Diabetic Foot Ulcer
Conditions
Brief summary
The purpose of the current Study is to determine the safety and effectiveness of Galnobax® plus Standard of Care versus only Standard of Care, in treating Diabetic Foot Ulcers (DFU). In addition, Study is designed to investigate the safety of Galnobax® vehicle for establishing non-deleterious effects of Vehicle on wound healing in the Subjects with DFU. The study is being conducted in 350 subjects being recruited in about 30 centers in India.
Detailed description
The current study is a Prospective, Multicenter, Randomized, Double-Blind, Phase 3 Study to Evaluate the Safety and Efficacy of a Gel Formulation of Esmolol Hydrochloride (Galnobax®) in Treating Diabetic Foot Ulcers. The study evaluates the safety and effectiveness of Galnobax® plus Standard of Care versus only Standard of Care, in treating Diabetic Foot Ulcers (DFU). In addition, Study is designed to investigate the safety of Galnobax® vehicle for establishing non-deleterious effects of Vehicle on wound healing in the Subjects with DFU.
Interventions
Galnobax-14% gel application along with Standard of Care
OTHEROnly Standard of Care
Only Standard of Care treatment
OTHERVehicle Gel
Vehicle gel application along with Standard of Care
Sponsors
Novalead Pharma Private Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The subject will be masked from the treatment by the Study Nurse (care giver) by using blinder during each treatment application. The site has two separate teams (blinded and unblinded) for masking. The unblinded investigator performs application of treatment during each treatment visit of subject to the site.
Intervention model description
Prospective, Multicenter, Randomized, Double-Blind, Parallel groups
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects, male or female, aged 18 to 75 years (inclusive) with Type 1 or Type 2 diabetes undergoing therapy for glycemic control 2. Subject has glycosylated hemoglobin, HbA1C, ≤ 12% 3. Subject with diagnosis of neuropathic foot ulcer by 10g monofilament test 4. Subject has adequate vascular perfusion of the affected limb, confirmed by Ankle-Brachial Index (ABI) ≥ 0.65 and ≤ 1.3 5. Presence of at least one DFU that meets all of the following criteria: 1. A full-thickness ulcer of Grade A1 as per Texas classification system; 2. Ulcer is located below or up to 5 cm above the malleoli (excluding ulcers between the toes); 3. Ulcer size (area) is ≥ 2 cm2 and ≤ 15 cm2 (post-debridement); 4. There is a minimum 3 cm margin between the qualifying Target Ulcer and any other ulcers on the specified foot, post-debridement; 5. No exposed bone, tendon, muscle, ligament or joint capsule, and no tunneling, undermining, or sinus tracts; 6. Unresponsive to ulcer care and open for at least 6 weeks at the time of the Screening Visit; 7. Ulcer is non-infected as determined by clinical assessment and complete hemogram; 8. Ulcer has a clean, granulating base free of adherent slough to the greatest extent possible as per Investigator; 9. Ulcer area reduction \< 30% from the Screening Visit to Baseline visit 6. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Investigator 7. Subject, if female of child-bearing potential, has a negative urine pregnancy test at Screening and willing to use acceptable methods of contraception (birth control pills, barriers) or abstinence throughout the Study 8. Subject is able and willing to comply with Study procedures including the use of an off-loading device (as applicable for the location of the ulcer) and adhere to protocol during the Study in the opinion of Investigator 9. A Subject or LAR agrees to sign informed consent form and allow audio visual recording of consent, if applicable
Exclusion criteria
1. Actively infected ulcers with or without purulent discharge, ulcers with exposed bone or associated with osteomyelitis 2. Subjects with more than three ulcers below knee 3. Subjects with Target Ulcer requiring off-loading that cannot be effectively off-loaded; or unable to tolerate the off-loading method 4. Subject has ulcers caused by a disease other than diabetes, e.g., fungal ulcerations, malignant ulcerations, and ulcerations due to venous or arterial insufficiency, or due to hematological disorders, in the opinion of the Investigator 5. Ulcer, about which the Investigator is suspicious for cancer 6. Subjects with a gangrenous or ischemic ulcer 7. Subject with ulcer that in the opinion of the Investigator, may need amputation 8. Subject with Target ulcer where wound measurement is not possible, such as ulcers between toes 9. Body mass index (BMI) \> 40 kg/m2 10. Laboratory values at Screening of: 1. Hemoglobin \< 10.0 g/dL 2. White Blood Cells (WBC) \< 2.0 X 109 cells/L 3. Liver function studies \[Total bilirubin, aspartate aminotransferase (AST) and alanine transaminase (ALT)\] \> 3x the upper limit of normal 4. Albumin \< 2.5 g/dL 5. eGFR \< 25 mL/min 11. Presence of any existing clinically significant medical condition(s) that, in the opinion of the Investigator, could interfere with wound healing 12. Subject has received or is currently receiving or scheduled to receive any medication or therapies during the course of the Study that will modulate wound healing 13. Subject with intolerance to β-blockers at any time in the past 14. Has any other factor which may, in the opinion of the Investigator, compromise