A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study in Healthy Male and Female Volunteers to Investigate the Safety, Tolerability, and Pharmacokinetics of Ascending Topical Doses of TCP-25 Applied to Epidermal Suction Blister Wounds and in Patients With Non-Healing Leg Ulcers and Patients With Dystrophic Epidermolysis Bullosa
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Xinnate AB
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
This is a three-part, Phase I, first-in-human study designed to evaluate the safety, tolerability, and potential systemic exposure of multiple topical doses of TCP-25. Part I includes healthy volunteers with acute epidermal wounds formed by the suction blister technique. Part II includes patients with non-healing leg ulcers and Part III patients with dystrophic epidermolysis bullosa (DEB).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to give written informed consent for participation in the study.
- •Healthy male or female subject 18-60 years (inclusive) of age at the time of signing the informed consent.
- •Body Mass Index (BMI) ≥ 18.0 and ≤ 30.0 kg/m
- •Healthy and intact skin where the blister suction wounds will be induced.
- •Women of childbearing potential (WOCBP) must have a documented negative serum pregnancy test done at the screening visit, within 4 weeks prior to suction blister formation and the start of study treatment.
- •WOCBP must practice abstinence (only allowed when this is the preferred and usual lifestyle of the subject) or must agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD] or intrauterine hormone-releasing system [IUS]) from at least 4 weeks prior to dose to 4 weeks after last dose. Female subjects must refrain from donating eggs from the date of dosing until 3 months after dosing with the IMP. Their male partner must agree to use a condom during the same time frame if he has not undergone vasectomy.
- •Women of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or females who have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle stimulating hormone [FSH] 25-140 IE/L is confirmatory).
- •Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of last dosing until 3 months after the last dosing with the IMP. Their female partner of child-bearing potential must use contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above).
- •Clinically relevant medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
排除标准
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- •Disease that may interfere with wound healing, e.g., diabetes type I/II, arterial-, renal-, liver, or cardiac insufficiency, chronic obstructive lung disease, cancer, autoimmune disease, edema at the study site, severe obesity, or previous known wound healing problems, as judged by the investigator.
- •Active skin disease, e.g., dermatitis, psoriasis and wounds, and/or tattoos in the areas where suction blister wounds will be induced, as judged by the investigator.
- •Any planned major surgery within the duration of the study.
- •After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:
- •Systolic blood pressure <90 or >160 mmHg, or
- •Diastolic blood pressure <50 or >100 mmHg, or
- •Pulse <40 or >90 beats per minute (bpm)
- •Any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
- •Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than three times per week is allowed before screening visit.
- •Female subjects who are pregnant or lactating or planning a pregnancy.
- •Systemic immunosuppressive treatment.
- •Subjects who are currently receiving or have received the following treatments within 2 weeks prior to screening are excluded from the study: - systemic corticosteroids or immunosuppressant agents; or - antibiotics via any route
- •Regular use of anticoagulants (i.e., heparin, warfarin, coumarins, other anticoagulants per Investigator's judgement) or non-steroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to the (first) administration of IMP, at the discretion of the Investigator.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to TCP-25 or to any excipients of the hydrogel.
- •Planned treatment or treatment with another investigational drug within 3 months prior to Day -
- •History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
- •Presence or history of drug abuse, as judged by the Investigator
- •Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening.
- •Involvement in the planning and/or conduct of the study.
- •Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.
- •Inclusion criteria:
- •Willing and able to give written informed consent for participation in the study.
- •Male patient, or female patient of non-childbearing potential, ≥40 years of age at the time of signing the informed consent.
- •Male subjects must be willing to use condom or be vasectomized or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of last dosing until 3 months after the last dosing with the IMP. Their female partner of child-bearing potential must use contraceptive methods with a failure rate of < 1% to prevent pregnancy.
- •Women of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or females who have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle stimulating hormone [FSH] 25-140 IU/L is confirmatory).
- •Clinically relevant medical history, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
- •Patients diagnosed with venous insufficiency by relevant physiological tests including doppler or venous plethysmography or diagnosed by relevant clinical evaluations.
- •Systolic index > 0.6 (Data from medical records from the last 2 years, or the assessment should be repeated at the screening visit).
- •Ulcer duration > 6 weeks
- •Total target ulcer area applicable for treatment: ≤ 30 cm2 (as measured with the Silhouette imaging equipment at the screening visit). (The target ulcer area may not consist of >2 separate ulcers.)
- •Ability to tolerate compression bandaging.
- •Willing to attend study site visits.
- •Exclusion criteria:
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- •Disease that may interfere with wound healing, e.g., diabetes type I/II, arterial-, renal-, liver, or cardiac insufficiency, chronic obstructive lung disease, cancer, autoimmune disease, edema at the study site, severe obesity, or previous known wound healing problems, as judged by the Investigator.
