Clinical trial NCT04945161: A Randomized,Double-blind,Placebo-controlled Clinical Study to Explore the Mechanism of Action of ON101 Cream in Patients With DFUs.
Official title: A Randomized, Double-blind, Placebo-controlled Clinical Study to Explore the Mechanism of Action (MOA) of ON101 Cream in Patients With Diabetic Foot Ulcers (DFUs).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetic Foot Ulcers
Lead sponsor: Oneness Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-06-30
Enrollment: 13
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blind, placebo-controlled clinical study to explore the mechanism of action (MOA) of ON101 cream in patients with diabetic foot ulcers (DFUs).The primary objective is to explore the mechanistic role of ON101 cream in healing diabetic foot ulcers by determining the molecular targets of ON101 cream.
Primary purpose: OTHER

Brief summary: The primary objective is to explore the mechanistic role of ON101 cream in healing diabetic foot ulcers by determining the molecular targets of ON101 cream.

Primary endpoint:

Percentage change from baseline in the expression level of individual target gene(s) at protein and/or mRNA level.

Secondary endpoints:

1. Comparison of the gene and/or protein expression level of individual target between ON101 and Placebo groups
2. Change from baseline in the wound microbiota composition in each group
3. Comparison of the wound microbiota composition between ON101 and Placebo groups
4. Comparison of the wound reduction rate in each group
5. Correlation of wound reduction rate with the alternated level of each target gene in each group.

Safety endpoints:

Incidence of treatment-emergent adverse event (AE) Change from baseline in vital signs, physical examination, and laboratory tests

Detailed description: This is a multicenter, randomized, double-blind, placebo-controlled study to explore the mechanism of action (MOA) of ON101 in treating chronic diabetic foot ulcers (DFUs). There will be 6 subjects ON101 treatment (Arm A) and 6 subjects in Placebo (Arm B) .

Twelve(12) eligible subjects with DFUs and are not undergoing dialysis will be enrolled and randomly assigned to receive either ON101 treatment (Arm A) or Placebo (Arm B) for six weeks. Treatment arm allocation will be done through randomization in a double-blind fashion. SoC will be provided throughout the study period.Subjects with DFUs not undergoing dialysis, N = 12 Arm A: ON101 plus SoC, N = 6 Arm B: Placebo plus SoC, N =6 SoC will be provided throughout the study period (from screening to end of treatment). SoC includes evaluation to ensure adequate arterial flow, wound cleaning, removal of necrotic, infected and/or nonviable tissue by debridement, maintenance of moist wound environment via regular changing of dressings, and management of infection through oral antibiotics, if necessary.

The study will have three periods, a Screening/Run-in Period, a Treatment Period, and a Safety Follow-up Period.

Screening/Run-in Period (14 days):

Treatment Period (up to 6 weeks ± allow window):

There will be five (5) visits during the Treatment Period. Baseline/V1 (Day 1 ± 3 days) Visit 2 to Visit 5/EOT (Day 14 to Day 42/EOT) Safety Follow-up Period (Day 49±1 or Day of EOT + 6-8 days)

Eligibility criteria: Inclusion Criteria:

1. Subjects, male or female, aged 20 to 80 years (inclusive) with Type 1 or Type 2 diabetes undergoing therapy for glycemic control.
2. Subjects has a glycosylated hemoglobin, HbA1c \< 12%.
3. Presence of at least one diabetic foot ulcer that meets all of the following criteria:

   1. At the time of Visit 0 (V0), the ulcer has existed for at least one month;
   2. At the time of Visit 1 (V1), the post-debridement ulcer presents Grade 2 or Grade 3 (without osteomyelitis or active infection) in Wagner Ulcer Classification System assessment; and
   3. Area should be ≥ 4 cm2 and ≤ 25 cm2;
   4. No higher than the ankle.
4. Subject has adequate vascular perfusion of the affected limb, confirmed by Ankle-Brachial Index (ABI) ≥ 0.8 and ≤ 1.3.
5. Clinically normal resting ECG at the first Screening Visit (V0) or, if abnormal, considered to be not clinically significant by the Investigator.
6. Subject must use an off-loading method for the target ulcer on the plantar during the whole study period.
7. Subject, if female of child-bearing potential, has a negative pregnancy test on urine at screening, must not be breastfeeding, and willing to use two medically accepted methods of contraception (e.g., barrier contraceptives \[female condom or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectables, combination oral contraceptives, transdermal patches, or contraceptives rings\], and intrauterine devices) during the course of the study (excluding women who are not of childbearing potential and/or who have been sterilized).
8. Subject is able and willing to comply with the study procedures.
9. A signed and dated informed consent form has been obtained from the subject.