participation and/or follow-up in the Study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Target Ulcer Closure Within 12-week Treatment Phase, as Assessed by Blinded Investigator | Wound closure assessed up to week 12 and confirmed by 2 visits 2 weeks apart; only participants with wound closure at or before Week 12 and who maintained closure after 4-weeks of follow-up reported | Proportion of complete closure of wounds within 12-week treatment phase where Complete wound closure is defined as complete skin re-epithelialization that is without drainage or dressing requirements evaluated in two visits two weeks apart from first observation of closure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Target Ulcer Closure Till End of Study, as Assessed by the Blinded Investigator. | 24-weeks. The ulcers achieving complete closure till end of study | Proportion of complete closure of wounds at 24-weeks or End of Study where Complete wound closure is defined as complete skin re-epithelialization that is without drainage or dressing requirements. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Treatment Emergent Adverse Events (TEAEs) | 24-weeks | Proportion of Treatment emergent adverse events (TEAEs) in all the groups |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Galnobax® 14% Gel Plus SoC Esmolol Hydrochloride gel (Galnobax) administered twice daily along with Standard of Care | 76 |
| SoC Only Only Standard of Care administered twice daily | 76 |
| Vehicle Plus SoC Vehicle gel administered twice daily along with Standard of Care | 24 |
| Total | 176 |
Baseline characteristics
| Characteristic | Galnobax® 14% Gel Plus SoC | SoC Only | Vehicle Plus SoC | Total |
|---|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 8.96 | 56.1 years STANDARD_DEVIATION 9.36 | 57.3 years STANDARD_DEVIATION 8.01 | 56.4 years STANDARD_DEVIATION 8.97 |
| Body Mass Index | 26.7 Kg/m2 STANDARD_DEVIATION 4.05 | 25.9 Kg/m2 STANDARD_DEVIATION 4.3 | 25.9 Kg/m2 STANDARD_DEVIATION 3.39 | 26.2 Kg/m2 STANDARD_DEVIATION 4.08 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment India | 76 participants | 76 participants | 24 participants | 176 participants |
| Sex: Female, Male Female | 21 Participants | 24 Participants | 9 Participants | 54 Participants |
| Sex: Female, Male Male | 55 Participants | 52 Participants | 15 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 76 | 1 / 24 |
| other Total, other adverse events | 9 / 76 | 7 / 76 | 9 / 24 |
| serious Total, serious adverse events | 1 / 76 | 2 / 76 | 4 / 24 |
Outcome results
Primary
Proportion of Subjects Achieving Target Ulcer Closure Within 12-week Treatment Phase, as Assessed by Blinded Investigator
Proportion of complete closure of wounds within 12-week treatment phase where Complete wound closure is defined as complete skin re-epithelialization that is without drainage or dressing requirements evaluated in two visits two weeks apart from first observation of closure.
Time frame: Wound closure assessed up to week 12 and confirmed by 2 visits 2 weeks apart; only participants with wound closure at or before Week 12 and who maintained closure after 4-weeks of follow-up reported
Population: Subjects in FAS population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Galnobax® 14% Gel Plus SoC | Proportion of Subjects Achieving Target Ulcer Closure Within 12-week Treatment Phase, as Assessed by Blinded Investigator | 41 Participants |
| SoC Only | Proportion of Subjects Achieving Target Ulcer Closure Within 12-week Treatment Phase, as Assessed by Blinded Investigator | 30 Participants |
| Vehicle Plus SoC | Proportion of Subjects Achieving Target Ulcer Closure Within 12-week Treatment Phase, as Assessed by Blinded Investigator | 10 Participants |
p-value: 0.027695% CI: [1.08, 4.17]Chi-squared
Secondary
Proportion of Subjects Achieving Target Ulcer Closure Till End of Study, as Assessed by the Blinded Investigator.
Proportion of complete closure of wounds at 24-weeks or End of Study where Complete wound closure is defined as complete skin re-epithelialization that is without drainage or dressing requirements.
Time frame: 24-weeks. The ulcers achieving complete closure till end of study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Galnobax® 14% Gel Plus SoC | Proportion of Subjects Achieving Target Ulcer Closure Till End of Study, as Assessed by the Blinded Investigator. | 44 Participants |
| SoC Only | Proportion of Subjects Achieving Target Ulcer Closure Till End of Study, as Assessed by the Blinded Investigator. | 35 Participants |
| Vehicle Plus SoC | Proportion of Subjects Achieving Target Ulcer Closure Till End of Study, as Assessed by the Blinded Investigator. | 9 Participants |
p-value: 0.012695% CI: [1.22, 5.99]Chi-squared
Other Pre-specified
Proportion of Subjects With Treatment Emergent Adverse Events (TEAEs)
Proportion of Treatment emergent adverse events (TEAEs) in all the groups
Time frame: 24-weeks
Population: ITT (Safety population)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Galnobax® 14% Gel Plus SoC | Proportion of Subjects With Treatment Emergent Adverse Events (TEAEs) | 10 Participants |
| SoC Only | Proportion of Subjects With Treatment Emergent Adverse Events (TEAEs) | 14 Participants |
| Vehicle Plus SoC | Proportion of Subjects With Treatment Emergent Adverse Events (TEAEs) | 9 Participants |