Topical Erythropoietin Hydrogel Formulation for Diabetic Foot Ulcers

NCT02361931 | Completed Phase 1

• 1 other identifier: 0252-12-RMB
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

Remedor has developed a patented technology (RMD-G1), which comprises erythropoietin (EPO) as the active pharmaceutical ingredient (API) in a carbopol-based hydrogel with an FN matrix. RMD-G1 was designed to maintain EPO stability and activity over long periods and to optimize the administration of EPO onto the wound bed. RMD-G1 is indicated for treating DFUs in adult patients with diabetes mellitus and aims to accelerate the healing of diabetic foot ulcers. RMD-G1 is an adjunct treatment, and not a substitute for good diabetic wound care, which includes initial debridement, wound cleansing, pressure relief, and infection control. In this trial, RMD-G1 is applied daily onto a clean wound at 0.25g per sq. cm. wound surface. After its application, the wound will be covered with a dressing in order to prevent leakage of the hydrogel and contamination of the wound area.

Conditions

Diabetic Foot Ulcer

Keywords

erythropoietin; diabetic chronic wounds; wound healing; chronic wounds; topical treatment; re-epithelization; inflammation

Outcome Measures

Primary Outcomes (2)

• Number of participants without adverse events following RMD-G1 treatment

  Absence of serious adverse events associated with the RMD-G1 treatment.

  24 weeks

• Number of participants with the reduction of wound area by 75%$ or more

  Wound area will be assessed weekly for 75% closure or more of the wound area, which is defined as 75% epithelialization of the wound with no secretions.

  12 weeks

Secondary Outcomes (6)

• Number of patients with hypersensitivity at the wound site.

  12 weeks

• Speed of healing

  12 weeks

• Reduction of wound area

  12 weeks

• Partial wound closure

  4 weeks

• Rate of wound closure

  12 weeks

Study Arms (2)

Treatment group (erythropoietin)

EXPERIMENTAL

10 patients receive RMD-G1 (gel with 2000 IU/ml of erythropoietin) as an adjunct therapy to standard of care (SOC). Topical application on wound bed, daily for 12 weeks.

Drug: A hydrogel containing erythropoietin

Control group (standard of care)

PLACEBO COMPARATOR

10 patients receive SOC alone daily for 12 weeks. A moisturizing gel is applied on wound bed as a part of SOC.

Drug: Hydrogel (as a part of SOC)

Interventions

A hydrogel containing erythropoietin DRUG

Standard of wound care, which includes initial debridement, wound cleansing, pressure relief, and infection control. RMD-G1 applied daily onto a clean wound at 0.25g per sq.cm. of wound surface. After its application, the wound is covered with a dressing in order to prevent leakage of the gel and contamination of the wound area.

Also known as: Standard of care (SOC)

Treatment group (erythropoietin)

Hydrogel (as a part of SOC) DRUG

Standard of wound care, which includes initial debridement, wound cleansing, pressure relief, and infection control. Hydrogel applied daily onto a clean wound at 0.25g per sq.cm. of wound surface. After its application, the wound is covered with a dressing in order to prevent leakage of the gel and contamination of the wound area.

Also known as: Standard of care (SOC)

Control group (standard of care)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female over the age of 18;
• Diabetes Mellitus type 2;
• Have a single non-infected Diabetic Hard-to-Heal wound (ulcers/foot ulcers), Wagner grade I or II documented for at least 4 weeks that has not shown signs of healing despite standard treatment;
• sq.cm. ≤ Wound area at start of treatment ≤ 10 sq.cm.;
• At least moderate blood perfusion into the affected limb as defined by Ankle Brachial Index (ABI) of \>0.4 or if ABI \>1.3 then toe pressure \> 50 mmHg;
• Undergo a current physical examination, which reveals no clinically significant abnormalities, except diabetes or diabetic ulcer/wound related condition;
• Be available for the entire study period, and be able and willing to adhere to protocol requirements;
• Provide written informed consent prior to admission into the study;
• no surgical revascularization of the limb with the DFU was done in the previous two months.

You may not qualify if:

• Diabetes Mellitus non Type 2;
• Have a glycosylated haemoglobin (HbA1c) \>10.0%;
• Have a body mass index (BMI) \> 40 Kg/m2;
• Have visible bone exposure at wound site;
• Subjects whose study ulcer size decreases by more than 30% during this initial standard-of-care phase (pre-treatment phase);
• Have any signs of infection in the wound (which could be linked to raised body temperature), abscess, cellulitis, necrosis, erythema, mild drainage or known osteomyelitis;
• Have a history of HIV or a clinically significant cardiac, gastrointestinal, endocrine, neurological, liver, or kidney disease;
• Anemia (Hemoglobin \< 9 g/dL) or White Blood Cells count \> 11,000/μL or Platelets count \< 100,000/μL or liver function tests \> 3 times upper normal lab values or Creatinine \> 3 mg/dL; any indication of malnourishment (Albumin \< 3 g/dL); INR\>2 or any other clinically significant blood and urinalysis tests per the physician's discretion
• Have any clinically significant chronic or acute illness during the 4 weeks prior to admission into the study, except diabetes type2 or during screening period;
• Patients on concomitant medications that alter blood glucose levels (e.g. ACE inhibitors, lipid lowering agents, etc.) who have not been on a stable dosage regimen for at least 4 weeks prior to entry into the study and who cannot maintain a stable dosage throughout the study;
• Malignant disease except Basal Cell Carcinoma or Cervical Carcinoma in situ; Chemotherapy treatment or severely immunosuppressed for any reason that would limit or preclude healing in the opinion of the Investigator;
• Females who are pregnant, lactating, of child-bearing potential, or post-menopausal for less than 2 years, not using a medically approved method of contraception (i.e., oral, transdermal, or implanted contraceptives, intrauterine device, diaphragm, condom, abstinence, or surgical sterility), or females who test positive on a blood-based pregnancy test;
• Participation in a clinical study or use of an investigational drug within 30 days prior to admission to this study;
• Residing in a nursing facility and/or are bed-ridden (unable to come to receive treatment at the clinic).

Sponsors & Collaborators

• Remedor Biomed Ltd: lead

Study Sites (5)

HaEmek Medical Center

Afula, Israel

Location

Rambam Health Care Campus

Haifa, Israel

Location

Edith Wolfson Medical Center

Holon, Israel

Location

Galilee Medical Center

Nahariya, Israel

Location

Poriya Medical Center (a.k.a. Baruch Padeh Medical Center)

Tiberias, Israel

Location

Related Publications (1)

• Hamed S, Ullmann Y, Belokopytov M, Shoufani A, Kabha H, Masri S, Feldbrin Z, Kogan L, Kruchevsky D, Najjar R, Liu PY, Kerihuel JC, Akita S, Teot L. Topical Erythropoietin Accelerates Wound Closure in Patients with Diabetic Foot Ulcers: A Prospective, Multicenter, Single-Blind, Randomized, Controlled Trial. Rejuvenation Res. 2021 Aug;24(4):251-261. doi: 10.1089/rej.2020.2397. Epub 2021 Apr 1.

  PMID: 33504262 DERIVED

MeSH Terms

Conditions

Diabetic Foot; Inflammation

Interventions

Standard of Care; Hydrogels

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Gels; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Yehuda Ullman, Professor

  Rambam Health Care Campus

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2012
• First Posted: February 12, 2015
• Study Start: March 21, 2016
• Primary Completion: June 11, 2018
• Study Completion: June 12, 2018
• Last Updated: March 19, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

IL (5)