Safety, Tolerability, and Pharmacokinetics of Ascending Topical Doses of TCP-25 Applied to Epidermal Suction Blister Wounds, Non-Healing Leg Ulcers and Patients With Dystrophic Epidermolysis Bullosa.

NCT05378997 | Completed Phase 1 DMC

• 2 other identifiers: TCP-25-0012021-004728-14
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Blister; Wound of Skin; Epidermolysis Bullosa; Varicose Ulcer of Lower Limb

Keywords

acute epidermal wounds; suction blister; healthy volunteers

Outcome Measures

Primary Outcomes (15)

• Adverse Events

  Frequency, intensity and seriousness of adverse events (AEs)

  15 days in Part I (modified endpoints & timeframes in Part II & III)

• Incidence of abnormal local reactions (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

  Day 1 in Part I (modified endpoints & timeframes in Part II & III)

• Incidence of abnormal local reactions (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

  Day 2 in Part I (modified endpoints & timeframes in Part II & III)

• Incidence of abnormal local reactions (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

  Day 3 in Part I (modified endpoints & timeframes in Part II & III)

• Incidence of abnormal local reactions (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

  Day 5 in Part I (modified endpoints & timeframes in Part II & III)

• Incidence of abnormal local reactions (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

  Day 8 in Part I (modified endpoints & timeframes in Part II & III)

• Incidence of abnormal local reactions (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

  Day 11 in Part I (modified endpoints & timeframes in Part II & III)

• Incidence of abnormal local reactions (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

  Day 15 in Part I (modified endpoints & timeframes in Part II & III)

• Number of patients with clinically significant changes from baseline in electrocardiogram (ECG)

  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.

  During screening (baseline) and on day 11 in Part I (modified endpoints & timeframes in Part II & III)

• Number of patients with clinically significant changes from baseline in vital signs.

  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.

  During screening (baseline) and on day 11 in Part I (modified endpoints & timeframes in Part II & III)

• Number of patients with clinically significant changes from baseline in physical examinations

  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.

  During screening (baseline) and on day 11 in Part I (modified endpoints & timeframes in Part II & III)

• Number of patients with clinically significant changes from baseline in safety laboratory parameters

  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)

  During screening (baseline) and on day 2 in Part I (modified endpoints & timeframes in Part II & III)

• Number of patients with clinically significant changes from baseline in safety laboratory parameters

  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)

  During screening (baseline) and on day 3 in Part I (modified endpoints & timeframes in Part II & III)

• Number of patients with clinically significant changes from baseline in safety laboratory parameters

  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)

  During screening (baseline) and on day 5 in Part I (modified endpoints & timeframes in Part II & III)

• Number of patients with clinically significant changes from baseline in safety laboratory parameters

  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)

  During screening (baseline) and on day 11 in Part I (modified endpoints & timeframes in Part II & III)

Secondary Outcomes (4)

• Plasma concentration of TCP-25

  Day 1 (measured before blister formation) in Part I (modified endpoints & timeframes in Part II & III)

• Plasma concentration of TCP-25

  Day 2 (measured before administration of the intervention and 0.5 and 1 hours after administration of the intervention) in Part I (modified endpoints & timeframes in Part II & III)

• Plasma concentration of TCP-25

  Day 3 (measured before administration of the intervention 1 hour after administration of the intervention) in Part I (modified endpoints & timeframes in Part II & III)

• Plasma concentration of TCP-25

  Day 5 (measured before administration of intervention) in Part I (modified endpoints & timeframes in Part II & III)

Study Arms (3)

Dose group 1

EXPERIMENTAL

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

Drug: TCP-25 gel 0.86 mg/ml or placebo gel

Dose group 2

EXPERIMENTAL

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

Drug: TCP-25 gel 2.9 mg/ml or placebo gel

Dose group 3

EXPERIMENTAL

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

Drug: TCP-25 gel 8.6 mg/ml or placebo gel

Interventions

TCP-25 gel 0.86 mg/ml or placebo gel DRUG

TCP-25 gel (0.86 mg/mL) applied to two wounds per patient and placebo gel applied to two wounds per patient

Dose group 1

TCP-25 gel 2.9 mg/ml or placebo gel DRUG

TCP-25 gel (2.9 mg/mL) applied to two wounds per patient and placebo gel applied to two wounds per patient

Dose group 2

TCP-25 gel 8.6 mg/ml or placebo gel DRUG

TCP-25 gel (8.6 mg/mL) applied to two wounds per patient and placebo gel applied to two wounds per patient

Dose group 3

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/m2.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xinnate AB: lead
• Region Skane: collaborator

Study Sites (1)

Skåne University Hospital in Lund, Clinical Trial Unit

Lund, SE-221 85, Sweden

Location

Related Publications (2)

• Wallblom K, Forsberg F, Lundgren S, Fisher J, Cardoso J, Petruk G, Stromdahl AC, Saleh K, Puthia M, Schmidtchen A. Bactogram: Spatial Analysis of Bacterial Colonisation in Epidermal Wounds. Exp Dermatol. 2024 Dec;33(12):e70018. doi: 10.1111/exd.70018.

  PMID: 39627888 DERIVED

• Lundgren S, Wallblom K, Fisher J, Erdmann S, Schmidtchen A, Saleh K. Study protocol for a phase 1, randomised, double-blind, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics of ascending topical doses of TCP-25 applied to epidermal suction blister wounds in healthy male and female volunteers. BMJ Open. 2023 Feb 22;13(2):e064866. doi: 10.1136/bmjopen-2022-064866.

  PMID: 36813496 DERIVED

MeSH Terms

Conditions

Blister; Epidermolysis Bullosa

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part I: Multiple topical doses of TCP-25 will be administered in 3 sequential dose groups, each of 8 subjects. Within each cohort, the subjects will receive TCP-25 on one wound on each thigh and placebo on one wound on each thigh in a randomized fashion as topical treatment. In Part II: Multiple topical doses of TCP-25 will be administered to 6 patients with non-healing leg ulcers. In Part III: Up to 4 dose levels of TCP-25 will be administered in up to 5 patients with DEB by topical application of TCP-25 gel of two concentrations.

Study Record Dates

• First Submitted: April 25, 2022
• First Posted: May 18, 2022
• Study Start: April 7, 2022
• Primary Completion: March 16, 2024
• Study Completion: March 16, 2024
• Last Updated: March 26, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)