Evaluate the Efficacy and Safety of ON101 Cream for the Treatment of Chronic Diabetic Foot Ulcers

• Sponsor: Oneness Biotech Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01898923
• Collaborator: (none)
• Enrollment: 236
• Locations: 21
• Arms: 2
• Actual Duration (Months): 89.6
• Patients Per Site: 11.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of the new treatment of WH-1 ointment compared to Aquacel® Hydrofiber® dressing, applied to chronic diabetic foot ulcers for up to 16 weeks.An additional objective of this study is to collect safety information including adverse events and clinical laboratory abnormalities.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Foot	Drug: ON101 Cream; Other: Aquacel® Hydrofiber® dressing	Phase 3

Detailed Description

This trial is designed as a randomized, evaluator blinded, active-controlled, multi-center study comparing the efficacy and safety of WH-1 ointment and Aquacel® Hydrofiber® dressing in the treatment of diabetic foot ulcers. Independent evaluators who blinded to subjects' treatment will evaluate whether the wound has healed. Eligible subjects will be randomized to receive either WH-1 ointment or Aquacel® Hydrofiber® dressing in a 1:1 allocation. The study treatment will be applied to the selected ulcer for a maximum period of 16 weeks, until the wound/ulcer closure (wound size of 0) for two consecutive visits at least 2 weeks apart, or until the subject exited the study as treatment failure. After that, all subjects regardless of wound healing at the end of comparison period will be followed for 12 weeks to investigate durability. During the follow-up period, Aquacel® Hydrofiber® dressing will be applied for subjects who have unhealed or with recurrent wound. Each target ulcer with wound photographs for blind assessment will be monitored at each scheduled visit.

One interim analysis is planned at around 50% of study information; the final analysis will be conducted at the end of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 236 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Study to Evaluate the Efficacy and Safety of ON101 Cream for the Treatment of Chronic Diabetic Foot Ulcers
• Actual Study Start Date: Nov 23, 2012
• Actual Primary Completion Date: May 11, 2020
• Actual Study Completion Date: May 11, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ON101 Cream ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks.	Drug: ON101 Cream; Other Names: WH-1
Other: Aquacel® Hydrofiber® dressing Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days.	Other: Aquacel® Hydrofiber® dressing

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Ulcer Closure [16 weeks]

   The primary variable is the number of target ulcers healed in each group within 16 weeks. The primary efficacy outcome is the comparison of the incidence of complete healing of the target ulcer between the two treatment groups at the end of treatment. For the purpose of this study a complete healing will be defined as complete epithelialization which is maintained with no drainage for at least 2 weeks and is confirmed by a blinded assessor.

Secondary Outcome Measures

1. The Time of Healing Rate [16 weeks]

   Time to complete ulcer healing, The time of the original healing will be taken as the time to healing.

2. Change in Ulcer Area [16 weeks]

   Percentage change in ulcer surface area from baseline

3. Percentage of Participants With a 50% Reduction of Ulcer Surface Area [16 weeks]

   Percentage of subjects with a 50% reduction of ulcer surface area

4. Incidence of Infection of the Target Ulcer [16 weeks]

   Incidence of infection of the target ulcer

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Has signed a written informed consent prior to the first study evaluation;

2. Male or female is at least 20 and < 80 years of age;

3. Diabetes mellitus (type 1 or 2) with an HbA1c < 12.0% measured during screening or within three months prior to randomization;

4. An ankle brachial index on the target limb at least 0.8 measured during screening or within three months prior to randomization;

5. The target ulcer must have the following characteristics:

• Grade 1 or 2 per Wagner Ulcer Classification System;

• No higher than the ankle;

• No active infected;

• A cross-sectional area of between 1 and 25 cm2 post-debridement;

• Present for at least 4 weeks before randomization;

1. If female and of childbearing potential has a negative pregnancy test and is not breastfeeding at screening visit;

2. Able and willing to attend the scheduled visits and comply with study procedures.

Exclusion Criteria:

1. Presence of necrosis, purulence or sinus tracts that cannot be removed by debridement;

2. Acute Charcot's neuroarthropathy as determined by clinical and/or radiographic examination;

3. Has undergone revascularization procedure aimed at increasing blood flow in the treatment target limb < 4 weeks prior to randomization;

4. Poor nutritional status defined as an albumin < 2.5 g/dL;

5. Aspartate Aminotransferase(AST, GOT) and/or Alanine Aminotransferase(ALT, GPT) >3 x the normal upper limit;

6. Serum Creatinine >2 x the normal upper limit;

7. Treatment with immunosuppressive or chemotherapeutic agents, radiotherapy or systemic corticosteroids less than 4 weeks before randomization;

8. Use of any investigational drug or therapy within the 4 weeks prior to randomization;

9. 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;

