Diabetic Foot UlcerPhase 1/2Remede d'OrNCT02361931
Topical Erythropoietin Hydrogel Formulation for Diabetic Foot Ulcers
A Phase 1/2 study testing A hydrogel containing erythropoietin and Hydrogel (as a part of SOC) in people with Diabetic Foot Ulcer, run by Remedor Biomed Ltd at 5 sites in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetic Foot Ulcer
- What is being tested?
- A hydrogel containing erythropoietin and Hydrogel (as a part of SOC)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 5 sitesIsrael
- Study dates
- 21 Mar 2016to 12 Jun 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must satisfy all of the following inclusion criteria to be included in the study:
- 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;
- 2 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;
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- 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.
Who cannot join
- Patients will be excluded from the study if they meet any of the following exclusion criteria:
- 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);
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- 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).
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Israel5 sites
HaEmek Medical Center
Afula
Rambam Health Care Campus
Haifa
Edith Wolfson Medical Center
Holon
Galilee Medical Center
Nahariya
Poriya Medical Center (a.k.a. Baruch Padeh Medical Center)
Tiberias
About this study
Official title: Prospective, Multicenter, Single-blind, Randomized, Controlled Clinical Trial on Safety and Efficacy of a Novel Topical Formulation Containing Erythropoietin for the Treatment of Diabetic Foot Ulcers
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.
Read the detailed description
Delayed healing of a neuroischaemic diabetic foot ulcer (DFU) has been related to prolonged local inflammatory response, an unstable provisional matrix, increased degradation of the extracellular matrix, lack of growth factors and their receptors that are crucial for healing, fibroblast dysfunction, impaired neovascularization, increased oxidative stress, and cellular apoptosis in the wound bed, all of which collectively hinder re-epithelialisation and wound closure.
Erythropoietin (EPO) is an approved drug which is widely used for treating anaemia. EPO is a well-known glycoprotein hormone, which is primarily produced by the tubular cells of the kidney. EPO is widely known for regulating the red blood cell mass by stimulating differentiation and proliferation of precursor cells and hindering apoptosis of erythroid cells in the bone marrow. Millions of people have received EPO since its market approval by the US Food and Drug Administration in 1989 as a treatment of anaemia in patients with chronic kidney disease and later on as a treatment for chemotherapy-associated anaemia. There is growing evidence that both systemic administration and topical EPO application to skin wounds in animals with experimentally-induced diabetes mellitus (DM) and in patients with DM accelerates the healing of these wounds. This accelerated wound healing is mediated by EPO because it concomitantly suppresses the inflammatory response and apoptosis and stimulates angiogenesis, re-epithelialization, and collagen deposition.
Growing studies in experimental healthy and diabetic animals have demonstrated that systemic or topical treatment with EPO onto acute and chronic wounds and burns is safe and effective. Recently, the molecular mechanisms of EPO action in wound repair have been elucidated. EPO acts on all cutaneous cells that are involved in the wound healing process by promoting cellular differentiation and proliferation, exerting cytoprotective actions, and inhibiting inflammation and apoptosis due to the presence of EPO receptors in these cells [Hamed et al. 2014].
The aim of this multicenter, single-blind, randomized, controlled clinical trial is to evaluate the safety and efficacy of topical RMD-G1 treatment for DFUs. This study is an exploratory proof-of-concept study on RMD-G1 treatment for DFU.
- Conditions
- Diabetic Foot Ulcer
- Being tested
- A hydrogel containing erythropoietin, Hydrogel (as a part of SOC)
- Keywords
- erythropoietin, diabetic chronic wounds, wound healing, chronic wounds, topical treatment, re-epithelization, inflammation
- Medical subject headings
- Diabetic Foot, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A hydrogel containing erythropoietinDrug
Also called Standard of care (SOC)
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.
Hydrogel (as a part of SOC)Drug
Also called Standard of care (SOC)
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Hydrogel (as a part of SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants without adverse events following RMD-G1 treatment
Absence of serious adverse events associated with the RMD-G1 treatment.
Measured: 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.
Measured: 12 weeks
Secondary outcomes (6)
Number of patients with hypersensitivity at the wound site.
Weekly assessments of wound site for signs of hypersensitivity to the RMD-G1 treatment.
Measured: 12 weeks
Speed of healing
The time to reach complete wound closure (days).
Measured: 12 weeks
Reduction of wound area
Absolute wound area regression (AWAR) (cm2) will be assessed weekly.
Measured: 12 weeks
Partial wound closure
The number of participants with a wound surface area regression ≥ 50% and ≥ 75% by week 4.
Measured: 4 weeks
Rate of wound closure
Mean rate of wound closure (sq. cm./day) will be assessed weekly.
