Foot Ulcer, DiabeticPhase 3NCT02554851
Efficacy and Safety Evaluation of the Intralesional Recombinant Human Epidermal Growth Factor (rhEGF) in Subjects With Diabetic Foot Ulcer.
A Phase 3 study testing recombinant human Epidermal Growth Factor (rhEGF) in people with Foot Ulcer, Diabetic and Epidermal Growth Factor, run by The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz).
Trial summary
Phase III clinical trial, multicenter, controlled, randomized, double-blind, with two parallel groups (experimental and control). Both study groups will receive standard therapy currently available in treatment centers for diabetic foot ulcer (DFU). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Foot Ulcer, Diabetic, Epidermal Growth Factor
- What is being tested?
- recombinant human Epidermal Growth Factor (rhEGF)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 304 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Dec 2023
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- DM type 1 or 2 diagnosis
- DFU persisting for a minimum of 4 weeks If the participant have more than one DFU, then it will be treated the one with the largest extension and that follows the inclusion and exclusion criteria.
- DFU 's rating according to the PEDIS system:Perfusion: grades 1 or 2; Extension: Area ≥ 2 cm2; Depth: grades 2 or 3; Infection: grades 1 or 2; Sensitivity: grade 2
- If the consented participant is classified as having infection grade 3 without the presence of osteomyelitis, it will be possible to treat it with antibiotics empirically. However, randomization will be made only after this treatment and only if the infection has regressed to grade 1 or 2;
Who cannot join
- Age less than 18 years;
- Pregnancy or breastfeeding (women in childbearing age will need to use a contraception method);
- Evidence of bone involvement : direct visualization of bone structures; positive survey (probe to bone) ; image investigation (simple x-ray or MRI);
- Urgent or imminent need of amputation;
- Eminent indication for revascularization;
- Glycated hemoglobin (HbA1c) counted greater than 11 %
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- Use of drugs that can affect or contribute to the healing of ulcers as corticosteroids; immunosuppressive; chemotherapy; other growth factors;
- Clinical signs of malnutrition or serum albumin <30 g / L;
- Angina pectoris classified as 3 or 4 (according to the Canadian Cardiovascular Society Angina Classification);
- Congestive heart failure class IV (according to the New York Heart Association);
- Severe hepatic impairment, defined as ALT and / or AST greater than 5 (five) times the normal maximum reference value;
- Acute renal failure, defined as serum creatinine levels equal or higher than 1.5 times the baseline value in the last 7 days (according to KDIGO and RIFLE classification);
- End-stage renal disease (creatinine clearance equal or lower than 30 ml / min or on dialysis);
- History or suspected neoplasia (according to previous laboratory tests, imaging or biopsy);
- Psychiatric disorders that may alter the participants evaluation, or prevent proper consent and / or cognitive aspects that demonstrate the possibility of noncompliance with treatment or the adoption of aseptic criteria;
- Occurrence of the following events 30 days prior to inclusion in the protocol: participation in other clinical studies; hypoglycemic coma (blood glucose less than or equal to 30 mg / dL with loss of consciousness or need for help); diabetic ketoacidosis or hyperosmolar state within 30 days prior to inclusion;
- Occurrence of the following events 60 days prior to inclusion in the protocol: hospitalization for acute coronary syndrome, percutaneous intervention (eg cardiac, cerebrovascular, aortic) or greater cardiac surgery; myocardial infarction; cerebrovascular accident; cardiac arrest; sustained ventricular tachycardia; acute coronary syndrome, in investigator opinion; uncontrolled severe hypertension, defined as systolic blood pressure equal or higher than 180 mmHg and / or diastolic blood pressure equal or higher than 110 mmHg;
About this study
Official title: Efficacy and Safety Evaluation of the Intralesional Recombinant Human Epidermal Growth Factor (rhEGF) in Subjects With Diabetic Foot Ulcer. Multicenter, Randomized, Double-blind, Placebo-controlled Study.
