| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| TCP-25 gel targets both bacteria and inflammation, aspects common to many wounds and is being developed for a range of wound healing indications including prevention and treatment of infection and inflammation in XYZ and in other acute or non-healing wounds. |
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| E.1.1.1 | Medical condition in easily understood language |
| Treatment is to be given to patients with XYZ to promote wound healing. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part 1: The primary objective is to evaluate the safety and tolerability of three dose levels of TCP-25 gel (0.86 mg/mL, 2.9 mg/ml and 8.6 mg/mL) applied topically to epidermal suction blister wounds.
Part 2: The primary objective is to evaluate the safety and tolerability of two doses of TCP-25 gel (2.9 mg/mL and 8.6 mg/mL) after applied topically to non-healing leg ulcers.
Part 3: The primary objective is to evaluate the safety and tolerability of up to four dose levels of TCP-25 applied by two strengths of TCP-25 gel (2.9 mg/mL and 8.6 mg/mL, respectively) topically to patients with
XYZ. |
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| E.2.2 | Secondary objectives of the trial |
Part 1: The secondary objective is to evaluate the systemic exposure of TCP-25 after applied topically to epidermal suction blister wounds.
Part 2: The secondary objective is to evaluate the systemic exposure of TCP-25 after applied topically to non-healing leg ulcers.
Part 3: The secondary objective is to evaluate the systemic exposure of TCP-25 when applied topically in up to four dose levels by two strengths of TCP-25 gel (2.9 mg/mL and 8.6 mg/mL) topically to patients with XYZ. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Part 1
1.Willing and able to give written informed consent for participation in the study
2.Healthy male or female subject 18-60 years (inclusive) of age at the time of signing the informed consent.
3.Body Mass Index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2
4.Healthy and intact skin where the blister suction wounds will be induced
5.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 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. 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
6.Clinically relevant medical history, physical findings,vital signs,ECG and laboratory values at the time of screening, as judged by the Investigator
Part 2:
1.Willing and able to give written informed consent for participation in the study
2.Male patient, or female patient of non-childbearing potential, ≥40 years of age at the time of signing the informed consent.
3.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.
4.Clinically relevant medical history,vital signs,ECG and laboratory values at the time of screening, as judged by the Investigator.
5.Patients diagnosed with venous insufficiency by relevant physiological tests including doppler or venous plethysmography or diagnosed by relevant clinical evaluations.
6.Systolic index > 0.6 (Data from medical records from the last 2 years, or the assessment should be repeated at the screening visit)
7.Ulcer duration > 6 weeks
8.Total target ulcer area applicable for treatment: ≥ 40 and ≤ 120 cm2 (as measured with the Silhouette imaging equipment at the screening visit). (The target ulcer area may not consist of >2 separate ulcers)
9.Ability to tolerate compression bandaging
10.Willing to attend study site visits
Part 3
1.Willing and able to give written informed consent for participation in the study.For 15 to 17-year-olds: A separate consent is required from both (if applicable) the patient’s parents/legal guardians
2.Male patient,or female patient of non-childbearing potential with documented diagnosis of inherited XYZ, ≥15 years of age at the time of signing the informed consent.
3.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
4.Clinically relevant medical history at the time of screening, as judged by the Investigator
5.Presence of two target wound areas of 50 cm2.The primary wound area should not be located at anatomical sites with high likelihood of accidental trauma (e.g., knee, elbow).The secondary wound area could be located at anatomical sites with high likelihood of accidental trauma or be within the higher age span. Both wound areas should meet all the following characteristics:
a.Including open wound with a surface area of ≤ 30 cm2 (as measured with the Silhouette imaging equipment at the screening visit).
b.At Visit 2 (first IMP treatment), each target wound should not present a surface reduction ≥ 30 % from the Screening visit
c.Wound aged ≥ 3 weeks to < 9 months at the Screening visit
6.Presence of a reference wound area of 50 cm2 to be treated with standard of care only and to be included in the exploratory assessment. The wound area should match the primary wound area for following characteristics:
a.Including open wound with a surface area of ≤30 cm2 (as measured with the Silhouette imaging equipment at the screening visit).
b.At Visit 2 (first IMP treatment), the wound should not present a surface reduction ≥ 30 % from the Screening visit
c.Wound aged ≥3 weeks to <9 months at the Screening visit
d.Not located at anatomical sites with high likelihood of accidental trauma (e.g., knee, elbow)
7.Willing to attend study site visits
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| E.4 | Principal exclusion criteria |
Part 1:
1.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.
