A Research Study to Evaluate the Safety and Potential Efficacy of ON101 Cream for the Treatment of Venous Leg Ulcers.

Study Overview
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Brief Summary
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A Research Study to evaluate the safety and potential efficacy of ON101 cream for the treatment of venous leg ulcers.The objectives of the study are to determine the safety and to explore the potential efficacy of ON101 cream in patients with venous leg ulcers.

Detailed Description
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This is a multi-center, open-label study to investigate the Safety and Potential Efficacy of ON101 Cream in Venous Leg Ulcers (VLU) patients. Subjects with VLU of CEAP C6 (active venous ulcer) or C6R (recurrent active venous ulcer) are to be included in this study. If a subject has more than one ulcer on the leg, the most severe ulcer then the largest ulcer that confirm to meet the eligibility criteria will be selected for study evaluation. 12 eligible subjects will be enrolled and receive ON101 cream treatment. Enrolled subjects will be instructed to apply the study treatment on the selected target ulcer for a maximum of 18 weeks, until the ulcer complete closure (ulcer size of 0) for two consecutive visits that at least 2 weeks apart, or until the subject exit the study prematurely due to any reason. Identical standard of care (SoC) procedure will be performed in both the control and investigational product arms throughout the study period, which including ulcer cleansing, debridement if necessary, and application of a suitable dressing and compression system until complete ulcer closure. Subjects are required to apply compression device at least 8 hours per day throughout the treatment period. The study consists of three periods, a 2-week Screening/Run-in period, an up-to-18-week Treatment period, and a 1-to-2-week Follow-up period. The Screening/Run-in period is to ensure the subjects' eligibility and their compliance to compression therapy and to exclude subjects who demonstrate substantial healing resulting solely from improved compliance with SoC. The Treatment period is to determine the safety and to explore the potential efficacy of the study product. The Follow-up period is to assess the safety. During the Follow-up period, SoC will be provided to subjects with non-healing or recurrent target ulcer.

Official Title
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A Research Study to Evaluate the Safety and Potential Efficacy of ON101 Cream for the Treatment of Venous Leg Ulcers.

Conditions
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Venous Leg Ulcers (VLU)

Intervention / Treatment
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* Drug: ON101 Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed a written informed consent prior to the study procedure Male or female aged at least 20 years old Venous outflow/venous capacitance (VO/VC) compatible with venous insufficiency measured at screening visit or within 3 months prior to enrollment Has adequate vascular perfusion of the affected limb, confirmed by Ankle-Brachial Index (ABI) ≥ 0.8 and ≤ 1.3 measured at screening visit or within 3 months prior to enrollment The target ulcer have all of the following characteristics: C6 or C6R per the Clinical-Etiology-Anatomic-Pathophysiologic (CEAP) Classification System; Located between the knee and ankle (at or above the malleolus); No active infection; Post debridement ulcer area is ≥ 3 cm2 and ≤ 20 cm2 at the time of enrollment; Has been presented for at least 6 weeks before enrollment; A minimum of 2 cm margin between the qualified target ulcer and any other ulcers on the target limb (post debridement); Involves a full thickness skin loss, but without exposure of tendon, muscle, or bone; Must be nonhealing as defined as ≤ 30% reduction in ulcer area in response to standard of care (SoC) during the 2-week run-in period Considered by the Investigator to be compliant/adhere to the compression device during the 2-week run-in period If female of child-bearing potential, has a negative pregnancy test on urine at screening and must not be breastfeeding Able and willing to attend the scheduled visits and comply with the study procedures. Exclusion Criteria: Presence of necrosis, purulence, or sinus tracts that cannot be removed by debridement With deep vein thrombosis within 4 weeks prior to enrollment Has endovenous surgery planned or performed within 4 weeks prior to enrollment Laboratory values at Screening of: Liver function test (total bilirubin, aspartate aminotransferase [AST], or alanine aminotransferase [ALT]) > 3x the upper limit of normal, or Poor nutritional status defined as albumin < 2.5 g/dL, or Renal function test (serum creatinine) > 2x the upper limit of normal, or Glycosylated hemoglobin (HbA1c) ≥ 9 % Presence of any clinically significant medical condition(s) in medical history during screening period that, in the opinion of the Investigator, could interfere with ulcer healing, including but not limited to the following: Systemic infection not controlled by suitable antibiotic treatment Active malignant disease. A subject, who has had a malignant disease in the past, was treated and is currently disease-free, maybe considered for study entry. Acquired immune deficiency syndrome (AIDS) or HIV positive Has received treatment with immunosuppressive or chemotherapeutic agents, radiotherapy, or systemic corticosteroids within 4 weeks prior to enrollment Heavy smoker (≥ 20 cigarettes per day) Use of any investigational drug or therapy within 4 weeks prior to enrollment A psychiatric condition (e.g., suicidal ideation), current or chronic alcohol or drug abuse problem, determined from the subject's medical history, which in the opinion of the Investigator, may pose a threat to subject compliance Judged by the Investigator to be not suitable for study participation

