A Prospective Randomized Double-Blinded Placebo Controlled, Explorative Phase I Trial to Investigate the Safety and Tolerability of Two Different Doses of Topically Administered APOSEC™ in Healthy Male Subjects With Artificial Dermal Wounds

NCT ID: NCT02284360

Last Updated: 2015-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2015-06-30

Brief Summary

This is a prospective, single center, randomized, double-blinded, placebo-controlled, exploratory phase I clinical trial in healthy male subjects to investigate the safety and tolerability of the cytokine based gel APOSEC™. The proof of safety and tolerability of APOSEC™ is the primary objective. The secondary objective is to measure the extent of wound healing of APOSEC™.

Detailed Description

APOSEC™ is a human product derived from lyophilized conditional medium of peripheral blood mononuclear cells (PBMC) following 24 hours cultivation after irradiation with 60Gy. The soluble factors produced by these factors (secretome) have regenerative functions and enhance wound healing due to the activation of signaling cascades involved in the cell migration, proliferation and cell survival. The product also possesses strong angiogenic properties as well in vivo and in vitro. APOSEC™ is intended for topical use only, to promote healing of wounds in association with standard wound care. Standard wound care includes initial debridement, avoidance and treatment of wound related infections and a non-weight-bearing regime to decrease the pressure on the wound.

The verum APOSEC™ is processed as lyophilisate and resuspended in Nugel for the final formulation. It will be compared with a placebo, a cell-free parallel produced cell-free control lyophilisate that is finally formulated in Nugel as well.

10 eligible healthy volunteers will consecutively be allocated to 2 different dose groups of APOSEC™ in a dose escalation scheme. The first 5 subjects in group A receive the low dose of APOSEC™ (12.5*10^6 lyophilized PBMC/mL), the subsequent 5 subjects in group B will receive the high dose of APOSEC™ (25*10^6 lyophilized PBMC/mL). Each volunteer will receive both Verum and Placebo on two artificial wounds on the inner upper non-dominant arm. The location of application of the Verum and Placebo (proximal or distal) is subjected to randomization.

Conditions

Healthy; Artificial Dermal Wound

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: DOUBLE

Study Groups

Group A: Low dose

Each volunteer in group A will receive both Verum and Placebo.

The Verum lyophilized APOSEC™ is derived from 12.5*10^6 cells/ml irradiated lyophilized PBMC. The lyophilizate will be resuspended in 0.9% 200 µL NaCl and finally formulated in 800 µL Nugel.

As Placebo a cell-free control lyophilisate resuspended in 0.9% 200 µL NaCl and finally formulated with 800 µL Nugel is used. The location of application on the inner upper arm (proximal or distal) of Verum and Placebo will be randomized.

Group Type: EXPERIMENTAL

APOSEC™ for cutaneous use

Intervention Type: DRUG

On day 0, a blinded and randomized test treatment with Verum and Placebo is performed on intact skin. If the subject does not reveal any adverse events, the actual treatment phase is initiated 24h later.

Following baseline evaluation on day 1, two punch biopsies (4mm) on the inner upper side of the non-dominant arm are set under local anesthesia. One wound on the upper arm (proximal or distal) will be treated with placebo and the second wound will be treated with the allocated concentration of Verum according to previous randomization scheme set for test treatment. Approximately 1ml of Verum vs. placebo will be applied on the artificial wounds.

From day 2 to 6, artificial wounds will be cleaned with 0.9 % NaCl and then allocated treatment will be administered. Wound dressing will be done daily and will cover the whole area of application.

On day 7 the treatment is terminated and the wound is evaluated with respect the extension of wound closure.

Group B: High dose

Each volunteer in group B will receive both Verum and Placebo.

The Verum lyophilized APOSEC™ is derived from 25*10^6 cells/ml irradiated lyophilized PBMC. The lyophilizate will be resuspended in 0.9% 200 µL NaCl and finally formulated in 800 µL Nugel.

As Placebo a cell-free control lyophilisate resuspended in 0.9% 200 µL NaCl and finally formulated with 800 µL Nugel is used. The location of application on the inner upper arm (proximal or distal) of Verum and Placebo will be randomized.

Group Type: EXPERIMENTAL

APOSEC™ for cutaneous use

Intervention Type: DRUG

On day 0, a blinded and randomized test treatment with Verum and Placebo is performed on intact skin. If the subject does not reveal any adverse events, the actual treatment phase is initiated 24h later.

Following baseline evaluation on day 1, two punch biopsies (4mm) on the inner upper side of the non-dominant arm are set under local anesthesia. One wound on the upper arm (proximal or distal) will be treated with placebo and the second wound will be treated with the allocated concentration of Verum according to previous randomization scheme set for test treatment. Approximately 1ml of Verum vs. placebo will be applied on the artificial wounds.

From day 2 to 6, artificial wounds will be cleaned with 0.9 % NaCl and then allocated treatment will be administered. Wound dressing will be done daily and will cover the whole area of application.

On day 7 the treatment is terminated and the wound is evaluated with respect the extension of wound closure.

Interventions

APOSEC™ for cutaneous use

On day 0, a blinded and randomized test treatment with Verum and Placebo is performed on intact skin. If the subject does not reveal any adverse events, the actual treatment phase is initiated 24h later.

Following baseline evaluation on day 1, two punch biopsies (4mm) on the inner upper side of the non-dominant arm are set under local anesthesia. One wound on the upper arm (proximal or distal) will be treated with placebo and the second wound will be treated with the allocated concentration of Verum according to previous randomization scheme set for test treatment. Approximately 1ml of Verum vs. placebo will be applied on the artificial wounds.

From day 2 to 6, artificial wounds will be cleaned with 0.9 % NaCl and then allocated treatment will be administered. Wound dressing will be done daily and will cover the whole area of application.

On day 7 the treatment is terminated and the wound is evaluated with respect the extension of wound closure.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male subjects with 18-50 years of age at the day of inclusion
• Written informed consent will be obtained prior to screening examination
• BMI of 19-27 (extremes included)
• Subjects are in good clinical and mental health as established by medical history, physical examination, vital signs, electrocardiogram, results of biochemistry, hematology, virology and urine analysis at the Screening Visit

Exclusion Criteria

• Lack of willingness or capacity to co-operate appropriately
• Regular use of medications
• History of malignancies
• History of wound healing abnormalities
• Chronic dermatological disease
• History of chronic autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, diabetes mellitus, Lupus erythematodus
• Tattoos in the region of planned punch biopsy
• Positive HIV serology or evidence of active hepatitis
• Allergy requiring medical treatment within 4 weeks before study initiation
• Active infection of fever > 38°C within 7 days prior randomisation
• Blood donation within 4 weeks before study initiation
• Clinically relevant abnormalities in the laboratory testing, vital signs, ECG or physical examination
• Participation in another clinical trial with an investigational day within 4 weeks before study participation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Michael Wolzt

Univ.-Prof. Dr.med.univ. Michael Wolzt

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medical University of Vienna, Department of Clinical Pharmacology

Vienna, Vienna, Austria

Countries

Austria

Other Identifiers

MarsyasI

Identifier Type: -

Identifier Source: org_study_id