Clinical trial NCT05764226: Freshly Manufactured 35kDa Hyaluronan Fragment HA35 for the Treatment of Chronic Wounds
Official title: A Clinical Study of Freshly Manufactured 35kDa Hyaluronan Fragment HA35 for Treatment of Chronic Wounds
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Wounds
Keywords: Hyaluronidase
35kDa hyaluronan fragment
HA35
Tissue permeability
Chronic wound
Wound healing
Lead sponsor: Nakhia Impex LLC
Sponsor class: INDUSTRY
Collaborators: name: Mongolian National University of Medical Sciences
First posted: 2023-03-10
Enrollment: 20
Sex: ALL
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: An open label single arm before and after treatment comparison clinical study
Primary purpose: TREATMENT

Brief summary: In this research, the patients with chronic wounds accompanied by pain were treated by injecting freshly manufactured tissue permeable hyaluronan fragment HA35 into the tissue under the heath skin immediately surrounding the chronic wounds.

Detailed description: Chronic wounds are wounds or ulcers that do not heal properly and are generally classified as venous, arterial, diabetic, traumatic, and pressure chronic wound. Persistent chronic inflammation is a hallmark for chronic wound or trauma and is also often associated with inflammatory and neuropathic pain.

Injections of high molecular weight hyaluronan HA into joint cavity have been used for many years in treatment of joint pain as well as associated inflammation. Still, due to the high viscosity and poor tissue permeability of high molecular weight HA, it is unsuitable for treating chronic wound or trauma pain and the associated inflammation. In this study, the investigators found that hyaluronidase PH20 could cleave high molecular weight hyaluronan into 35kDa low molecular weight hyaluronan fragment HA35. The freshly-made hyaluronan fragment HA35 had great tissue permeability compared with high molecular HA. Our previous clinical studies (http://www.clinicaltrials.gov) have shown freshly-made hyaluronan fragment HA35 effectively treating shoulder, neck and back pain as well as the severe pain associated with shingles. In this study, the tissue-permeable 35kDa hyaluronan fragment HA35 was freshly manufactured by mixing hyaluronidase PH20 injectable solution and high-molecular-weight hyaluronan HA injectable solution. The therapeutic effect of the tissue-permeable hyaluronan fragment HA35 for treatment of pain associated chronic wounds was studied in a single-arm off-label used, before and after treatment comparison, clinical study similar to others.

Both recombinant human hyaluronidase PH20 (Hylenex, Halozyme Inc) and bovine testis-derived hyaluronidase PH20 (H31022111) are able to cleave high molecule weight hyaluronan into 35 kDa hyaluronan fragments HA35 (L20200708MP07707, Ministry of Health, Mongolia). This clinical study uses 35kDa low molecular weight hyaluronan fragment HA35 which was freshly manufactured by mixing bovine testis-derived hyaluronidase PH20 injection (H31022111) with high molecular weight hyaluronan HA injection (H20174089) for 20 minutesat at room temperature.

In this study, 20 hospitalized patients with chronic wounds accompanied by pain were treated with the freshly manufactured 35 kDa low molecular weight hyaluronan fragment HA35. There were 8 patients with diabetic chronic wounds, 4 patients with chronic venous wounds, 2 patients with chronic arterial wounds, 6 patients with traumatic and chronic pressure wounds. Among these patients, there are 12 males and 8 females, having average age of 55±10 years. The creteria for the chronic wound in this study were the wound that has not been healed more than 3 months. All the chronic wounds were associated with significantly pain. All the wounds were clinically presented by surface darkenes and purulent secretions on the wounds, and darkness, redness, swelling and dryness and broken surface of the skin surrounding the wounds. This study is an open-label clinical study in which no information is withheld from participantes and investigators. In this study, the therapeutic effect was studied by comparison of those of before and after treatment in a single-arm study. The pain associated with the wounds and degree of healing of the wounds including the size of fresh granulation area on the wound, the degree of darkness or redness, dryness and broken surface of the skin surrounding the wound, and the size of the wound were observed and recorded.

Eligibility criteria: Inclusion Criteria:

1. The chronic wounds of painful diabetic wounds, venous wounds, arterial wounds, traumatic and pressure wounds which had not been closed more than 3 months.
2. All the chronic wounds were clinically presented by surface darkeness and purulent secretions on the wounds, and darkness or redness, swelling, dryness and broken.
3. Surface of the skin immediately surrounding the wounds.
4. Subject agrees to be compliant with study related visit and treatment schedule.
5. Written informed consent.

Exclusion Criteria:

1. History of wound healing abnormalities or a medical condition that is known to be associated with abnormal wound healing.
2. Subjects with any known coagulation disorder.

Primary outcomes:
measure: The pain score
timeFrame: 24 hours
Secondary outcomes:
measure: The self-quantitative assessment scale
timeFrame: 10 days
Other outcomes:
Locations:
city: Harbin
country: China
facility: Far East Hospital
state: Heilongjiang
Study officials:
References:
citation: Jia X, Shi M, Wang Q, Hui J, Shofaro JH, Erkhembayar R, Hui M, Gao C, Gantumur MA. Anti-Inflammatory Effects of the 35kDa Hyaluronic Acid Fragment (B-HA/HA35). J Inflamm Res. 2023 Jan 13;16:209-224. doi: 10.2147/JIR.S393495. eCollection 2023.
citation: APPLICATION OF LOW-MOLECULAR-WEIGHT HYALURONIC ACID(LMW-HA) FRAGMENTS(INJECTION) WO/2017/186088 US20200254005 EP3479830 AU2017255833 CA3049286