Measured: 12 weeks
Recurrence of closed wounds
Number of wound recurrence cases
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2015 (estimated)
- Study start21 Mar 2016
- Primary completion11 Jun 2018
- Study completion12 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic Foot UlcerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Remedor Biomed Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yehuda Ullman, Professor, Study chair, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02361931
- Sponsor's protocol ID
- 0252-12-RMB
- Acronym
- Remede d'Or
- Status last verified
- Mar 2019
- First submitted
- 12 Aug 2012
- Last updated
- 19 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 33504262
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Multicenter, Single-blind, Randomized, Controlled Clinical Trial on Safety and Efficacy of a Novel Topical Formulation Containing Erythropoietin for the Treatment of Diabetic Foot Ulcers
- ClinicalTrials.gov ID
- NCT02361931
- Acronym / sponsor ID
- Remede d'Or / 0252-12-RMB
- Conditions
- Diabetic Foot Ulcer
- Keywords
- erythropoietin, diabetic chronic wounds, wound healing, chronic wounds, topical treatment, re-epithelization, inflammation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Remedor Biomed LtdIndustry (pharma, biotech, devices)
- Study start
- 21 Mar 2016 (actual)
- Primary completion
- 11 Jun 2018 (actual)
- Study completion
- 12 Jun 2018 (actual)
- First posted
- 12 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Delayed healing of a neuroischaemic diabetic foot ulcer (DFU) has been related to prolonged local inflammatory response, an unstable provisional matrix, increased degradation of the extracellular matrix, lack of growth factors and their receptors that are crucial for healing, fibroblast dysfunction, impaired neovascularization, increased oxidative stress, and cellular apoptosis in the wound bed, all of which collectively hinder re-epithelialisation and wound closure.
Erythropoietin (EPO) is an approved drug which is widely used for treating anaemia. EPO is a well-known glycoprotein hormone, which is primarily produced by the tubular cells of the kidney. EPO is widely known for regulating the red blood cell mass by stimulating differentiation and proliferation of precursor cells and hindering apoptosis of erythroid cells in the bone marrow. Millions of people have received EPO since its market approval by the US Food and Drug Administration in 1989 as a treatment of anaemia in patients with chronic kidney disease and later on as a treatment for chemotherapy-associated anaemia. There is growing evidence that both systemic administration and topical EPO application to skin wounds in animals with experimentally-induced diabetes mellitus (DM) and in patients with DM accelerates the healing of these wounds. This accelerated wound healing is mediated by EPO because it concomitantly suppresses the inflammatory response and apoptosis and stimulates angiogenesis, re-epithelialization, and collagen deposition.
Growing studies in experimental healthy and diabetic animals have demonstrated that systemic or topical treatment with EPO onto acute and chronic wounds and burns is safe and effective. Recently, the molecular mechanisms of EPO action in wound repair have been elucidated. EPO acts on all cutaneous cells that are involved in the wound healing process by promoting cellular differentiation and proliferation, exerting cytoprotective actions, and inhibiting inflammation and apoptosis due to the presence of EPO receptors in these cells [Hamed et al. 2014].
The aim of this multicenter, single-blind, randomized, controlled clinical trial is to evaluate the safety and efficacy of topical RMD-G1 treatment for DFUs. This study is an exploratory proof-of-concept study on RMD-G1 treatment for DFU.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group (erythropoietin) | Experimental | Drug: A hydrogel containing erythropoietin10 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. |
| Control group (standard of care) | Placebo comparator | Drug: Hydrogel (as a part of SOC)10 patients receive SOC alone daily for 12 weeks. A moisturizing gel is applied on wound bed as a part of SOC. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must satisfy all of the following inclusion criteria to be included in the study:
- 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;
- 2 sq.cm. ≤ Wound area at start of treatment ≤ 10 sq.cm.;
Key exclusion criteria (15 listed)
- Patients will be excluded from the study if they meet any of the following exclusion criteria:
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| A hydrogel containing erythropoietinAlso: Standard of care (SOC)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. | Drug | Treatment group (erythropoietin) |
| Hydrogel (as a part of SOC)Also: Standard of care (SOC)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. | Drug | Control group (standard of care) |
Primary outcome
Number of participants without adverse events following RMD-G1 treatment
Time frame: 24 weeks
Absence of serious adverse events associated with the RMD-G1 treatment.
Number of participants with the reduction of wound area by 75%$ or more
Time frame: 12 weeks
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.
6 secondary outcomes
Number of patients with hypersensitivity at the wound site.
Time frame: 12 weeks
Speed of healing
Time frame: 12 weeks
Reduction of wound area
Time frame: 12 weeks
Partial wound closure
Time frame: 4 weeks
Rate of wound closure
Time frame: 12 weeks
Recurrence of closed wounds
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2019.
- Derived from this study: PubMed 33504262Hamed 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yehuda Ullman, Professor study chair
Rambam Health Care Campus
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing A hydrogel containing erythropoietin and Hydrogel (as a part of SOC) in people with Diabetic Foot Ulcer, run by Remedor Biomed Ltd at 5 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants without adverse events following RMD-G1 treatment (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02361931, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2019.