Exclusion Criteria:

1. In response to standard of care (SoC), ulcer size reduction is ≥20% during the two-week run-in screening period (between the first Screening Visit/V0 and Baseline Visit/V1).
2. Ulcers with exposed bone or associated with osteomyelitis. Note: The osteomyelitis should be ruled out by clinical examination (probing of the wound) or X-ray findings where find necessary by the Investigator.
3. Presence of necrosis, purulence, or sinus tracts that cannot be removed by debridement.
4. Laboratory values at Screening of:

   1. Liver function test (total bilirubin, aspartate aminotransferase \[AST\], or alanine transaminase \[ALT\]) \> 3x the upper limit of normal, or
   2. Albumin \< 2.5 g/dL, or
   3. Renal function test (serum creatinine or urea) \> 2x the upper limit of normal
5. Presence of any clinically significant medical condition(s) in medical history during screening period that, in the opinion of the Investigator, could interfere with wound healing, including but not limited to the following:

   1. Acute or unstable Charcot foot
   2. Current sepsis
   3. 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.
   4. Acquired immune deficiency syndrome (AIDS) or HIV positive
6. Subject is currently receiving (i.e., within 30 days of randomization visit) or scheduled to receive any of the following medication or therapies, could interfere with wound healing during the course of the study:

   1. Immunosuppressive or chemotherapeutic agents, radiotherapy, or systemic corticosteroids
   2. Autoimmune disease therapy
   3. Lower limb revascularization surgery (e.g., angioplasty, artery bypass surgery)
   4. Hyperbaric oxygen therapy
   5. Bioengineered tissue or skin substitutes
   6. Use of any investigational drug(s)
   7. Cell therapy
7. More than two (2) ulcers located on or below the malleoli on the target foot.
8. 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.
9. Has any other factor which may, in the opinion of the Investigator, compromise participation and/or follow-up in the study.
10. Body mass index (BMI) \>40 with plantar ulcer.
11. Heavy smoker (\>1 pack per day).

Primary outcomes:
measure: Primary endpoint:Q-RT-PCR, for the inflammation stage and the remodeling stage
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Secondary endpoint (1): IL-1b, IL-6, TNF, TGF, CXCL9, FGF2, and IL1RN!..ect.
timeFrame: Based on each visit window for the first review, and through study completion, an average of 1 year for the final review
measure: Secondary endpoint (2): iNOS, CD86, CD80, CD163, CD206, KRT14, MMP12..ect.
timeFrame: Based on each visit window for the first review, and through study completion, an average of 1 year for the final review
measure: Secondary endpoint (3): CO15A1, CD71, CD34..ect
timeFrame: Based on each visit window for the first review, and through study completion, an average of 1 year for the final review
measure: Secondary endpoint (4):target ulcer size evaluation report (Area: perimeter, length, width )
timeFrame: Based on each visit window for the first review, and through study completion, an average of 1 year for the final review
measure: Secondary endpoint (5): wound reduction rate of each target gene in each group
timeFrame: Based on each visit window for the first review, and through study completion, an average of 1 year for the final review
Other outcomes:
measure: Safety endpoint(1): Change from baseline in vital signs
timeFrame: Based on each visit window for the first review, and through study completion, an average of 1 year for the final review
measure: Safety endpoint(2): Change from baseline in physical examination
timeFrame: Based on each visit window for the first review, and through study completion, an average of 1 year for the final review
measure: Safety endpoint(3):Change from baseline in laboratory tests
timeFrame: Based on each visit window for the first review, and through study completion, an average of 1 year for the final review
Locations:
city: Taipei
country: Taiwan
facility: Kueiho Chen
Study officials:
References: