Chronic Cutaneous Ulcer, Sickle Cell Disease
Conditions
Keywords
chronic sickle cell leg ulcer
Brief summary
Approximately 60 subjects will be enrolled into this double-blind, placebo-controlled study for the Deferoxamine Intradermal Delivery Patch (DIDP). Those subjects who pass Screening will enter into the 2-week Standard of Care (SOC) Run-In period. During this time, ulcers will be assessed to check healing based on digital planimetry, and qualitative features of the ulcer. Subjects who meet eligibility criteria at the end of the 2-week Run-in Period will be randomized into active and control groups (2 active to 1 placebo) and enter the 12-week Treatment Period. At each visit during the Treatment Period, the target ulcer will be measured by digital photographic planimetry, the Principal Investigator will assess the wound qualitative attributes, and the DIDP (or placebo patch) will be placed as the primary wound dressing. At each visit the subject will also receive/review a daily diary to document pain , study drug compliance, and analgesic use.
Detailed description
Approximately 60 subjects will be enrolled to allow for up to 48 male or female subjects with SCD and cutaneous ulcers to complete this double-blind, placebo-controlled study. A sentinel group of 3 subjects will be enrolled and evaluated for safety (while still blinded). The remaining subjects will be enrolled in a 2:1 ratio, active:placebo. Those subjects who pass Screening will enter into the Standard of Care (SOC) Run-In period. During this time, ulcers will be assessed to check healing based on digital planimetry, and qualitative features of the ulcer. Subjects who meet eligibility criteria at the end of the Run-in Period will be randomized and enter the 12-week Treatment Period. The DIDP (or placebo) will be replaced daily at home. The subject will visit the clinic on an approximately weekly basis for study assessments, to include imaging and planimetric wound measurements and qualitative wound assessments. Clinical laboratory samples will be collected at Treatment Baseline, Treatment Weeks 4, 8 and 12, or at End of Study (EOS) visit if sooner. A blood sample for PK testing will also be collected at these timepoints. During this Treatment Period, if at any time the wound has met the criterion for 100% healing, the subject will immediately go into the 4-week Follow-up Period. During the Follow-up Period, the subject will come to the clinic at 1-week intervals. At these visits, the area of the wound will continue to be protected with a protective dressing. Clinical laboratory samples will be collected at the Termination Visit. Ulcer pain will be assessed by the subject daily and recorded in a diary, along with a record of analgesic use. At each visit, study staff will assist the subjects to assign an overall ulcer pain score for the week. Quality of Life Assessment will be performed at Baseline prior to dosing and at End of Treatment. Safety will be assessed based upon known adverse outcomes of Deferoxamine (DFO) therapy. Skin will be examined for evidence of rash and skin irritation.
Interventions
DRUGDeferoxamine Product
Deferoxamine Intradermal Delivery Patch
OTHERPlacebo
Placebo Patch
Sponsors
TauTona Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, \>18 years of age 2. Diagnosed with Sickle Cell Disease (SS, SC, Sß-thalassemia, SD, SOArab) 3. Cutaneous ulcer with a University of Texas Wound Classification System Grade 1A or 2A (= Wagner class 1or 2, without infection or ischemia) 4. Ulcer on lower leg, ankle, or dorsum of foot 5. Vascular status of site assessed and judged adequate for healing (per Section 4.2) 6. Ulcer present ≥ 14 days but not \> 6 months at time of screening 7. Ulcer 2.0 cm2 to 45.0 cm2 and \< 6.0 cm diameter at widest point after debridement, prior to randomization. 8. Ulcer healed by \< 25% during the SOC run-in period prior to Visit 4 randomization. 9. Subject is willing to use acceptable form of birth control (per Section 4.2) during trial and for one month thereafter
Exclusion criteria
1. Active infection/purulence at ulcer site, based on Investigator's clinical judgement 2. Current or history of osteomyelitis at or near site of ulcer 3. Serum albumin \< 2.0 g/dL 4. Treatment with systemic DFO within 7 days of study entry 5. Serum ferritin \> 1000 ng/mL 6. Subjects requiring, or expected to require, iron chelation therapy (systemic deferoxamine, deferasirox, or deferiprone) during the duration of the study. 7. Subjects on dialysis or with evidence of nephrotic syndrome. 8. Known bleeding or coagulation disorder that would preclude surgical debridement, as necessary. 9. The subject has a major uncontrolled medical disorder, such as serious cardiovascular, renal, liver, pulmonary disease, or pulmonary disease (per Investigator discretion). 10. Any condition that in the Investigator's opinion would warrant exclusion from the study or prevent the subject from completing the study 11. Previous participation in another clinical trial within 30 days prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety / Tolerability] | 12 weeks | Incidence of systemic and local adverse events of DIDP applied to non-healing cutaneous leg ulcers. Changes from baseline characteristics that are treatment-related as measured by physical examinations, clinical laboratory, skin and other physiologic assessments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial wound closure incidence | 12 weeks | Incidence of 80% closure |
| Degree of Wound closure | 12 weeks | Percentage of wound closure |
| Total wound closure incidence | 12 weeks | Incidence of 100% closure |
| Wound closure rate | 12 weeks | rate of closure |
| Ulcer recurrence | 4 week follow-up post | Incidence |
Other
| Measure | Time frame | Description |
|---|---|---|
| QOL: Health-related QOL in Chronic Wounds | 12 weeks | Wound QOL: Health-related QOL in Chronic Wounds (Augustin et el, 2014; Blome et al, 2014) Response range: not at all -to- very much |
| Pharmacokinetics (blood) | 12 weeks | Deferoxamine / Placebo Peak plasma concentration (Cmax) |
| Analgesic use | 12 weeks | Diary: Opioid analgesic use converted as morphine mg equivalents (MME). Non-steroidal use will be descriptive. |
| Ulcer pain: Numeric Pain Rating Scale | 12 weeks | Numeric Pain Rating Scale (McCaffery et al, 1989) Scale: 0-10 (0 = no pain, 10 = severe pain) |
Countries
United States
Outcome results
None listed