Efficacy and Safety Evaluation of the Intralesional Recombinant Human Epidermal Growth Factor (rhEGF) in Subjects With Diabetic Foot Ulcer.

June 14, 2023 updated by: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
304

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. DM type 1 or 2 diagnosis
  2. 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.
  3. 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;

Exclusion Criteria:

  1. Age less than 18 years;
  2. Pregnancy or breastfeeding (women in childbearing age will need to use a contraception method);
  3. Evidence of bone involvement : direct visualization of bone structures; positive survey (probe to bone) ; image investigation (simple x-ray or MRI);
  4. Urgent or imminent need of amputation;
  5. Eminent indication for revascularization;
  6. Glycated hemoglobin (HbA1c) counted greater than 11 %
  7. Use of drugs that can affect or contribute to the healing of ulcers as corticosteroids; immunosuppressive; chemotherapy; other growth factors;
  8. Clinical signs of malnutrition or serum albumin <30 g / L;
  9. Angina pectoris classified as 3 or 4 (according to the Canadian Cardiovascular Society Angina Classification);
  10. Congestive heart failure class IV (according to the New York Heart Association);
  11. Severe hepatic impairment, defined as ALT and / or AST greater than 5 (five) times the normal maximum reference value;
  12. 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);
  13. End-stage renal disease (creatinine clearance equal or lower than 30 ml / min or on dialysis);
  14. History or suspected neoplasia (according to previous laboratory tests, imaging or biopsy);
  15. 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;
  16. 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;
  17. 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;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: placebo
This group will receive the standard medication and the placebo drug
Other: Placebo
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).
Experimental: recombinant human Epidermal Growth Fact
This group will receive the standard medication and the recombinant human Epidermal Growth Factor (HEBERPROT)
Drug: recombinant human Epidermal Growth Factor (rhEGF)
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.
Other Names:
  • Heberprot-P®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
up to 9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2019

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 11, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 18, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 15, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ASCLIN002/2015

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