E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Foot Ulcers - patients with diabetes mellitus who have a chronic Wagner Grade 1 or 2 Plantar neuropathic foot ulcer, 0.75 to 6.0 sq cms in size |
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E.1.1.1 | Medical condition in easily understood language |
Foot Ulcers in Patients with Diabetes- Patients should have had a foot ulcer for more than a month and less than a year in duration |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012664 |
E.1.2 | Term | Diabetic foot ulcer |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective The primary objective of the study is to demonstrate the increased incidence of complete wound closure by 10 weeks confirmed 2 weeks later by Aclerastide (DSC127) compared to the vehicle in subjects with diabetes mellitus (DM) who have chronic Wagner Grade 1 or 2 plantar neuropathic foot ulcers, 0.75 - 6 cm2 in size. Complete wound closure is defined as complete skin re-epithelialization without drainage or dressing requirements. Complete closure will be confirmed at a study visit 2 weeks later.
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives The secondary objectives of the study are: ● To demonstrate the increased incidence of complete wound closure by 10 weeks confirmed 2 weeks later by Aclerastide (DSC127) compared to the Standard of Care (SOC) gel (AQUASITE®) in subjects with DM who have chronic Wagner Grade 1 or 2 plantar neuropathic foot ulcers, 0.75 - 6 cm2 in size. ● To assess the similarity of response between vehicle and SOC gel for incidence of complete wound closure up to 10 weeks, confirmed 2 weeks later, in subjects with DM who have chronic Wagner Grade 1 or 2 plantar neuropathic foot ulcers, 0.75 - 6 cm2 in size.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject who meets all the following criteria will be included in the study: 1. Male or female ambulatory subject age ≥18 years at the time of informed consent. 2. Has type 1 or type 2 DM under metabolic control as confirmed by a glycosylated hemoglobin (HbA1c) of ≤12% and a serum creatinine level of ≤3mg/dL. 3. At Screening and at Baseline (prior to randomization), subject has at least ulcer that fulfills all of the following criteria: a) present for ≥1 month and ≤ 1year. b) Partial- or full- thickness and not involving bone, tendon, or capsule (probing to tendon or capsule), i.e., Wagner Grade 1 or 2. c) Has no sign of infection or osteomyelitis d) Plantar neuropathic ulcer - The ulcer must predominately be on the plantar surface (i.e., weight bearing) of the foot to ensure adequate off-loading, and may include the toes but edges of the ulcer may be extended to the sides of the foot. e) Size of the target ulcer must be 0.75 - 6 cm.2 f) Target ulcer must be non-healing as defined as <30% reduction in size in response to Standard of Care during the two-week Screening Period. o If more than one ulcer is present that meets the Inclusion Criteria, the largest one meeting all criteria will be considered the target ulcer. o If there are two ulcers the same size that meet all criteria the one with the higher Wagner Grade will be considered the target ulcer. o If there are two ulcers of the same size and same Wagner Grade, the one present for the longest (qualifying) time will be considered the target ulcer. o Non-target ulcers will also be treated according to Standard of Care (Charcot Neuroarthropathy of the foot with the target ulcer must be excluded). 4. Has an ankle brachial index (ABI) >0.7 on the leg of the foot with the target ulcer. 5. Has an assessment of the baseline level of neuropathy of the foot using Semmes-Weinstein filaments. A subject will be considered to have site-specific neuropathy sufficient for loss of protective sensation (LOPS) if he/she is unable to feel a 5.07 Semmes-Weinstein monofilament in at least five of the following seven sites on the study foot: o Plantar to toes and metatarsals 1, 3, and 5 (three sites). o Plantar to midfoot medial and lateral (two sites). o Plantar heel (one site). o Dorsal distal first interspace (one site). 6. A female subject of childbearing potential must have a negative serum pregnancy test at the time of Screening. 7. A female subject of childbearing potential must be willing to use a medically acceptable method of birth control, such as Essure®, hormonal contraception (oral pills, implantable device, or skin patch), intrauterine device, tubal ligation, or double barrier throughout the study. A female subject of childbearing potential who practices abstinence is not required to employ birth control. 8. Has the ability and willingness to understand and comply with study procedures and to give written informed consent prior to enrollment in the study or initiation of study procedures.