Phase III clinical trial, multicenter, controlled, randomized, double-blind, with two parallel groups (experimental and control). Both study groups will receive standard therapy currently available in treatment centers for diabetic foot ulcer (DFU). Associate with the standard therapy, it will be given the recombinant human Epidermal Growth Factor (rhEGF) to experimental group and in the control group, it will be given a formulation without pharmacological effect (placebo) in order to masking and control of intralesional application. Participants with type 1 and type 2 diabetes mellitus (DM) diagnosed with DFU for at least 4 weeks, treated in referral centers participating in the study, agreeing to participate after reading, understanding and signing of Informed Consent (IC); meet all the inclusion criteria; and presenting no exclusion criteria. The Informed Consent (IC) should be applied to potential participants, as recommended by the regulations and ethical consensus before beginning any procedure related to the clinical trial. In the early weeks, participants will be evaluated at the research centers by the study team (doctors and / or staff). The number of visits will be determined by the investigator, thus ensuring appropriate assistance to participants, and avoiding any complications with DFU. By meeting the eligibility requirements (inclusion and exclusion criteria), the participant will undergo a thorough evaluation of the DFU before the start of treatment. This assessment is precisely to classify the condition of the ulcer before treatment and provide relevant information for statistical analysis of the protocol. If eligible, the participant will be randomly set to treatment arm (placebo or rhEGF) and the administration of investigational product associated with predefined standardized outpatient therapy will be initiated. This administration occurs three times per week until the DFU is scarred, not exceeding 8 weeks of treatment (T.01 to T.08) .The study will be randomized and balanced according to the type and size of the DFU. This balancing is necessary to ensure that both treatment groups are homogeneous for participants under different conditions. All participants will be applied established standard therapy for the treatment of DFU. The objective is to provide regular care for healing and reduce possible bias in the efficacy analysis and product safety. After the treatment period (last dose of the experimental drug) the participant will start the follow-up period, with 16 weeks duration. The participant shall be subjected to weekly visits for ongoing assessment of DFU, however, according to the investigator, may result in unscheduled visits to assess local or general clinical events. After the monitoring period, the participant will be observed for 24 additional weeks, visits every 4 weeks (E.01 E.24 a) having beginning one week after the last visit of follow-up. This period is intended to assess possible events related to the efficacy and safety that can happen in the period, mainly for analysis of secondary endpoints.
- Conditions
- Foot Ulcer, Diabetic, Epidermal Growth Factor
- Being tested
- recombinant human Epidermal Growth Factor (rhEGF), Placebo
- Medical subject headings
- Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human Epidermal Growth Factor (rhEGF)Drug
Also called Heberprot-P®
The Heberprot-P® is a parenteral formulation, which is in a lyophilized powder vial presentation containing 75μg of recombinant Epidermal Growth Factor (rhEGF) for local application (intralesional) with the therapeutic potential to promote granulation and wound healing of DFU. The rhEGF is a polypeptide of 53 amino acids and has the ability to stimulate fibroblasts, keratinocytes and vascular endothelial cells proliferation. Then it contributes to its properties in scar tissue formation. The action mechanism is based on the interaction with specific receptors located on specifics cell membranes. The rhEGF was developed through recombinant DNA technology and it has been produced by biotechnological methods in Saccharomyces cerevisiae yeast line.
PlaceboOther
This group will receive the standard medication and the placebo drug. The placebo drug has the same formulation, except for the fact that it does not contain the recombinant human Epidermal Growth Factor (rhEGF).
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | This group will receive the standard medication and the placebo drug Receives: Other: Placebo |
| recombinant human Epidermal Growth Fact | Experimental | This group will receive the standard medication and the recombinant human Epidermal Growth Factor (HEBERPROT) Receives: Drug: recombinant human Epidermal Growth Factor (rhEGF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of participants with 100% healing at the end of follow-up
Contingency tables for the proportion of participants with 100% healing at this time period (16th week of treatment evaluation) with their respective frequencies and percentages, according to the treatment group will be generated; 95% confidence intervals for the proportion of participants with 100% healing at the end of follow-up will be generated for each group; range of 95% confidence interval for the difference between the proportions of participants with 100% healing in each treatment group at the end of follow-up will be generated; the confirmatory data analysis will be held for proportions, one-sided, in order to verify the superiority hypothesis envisaged, the sample design.
Measured: up to 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2015 (estimated)
- Study startJan 2017
- Primary completionDec 2019
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Foot Ulcer, DiabeticStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02554851
- Sponsor's protocol ID
- ASCLIN002/2015
- Status last verified
- Jun 2023
- First submitted
- 11 Sep 2015
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety Evaluation of the Intralesional Recombinant Human Epidermal Growth Factor (rhEGF) in Subjects With Diabetic Foot Ulcer. Multicenter, Randomized, Double-blind, Placebo-controlled Study.
- ClinicalTrials.gov ID
- NCT02554851
- Acronym / sponsor ID
- ASCLIN002/2015
- Conditions
- Foot Ulcer, Diabetic, Epidermal Growth Factor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 304 participants (actual)
- Lead sponsor
- The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)University, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2023 (estimated)
- First posted
- 18 Sep 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.
