Xray.
- •CLTI with an amputation proximal to a transmetatarsal level (Rutherford 6) in either leg
- •Stroke or acute myocardial infarction/unstable angina within 3 months before screening
- •Severe congestive heart failure symptoms according to New York Heart Association (NYHA) Stage IV
- •Uncontrolled diabetes mellitus (DM) type I or II with haemoglobin A1c (HbA1c) ≥10%
- •Planned major amputation within 4 weeks after randomisation
- •Active malignancy or history of a primary malignancy that has been diagnosed or required therapy within 2 years prior to the planned dose of study drug (exempt are: completely resected basal cell and squamous cell skin cancer, curatively treated localised prostate cancer, and completely resected carcinoma in situ of any site).
结局指标
主要结局
• The safety profile by assessing the occurrence of Adverse Events (AEs) and clinically significant changes in safety assessments (including vital signs, 12-lead electrocardiogram [ECG], safety laboratory testing [biochemistry, haematology, urinalysis], and other disease related safety measures) • Percentage change from baseline of the target wound size at Month 12
• The safety profile by assessing the occurrence of Adverse Events (AEs) and clinically significant changes in safety assessments (including vital signs, 12-lead electrocardiogram [ECG], safety laboratory testing [biochemistry, haematology, urinalysis], and other disease related safety measures) • Percentage change from baseline of the target wound size at Month 12
次要结局
- Key Secondary Endpoints: • Time to complete wound healing of the target wound* on the index leg • Change in rest pain score (Numeric Pain Rating Scale [NPRS], score 0-10) at Month 12 • Change in Vascular Quality of Life (VascuQoL)-6 score at Month 12 • Amputation Free Survival (AFS) of the index leg • Occurrence of Major Adverse Limb Event (MALE) of a vascular cause of the index leg • Occurrence of Major Adverse Cardiac Event (MACE)
- Important Secondary Endpoints: • Change in number of eligible wounds* present on the index leg at Month 12 • Change in haemodynamic and metabolic measurements of the index leg at Month 12 whenever it’s applicable: o Toe Brachial Index (TBI) o Ankle Brachial Index (ABI) o Transcutaneous oxygen pressure (TcPO2) • All-cause mortality
- Other Secondary Endpoints: • Occurrence of minor amputations of the index leg
研究者
Gilbert Wagener
Scientific
Ferring Ventures GmbH
研究点 (4)
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