2.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.
3.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.
4.Any planned major surgery within the duration of the study.
5.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)
6.Any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
7.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.
8.Female subjects who are pregnant or lactating or planning a pregnancy.
9.Systemic immunosuppressive treatment.
10.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
11.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.
12.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.
14.History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
15.Presence or history of drug abuse, as judged by the Investigator
Part 2:
1.Presence or documented illness, which in the Investigator’s opinion may negatively affect wound healing or interfere with the study conduct.
2.Target wound present for more than 5 years.
3.Clinical signs of infection in or around the wound in need of antibiotic treatment.
4.Albumin <25 g/L or capillary Hb <90 g/L, or HbA1c > 70 mmol/mol at the time of the screening visit.
5.Any planned major surgery within the duration of the study.
6.Patients who are currently receiving or have received the following treatments within 2 weeks prior to screening are excluded from the study:
- systemic corticosteroids above 5 mg prednisolone or equivalent, or
- immunosuppressant agents; or
- antibiotics via any route.
7.Regular use of anticoagulants (i.e., heparin, warfarin, coumarins, other anticoagulants affecting APTT and/or PK/INR per Investigator’s judgement) within 2 weeks prior to the (first) administration of IMP, at the discretion of the Investigator.
8.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.
Part 3
1.Any subtype of XYZ other than XYZ.
2.XYZ index wounds that have infection in need of systemic antibiotic treatment.
3.Presence of or documented illness, which in the Investigator’s opinion may negatively affect wound healing or interfere with the study conduct.
4.Subject has evidence of a systemic infection or has used systemic antibiotics for XYZ-related infections within 7 days before the screening visit (Visit 1).
5.Administration of systemic corticosteroids within 30 days (> 10 mg daily of prednisolone or corresponding) or of topical corticosteroids on target wound areas (primary, secondary and reference wound areas) within 14 days before the screening visit (Visit 1). Corticosteroids for inhalation, ophthalmic, or intranasal use are permitted.
6.Subject has undergone stem cell transplant or gene therapy for the treatment of XYZ with an effect on target wounds.
7.History of malignancy, including basal cell carcinomas or squamous cell carcinomas in the wound areas that will be included in the study.
8.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.
9.Planned treatment or treatment with another investigational drug within 3 months prior to Day -1.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1 and 2:
•Frequency, intensity and seriousness of adverse events (AEs).
•Local tolerability: 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.
•Clinically significant changes from baseline in electrocardiogram (ECG), vital signs (systolic/diastolic blood pressure, pulse rate), safety laboratory parameters (haematology, clinical chemistry and coagulation) and physical examinations.
Part 3
• Frequency, intensity and seriousness of adverse events (AEs).
• Local tolerability: Incidence of abnormal local reactions as compared to baseline , by direct assessment by Investigator :
- Peri-wound and open wound erythema of treated area (abnormal reaction noted)
- Peri-wound and open wound oedema and swelling of treated area (abnormal reaction noted)
- Peri-wound and open wound scaling of treated area (abnormal reaction noted)
- Peri-wound and open wound stinging/burning of treated area (abnormal reaction noted)
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Through-out the study period |
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| E.5.2 | Secondary end point(s) |
Part 1:
TCP-25 plasma concentrations as measured at Day 1, Day 2, Day 3 and Day 5.
Part 2:
TCP-25 plasma concentrations as measured at Day 8, 12, 15, 19, 22, 26 29 (optional), and 33 (optional).
Part 3:
TCP-25 plasma concentrations as measured at Day 22 |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Through-out the study period |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Part 1= controlled, randomised and double blind. Part 2 and 3 = open |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| The end of the study is defined as the date of the last visit of the last subject in the study. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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