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: The study consists of 3 periods, a Screening/Run-in period, a treatment period, and a follow-up period.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ON101 Cream<br>Single arm of VLU group for ON101 Cream Test drug: Name: ON101 Dosage form: Topical cream Active ingredients: Extracts of Plectranthus amboinicus and Centella Asiatica Dose(s): Apply 1 cc per 5 cm2 ulcer size (not exceeding 2 mm in thickness) Dosing schedule: Apply once a day | Drug: ON101 Cream<br>* Test drug: Name: ON101 Dosage form: Topical cream Active ingredients: Extracts of Plectranthus amboinicus and Centella Asiatica Dose(s): Apply 1 cc per 5 cm2 ulcer size (not exceeding 2 mm in thickness) Dosing schedule: Apply once a day<br>* Other names: Fespixon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoint(1) : Treatment-Emergent Adverse Event | Incidence of treatment-emergent adverse event (TEAE); safety will be assessed by the incidence of adverse events, including overall AEs, AEs related to the ON101, study-ulcer-associated AEs and SAEs. | Through study completion, an average of 6 months | 
| Safety endpoint(2-1) : Change from baseline in vital signs | Incidence of treatment-emergent adverse event (AE) Change from baseline in vital signs:pulse rate(times/min), SBP/DBP(mmHg), Body Temperature (°C), and respiratory rate ( breaths/min) | Through study completion, an average of 6 months | 
| Safety endpoint(2-2) : Change from baseline in physical examination | Incidence of treatment-emergent adverse event (AE) Change from baseline in the physical examination: HEENT (head, eyes, ears, nose, and throat), mouth, skin, neck (including thyroid), lymph nodes, spine, cardiovascular system, respiratory system, gastrointestinal system, nervous system, musculoskeletal system, blood and blood-forming organs and mental status. | Through study completion, an average of 6 months | 
| Safety endpoint(2-3) : Change from baseline in laboratory test | Incidence of treatment-emergent adverse event (AE) Change from baseline in laboratory tests: Complete blood count (WBC, Neutrophils, Monocytes, Hb, MCV, MCH, MCHC, Platelet), Biochemistry (HbA1c, fasting blood glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total bilirubin, aspartate aminotransferase, alanine aminotransferase, creatinine, albumin), and Urinalysis (pH, protein, glucose, ketone, blood, urobilinogen, bilirubin, nitrite, leukocyte) | Through study completion, an average of 6 months | 
| Safety endpoint(3) : Target ulcer infection | Incidence of target ulcer infection | Through study completion, an average of 6 months | 
| Safety Analysis through the descriptive statistics | Treatment-emergent adverse events will be analyzed mainly with descriptive statistics. The frequency, percentage of subjects, severity, and the relationship with study drug of adverse events will be listed. The continuous variables (e.g., vital signs and laboratory value) will be described using the number of observation, mean, standard deviation, median, range (min, max), and 95% confidence interval. Other categorical variables (e.g., physical examination) will be described using frequencies and proportion or the frequency of normality/abnormality. TEAEs will be coded using MedDRA (version 23.1 or later) and grouped by system organ class and preferred term and events. | Through study completion, an average of 1 year for the final review. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy endpoint(1): ulcer healing time measured | Time to complete ulcer healing:measured by the photo to ensure the target ulcer area, such as length, width,and depth changed | Through study completion, an average of 6 months | 
| Efficacy endpoint(2): complete healing of the target ulcer | Incidence of complete healing of the target ulcer:measured by the photo to ensure the target ulcer area, such as length, width,and depth changed. | Through study completion, an average of 6 months | 
| Efficacy endpoint(3): change from baseline in the target ulcer area | Mean change from baseline in the target ulcer area:measured by the photo to ensure the target ulcer area, such as length, width,and depth changed. | Through study completion, an average of 6 months | 
| Efficacy endpoint(4): percentage change from baseline in the target ulcer area | Percentage change from baseline in the target ulcer area:measured by the photo to ensure the target ulcer area, such as length, width,and depth changed | Through study completion, an average of 6 months | 
| Efficacy endpoint(5): between target ulcer area and time to complete ulcer healing | Correlation between target ulcer area and time to complete ulcer healing:measured by the photo to ensure the target ulcer area, such as length, width,and depth changed | Through study completion, an average of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ON101, Fespixon, Venous leg ulcers, C6 or C6R