10. Judged by the investigator not to be suitable for the study for any other reason.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Limb Preservation Platform, Inc.	Fresno	California	United States
2	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China
3	Nanfang Hospital of Southern Medical University	Guanzhou	Guangdong	China
4	The First Affiliated Hospital, Sun Yat-sen University	Guanzhou	Guangdong	China
5	The First Affiliated Hospital of Henan Science & Technology University	Luoyang	Henan	China
6	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China
7	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu	China
8	Shandong Provincial Hospital	Jinan	Shandong	China
9	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China
10	Shanghai TCM-Interated Hospital	Shanghai	Shanghai	China
11	Chang Gung Medical Hospital_Kaohsiung	Kaohsiung		Taiwan
12	Buddhist Tzu Chi Medical Hospital	New Taipei City		Taiwan
13	MacKay Memorial Hospital-Tamsui Branch	New Taipei City		Taiwan
14	China Medical University Hospital	Taichung City		Taiwan
15	Chi Mei Medical Center-Yongkang	Tainan City		Taiwan
16	MacKay Memorial Hospital-Taipei Branch	Taipei City		Taiwan
17	National Taiwan University Hospital	Taipei City		Taiwan
18	Taipei Veterans General Hospital	Taipei City		Taiwan
19	Tri-Service General Hospital	Taipei City		Taiwan
20	Chang Gung Medical Hospital_Linkou	Taoyuan City		Taiwan
21	China Medical University Hospital-Beigang Branch	Yunlin		Taiwan	651

Sponsors and Collaborators

• Oneness Biotech Co., Ltd.

Investigators

• Study Director: Henry Chang, Oneness Biotech

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 25, 2019

More Information

Publications

None provided.

• Responsible Party: Oneness Biotech Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01898923
• Other Study ID Numbers: ON101CLCT02
• First Posted: Jul 15, 2013
• Last Update Posted: Apr 14, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Oneness Biotech Co., Ltd.: WH-1,Diabetic Foot,Ulcer
• Additional relevant MeSH terms: Diabetic Foot; Foot Ulcer; Carboxymethylcellulose Sodium

Study Results

Participant Flow

Arm/Group Title	ON101 Cream	Aquacel® Hydrofiber® Dressing
Arm/Group Description	ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks. ON101 Cream	Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days. Aquacel® Hydrofiber® dressing
Period Title: Overall Study
STARTED	122	114
COMPLETED	106	93
NOT COMPLETED	16	21

Baseline Characteristics

Arm/Group Title	ON101 Cream	Aquacel® Hydrofiber® Dressing	Total
Arm/Group Description	ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks. ON101 Cream	Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days. Aquacel® Hydrofiber® dressing	Total of all reporting groups
Overall Participants	122	114	236
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.4 (10.6)	56.6 (11.3)	57.0 (10.9)
Sex: Female, Male (Count of Participants)
Female	29 23.8%	32 28.1%	61 25.8%
Male	93 76.2%	82 71.9%	175 74.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	4 3.3%	4 3.5%	8 3.4%
China	20 16.4%	20 17.5%	40 16.9%
Taiwan	98 80.3%	90 78.9%	188 79.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Ulcer Closure
Description	The primary variable is the number of target ulcers healed in each group within 16 weeks. The primary efficacy outcome is the comparison of the incidence of complete healing of the target ulcer between the two treatment groups at the end of treatment. For the purpose of this study a complete healing will be defined as complete epithelialization which is maintained with no drainage for at least 2 weeks and is confirmed by a blinded assessor.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON101 Cream	Aquacel® Hydrofiber® Dressing
Arm/Group Description	ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks. ON101 Cream	Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days. Aquacel® Hydrofiber® dressing
Measure Participants	122	114
Count of Participants [Participants]	74 60.7%	40 35.1%

2. Secondary Outcome

Title	The Time of Healing Rate
Description	Time to complete ulcer healing, The time of the original healing will be taken as the time to healing.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON101 Cream	Aquacel® Hydrofiber® Dressing
Arm/Group Description	ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks. ON101 Cream	Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days. Aquacel® Hydrofiber® dressing
Measure Participants	122	114
Median (95% Confidence Interval) [weeks]	14	NA

3. Secondary Outcome

Title	Change in Ulcer Area
Description	Percentage change in ulcer surface area from baseline
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON101 Cream	Aquacel® Hydrofiber® Dressing
Arm/Group Description	ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks. ON101 Cream	Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days. Aquacel® Hydrofiber® dressing
Measure Participants	122	114
week 16	-78 (42.6)	-78 (34.9)
week 2	-36 (32.9)	-38 (29.3)

4. Secondary Outcome

Title	Percentage of Participants With a 50% Reduction of Ulcer Surface Area
Description	Percentage of subjects with a 50% reduction of ulcer surface area
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON101 Cream	Aquacel® Hydrofiber® Dressing
Arm/Group Description	ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks. ON101 Cream	Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days. Aquacel® Hydrofiber® dressing
Measure Participants	122	114
Count of Participants [Participants]	101 82.8%	98 86%