- •Active skin disease, e.g., dermatitis, psoriasis and wounds, and/or tattoos in the areas where suction blister wounds will be induced, as judged by the Investigator.
- •Any planned major surgery within the duration of the study.
- •After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:
- •Systolic blood pressure <90 or >160 mmHg, or
- •Diastolic blood pressure <50 or >100 mmHg, or
- •Pulse <40 or >90 beats per minute (bpm)
- •Any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
- •Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than three times per week is allowed before screening visit.
- •Female subjects who are pregnant or lactating or planning a pregnancy.
- •Systemic immunosuppressive treatment.
- •Subjects who are currently receiving or have received the following treatments within 2 weeks prior to screening are excluded from the study:
- •systemic corticosteroids or immunosuppressant agents; or
- •antibiotics via any route
- •Regular use of anticoagulants (i.e., heparin, warfarin, coumarins, other anticoagulants per Investigator's judgement) or non-steroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to the (first) administration of IMP, at the discretion of the Investigator.
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研究组 & 干预措施
Dose group 3
0.15 mL of TCP-25 gel (8.6 mg/mL) or 0.15 mL placebo gel per wound applied as topical treatment on days 1, 2, 3, 5, and 8
干预措施: TCP-25 gel 8.6 mg/ml or placebo gel (Drug)
Dose group 1
0.15 mL of TCP-25 gel (0.86 mg/mL) or 0.15 mL placebo gel per wound applied as topical treatment on days 1, 2, 3, 5, and 8
干预措施: TCP-25 gel 0.86 mg/ml or placebo gel (Drug)
Dose group 2
0.15 mL of TCP-25 gel (2.9 mg/mL) or 0.15 mL placebo gel per wound applied as topical treatment on days 1, 2, 3, 5, and 8
干预措施: TCP-25 gel 2.9 mg/ml or placebo gel (Drug)
结局指标
主要结局
Adverse Events
时间窗: 15 days in Part I (modified endpoints & timeframes in Part II & III)
Frequency, intensity and seriousness of adverse events (AEs)
Number of patients with clinically significant changes from baseline in electrocardiogram (ECG)
时间窗: During screening (baseline) and on day 11 in Part I (modified endpoints & timeframes in Part II & III)
Systolic and diastolic blood pressure and pulse will be measured. Any abnormalities will be specified and documented as clinically significant or not clinically significant by the investigator.
Number of patients with clinically significant changes from baseline in physical examinations
时间窗: During screening (baseline) and on day 11 in Part I (modified endpoints & timeframes in Part II & III)
A physical examination will include assessments of general condition, lymph nodes, throat, heart, lungs and abdomen. Any abnormalities will be specified and documented as clinically significant or not clinically significant by the investigator.
Incidence of abnormal local reactions (Local tolerability)
时间窗: Day 15 in Part I (modified endpoints & timeframes in Part II & III)
Incidence of abnormal local reactions as compared to expected wound healing outcome, by direct assessment by Investigator: * Skin and wound erythema (abnormal reaction noted) * Skin and wound oedema and swelling (abnormal reaction noted) * Wound necrosis, crusting, and hemorrhage (abnormal reactions noted) * Wound purulent discharge as sign of excessive bacterial colonization and/or infection
Number of patients with clinically significant changes from baseline in safety laboratory parameters
时间窗: During screening (baseline) and on day 11 in Part I (modified endpoints & timeframes in Part II & III)
Safety laboratory parameters include haematology, clinical chemistry and coagulation. Any lab values outside the normal ranges will be judged as not clinically significant or clinically significant by the investigator. Haematology parameters to be measured are: * Haematocrit * Haemoglobin * Erythrocytes * Mean corpuscular volume * Mean corpuscular haemoglobin * Mean corpuscular haemoglobin concentration * Thrombocytes * Leukocytes * Eosinophils * Neutrophils * Basophils * Lymphocytes * Monocytes Clinical chemistry parameters to be measured are: * Alanine aminotransferase (ALT) * Aspartate aminotransferase (AST) * Creatinine * C-reactive protein (CRP) * Glucose * Haemoglobin A1c (HbA1C) Coagulation parameters to be measured are: * Activated partial thromboplastin time (APTT) * Prothrombin complex/International Normalised Ratio (PK/INR)
Number of patients with clinically significant changes from baseline in vital signs.
时间窗: During screening (baseline) and on day 11 in Part I (modified endpoints & timeframes in Part II & III)
Vital signs include systolic/diastolic blood pressure and pulse rate. Any vital signs outside the normal ranges will be judged as not clinically significant or clinically significant by the investigator.
次要结局
- Plasma concentration of TCP-25(Day 5 (measured before administration of intervention) in Part I (modified endpoints & timeframes in Part II & III))