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E.4 | Principal exclusion criteria |
A subject satisfying any of the following criteria will be excluded from participating in the study: 1. Has a known hypersensitivity to any of the investigational drug or vehicle components. 2. Has been exposed to any investigational agent within 30 days of entry into the study. 3. A female who is pregnant or nursing. 4. Has active malignant disease of any kind except for basal cell carcinoma (of the skin). A subject, who has had a malignant disease in the past, was treated and is currently disease-free, may be considered for study entry. 5. Has a hemoglobin of less than 8.5 gm/dL. 6. Transaminase levels greater than 3x normal. 7. Is receiving hemodialysis or chronic ambulatory peritoneal dialysis (CAPD) therapy. 8. Has had prior radiation therapy of any part of the foot with the target ulcer under study. 9. Use of systemic corticosteroids or immunosuppressants (within the 8 weeks prior to screening). 10. Has an ulcer primarily ischemic in etiology as diagnosed by an ABI of <0.7 on the affected extremity or great toe systolic pressure <50 mmHg or a transcutaneous oxygen pressure (TcPO2) <40 mmHg in the supine position and <40 mmHg while sitting, measured on the forefoot with electrode set at 44 C on the affected foot.
11. Has sickle-cell anemia, Reynaud's, or other peripheral vascular disease.
12. Has received a biologic agent to include growth factors and skin equivalents (Regranex®, Apligraft, or Dermagraft), in the past 30 days.
13. Has a target ulcer which is determined to be clinically infected and requires antimicrobials. Any antibiotic therapy must be completed or discontinued at screening.
14. Has a Wagner Grade 3 or greater DFU, deep abscess, or gangrene.
15. Has uncontrolled hypertension, in the opinion of the Investigator.
16. Any other finding, which in the opinion of the Investigator, may interfere with the assessment of the product or participation of the subject in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary and Secondary Objective Assessments: • The proportion of subjects with a target ulcer which achieves complete wound closure (skin re-epithelialization without drainage or dressing requirements) by 10 weeks (confirmed at a study visit 2 weeks later) after initiation of investigational product application.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis, the proportion of subjects with confirmed complete wound closure by 12 weeks, will be analyzed using a mixed methods logistic regression model which will include the stratification factors of ulcer size at Baseline, and ulcer grade as well as the covariates of duration of target ulcer and subject age. Study sites (pooled) will be treated as a random effect to account for possible correlation between subjects within a site. |
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E.5.2 | Secondary end point(s) |
The efficacy analyses will address the issue of controlling the error rate for the comparison of Aclerastide (DSC127) 0.03% to each of the controls using the Gatekeeping approach, where Aclerastide (DSC127) 0.03% is compared first to the vehicle group which gate-keeps for the comparison of Aclerastide (DSC127) 0.03% to the standard of care, thus maintaining the alpha at 0.05 (two-tailed). Between control group (vehicle and standard of care) comparisons will also be performed as part of the descriptive summary of results. The analysis for the primary and secondary objectives, the proportion of subjects with confirmed complete wound closure by 12 weeks, will be analyzed using a mixed methods logistic regression model which will include the stratification factors of ulcer size at Baseline and ulcer grade as well as, study site and the covariates of duration of target ulcer and subject age. Study sites (pooled) will be treated as a random effect to account for possible correlation between subjects within a site.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Time to the visit where the target ulcer achieves confirmed complete wound closure occurs (skin re-epithelialization without drainage or dressing requirements confirmed at a study visit 2 weeks later) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
South Africa |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 22 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 22 |