5. Secondary Outcome

Title	Incidence of Infection of the Target Ulcer
Description	Incidence of infection of the target ulcer
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON101 Cream	Aquacel® Hydrofiber® Dressing
Arm/Group Description	ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks. ON101 Cream	Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days. Aquacel® Hydrofiber® dressing
Measure Participants	122	114
Count of Participants [Participants]	6 4.9%	7 6.1%

Adverse Events

Time Frame	Adverse event collection began after study intervention was initiated and continued through the entire study visit. (Day 1 to Day 197)
Arm/Group Title	ON101 Cream		Aquacel® Hydrofiber® Dressing
Arm/Group Description	ON101 Cream (1.25%),15g ointment per tube. Twice daily for up to 16 weeks. ON101 Cream		Aquacel® Hydrofiber® dressings will be changed daily, on alternate days or three times a week according to need, but not longer than 7 days. Aquacel® Hydrofiber® dressing
All Cause Mortality
	ON101 Cream		Aquacel® Hydrofiber® Dressing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/122 (0.8%)		0/114 (0%)
Serious Adverse Events
	ON101 Cream		Aquacel® Hydrofiber® Dressing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/122 (11.5%)		9/114 (7.9%)
Cardiac disorders
Cardiac failure	1/122 (0.8%)	1	1/114 (0.9%)	1
Acute myocardial infarction	1/122 (0.8%)	1	0/114 (0%)	0
Infections and infestations
Abscess limb	2/122 (1.6%)	2	0/114 (0%)	0
Appendicitis	1/122 (0.8%)	1	0/114 (0%)	0
Cellulitis	3/122 (2.5%)	3	1/114 (0.9%)	1
Diabetic foot infection	0/122 (0%)	0	1/114 (0.9%)	1
Infected skin ulcer	0/122 (0%)	0	2/114 (1.8%)	2
Localised infection	1/122 (0.8%)	1	0/114 (0%)	0
Necrotising fasciitis	1/122 (0.8%)	1	0/114 (0%)	0
Osteomyelitis	1/122 (0.8%)	1	2/114 (1.8%)	2
Pneumonia	0/122 (0%)	0	1/114 (0.9%)	1
staphylococcal sepsis	0/122 (0%)	0	1/114 (0.9%)	1
Urinary tract infection	1/122 (0.8%)	1	1/114 (0.9%)	1
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/122 (0%)	0	1/114 (0.9%)	1
Hypoglycaemia	1/122 (0.8%)	1	0/114 (0%)	0
Hypokalaemia	1/122 (0.8%)	1	0/114 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/122 (0.8%)	1	0/114 (0%)	0
Soft tissue disorder	1/122 (0.8%)	1	0/114 (0%)	0
Nervous system disorders
Cerebral arteriosclerosis	1/122 (0.8%)	1	0/114 (0%)	0
Cerebrovascular accident	1/122 (0.8%)	1	0/114 (0%)	0
Ischaemic cerebral infarction	1/122 (0.8%)	1	0/114 (0%)	0
Loss of consciousness	1/122 (0.8%)	1	0/114 (0%)	0
Renal and urinary disorders
Hydronephrosis	1/122 (0.8%)	1	0/114 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/122 (0.8%)	1	0/114 (0%)	0
Pulmonary oedema	1/122 (0.8%)	1	0/114 (0%)	0
Skin and subcutaneous tissue disorders
Diabetic foot	1/122 (0.8%)	1	2/114 (1.8%)	2
Other (Not Including Serious) Adverse Events
	ON101 Cream		Aquacel® Hydrofiber® Dressing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/122 (5.7%)		5/114 (4.4%)
General disorders
Peripheral swelling	1/122 (0.8%)	1	0/114 (0%)	0
Pyrexia	0/122 (0%)	0	1/114 (0.9%)	1
Infections and infestations
Cellulitis	0/122 (0%)	0	1/114 (0.9%)	1
Osteomyelitis	0/122 (0%)	0	1/114 (0.9%)	1
Staphylococcal infection	1/122 (0.8%)	1	0/114 (0%)	0
Injury, poisoning and procedural complications
Wound complication	1/122 (0.8%)	1	0/114 (0%)	0
Investigations
Weight increased	1/122 (0.8%)	1	0/114 (0%)	0
Metabolism and nutrition disorders
Hyperuricaemia	2/122 (1.6%)	2	0/114 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	0/122 (0%)	0	1/114 (0.9%)	1
Skin and subcutaneous tissue disorders
Dermatitis contact	1/122 (0.8%)	1	0/114 (0%)	0
Diabetic foot infection	0/122 (0%)	0	1/114 (0.9%)	1
Eczema	2/122 (1.6%)	2	0/114 (0%)	0
Erythema	1/122 (0.8%)	1	0/114 (0%)	0
Rash	1/122 (0.8%)	1	0/114 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.