Phase III clinical trial, multicenter, controlled, randomized, double-blind, with two parallel groups (experimental and control). Both study groups will receive standard therapy currently available in treatment centers for diabetic foot ulcer (DFU). Associate with the standard therapy, it will be given the recombinant human Epidermal Growth Factor (rhEGF) to experimental group and in the control group, it will be given a formulation without pharmacological effect (placebo) in order to masking and control of intralesional application. Participants with type 1 and type 2 diabetes mellitus (DM) diagnosed with DFU for at least 4 weeks, treated in referral centers participating in the study, agreeing to participate after reading, understanding and signing of Informed Consent (IC); meet all the inclusion criteria; and presenting no exclusion criteria. The Informed Consent (IC) should be applied to potential participants, as recommended by the regulations and ethical consensus before beginning any procedure related to the clinical trial. In the early weeks, participants will be evaluated at the research centers by the study team (doctors and / or staff). The number of visits will be determined by the investigator, thus ensuring appropriate assistance to participants, and avoiding any complications with DFU. By meeting the eligibility requirements (inclusion and exclusion criteria), the participant will undergo a thorough evaluation of the DFU before the start of treatment. This assessment is precisely to classify the condition of the ulcer before treatment and provide relevant information for statistical analysis of the protocol. If eligible, the participant will be randomly set to treatment arm (placebo or rhEGF) and the administration of investigational product associated with predefined standardized outpatient therapy will be initiated. This administration occurs three times per week until the DFU is scarred, not exceeding 8 weeks of treatment (T.01 to T.08) .The study will be randomized and balanced according to the type and size of the DFU. This balancing is necessary to ensure that both treatment groups are homogeneous for participants under different conditions. All participants will be applied established standard therapy for the treatment of DFU. The objective is to provide regular care for healing and reduce possible bias in the efficacy analysis and product safety. After the treatment period (last dose of the experimental drug) the participant will start the follow-up period, with 16 weeks duration. The participant shall be subjected to weekly visits for ongoing assessment of DFU, however, according to the investigator, may result in unscheduled visits to assess local or general clinical events. After the monitoring period, the participant will be observed for 24 additional weeks, visits every 4 weeks (E.01 E.24 a) having beginning one week after the last visit of follow-up. This period is intended to assess possible events related to the efficacy and safety that can happen in the period, mainly for analysis of secondary endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Other: PlaceboThis group will receive the standard medication and the placebo drug |
| recombinant human Epidermal Growth Fact | Experimental | Drug: recombinant human Epidermal Growth Factor (rhEGF)This group will receive the standard medication and the recombinant human Epidermal Growth Factor (HEBERPROT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- DM type 1 or 2 diagnosis
- DFU persisting for a minimum of 4 weeks If the participant have more than one DFU, then it will be treated the one with the largest extension and that follows the inclusion and exclusion criteria.
- DFU 's rating according to the PEDIS system:Perfusion: grades 1 or 2; Extension: Area ≥ 2 cm2; Depth: grades 2 or 3; Infection: grades 1 or 2; Sensitivity: grade 2
- If the consented participant is classified as having infection grade 3 without the presence of osteomyelitis, it will be possible to treat it with antibiotics empirically. However, randomization will be made only after this treatment and only if the infection has regressed to grade 1 or 2;
Key exclusion criteria (17 listed)
- Age less than 18 years;
- Pregnancy or breastfeeding (women in childbearing age will need to use a contraception method);
- Evidence of bone involvement : direct visualization of bone structures; positive survey (probe to bone) ; image investigation (simple x-ray or MRI);
- Urgent or imminent need of amputation;
- Eminent indication for revascularization;
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 |
|---|---|---|
| recombinant human Epidermal Growth Factor (rhEGF)Also: Heberprot-P®The Heberprot-P® is a parenteral formulation, which is in a lyophilized powder vial presentation containing 75μg of recombinant Epidermal Growth Factor (rhEGF) for local application (intralesional) with the therapeutic potential to promote granulation and wound healing of DFU. The rhEGF is a polypeptide of 53 amino acids and has the ability to stimulate fibroblasts, keratinocytes and vascular endothelial cells proliferation. Then it contributes to its properties in scar tissue formation. The action mechanism is based on the interaction with specific receptors located on specifics cell membranes. The rhEGF was developed through recombinant DNA technology and it has been produced by biotechnological methods in Saccharomyces cerevisiae yeast line. | Drug | recombinant human Epidermal Growth Fact |
| PlaceboThis group will receive the standard medication and the placebo drug. The placebo drug has the same formulation, except for the fact that it does not contain the recombinant human Epidermal Growth Factor (rhEGF). | Other | placebo |
Primary outcome
The proportion of participants with 100% healing at the end of follow-up
Time frame: up to 9 months
Contingency tables for the proportion of participants with 100% healing at this time period (16th week of treatment evaluation) with their respective frequencies and percentages, according to the treatment group will be generated; 95% confidence intervals for the proportion of participants with 100% healing at the end of follow-up will be generated for each group; range of 95% confidence interval for the difference between the proportions of participants with 100% healing in each treatment group at the end of follow-up will be generated; the confirmatory data analysis will be held for proportions, one-sided, in order to verify the superiority hypothesis envisaged, the sample design.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing recombinant human Epidermal Growth Factor (rhEGF) in people with Foot Ulcer, Diabetic and Epidermal Growth Factor, run by The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz).
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 4 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
The proportion of participants with 100% healing at the end of follow-up (time frame: up to 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jun 2023.