Phase 1/2, Multi-Dose, Evaluator-Blinded, Randomized, Vehicle & Standard Of Care-Controlled Dose-Escalation Study To Assess Safety, Tolerability, Pharmacokinetics Of Topical Selinexor In Patients With Diabetic Foot Ulcers
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Sponsor
- Karyopharm Therapeutics Inc
- Locations
- 1
- Primary Endpoint
- Presence of Local Skin Reactions (LSR)
Study Overview
Brief Summary
Patients with eligible diabetic foot ulcers will be screened, treated, and followed for complete ulcer closure. This is a randomized trial. All patients will receive standard-of-care treatment. Additionally, some patients will receive treatment with topical Selinexor gel and some will receive topical placebo gel.
Detailed Description
Approximately 30 patients who meet the eligibility criteria will be enrolled. Eligible patients with diabetic foot ulcers will be screened, randomized, treated, and followed for complete ulcer closure.
After screening, qualified patients will be treated for up to 12 weeks. Patients who achieve complete ulcer closure will be followed for an additional 12 weeks.
All patients will receive standard-of-care treatment. After randomization some patients will be treated with topical Selinexor gel twice weekly and some patients will be treated with a topical placebo gel twice weekly. Patients receiving Selinexor will be assigned to a sequential treatment cohort, either a 10 μM (μmol/L), 30 μM, or 70 μM dose.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient has a clinical diagnosis of Type I or Type II diabetes mellitus with an HbA1c ≤ 10.0 and has a BMI ≤
- •The DFU(s) to be treated must be:
- •Anatomically discrete,
- •Non-healing, but has persisted for ≤12 months
- •Measures 1 cm2 ≤ area ≤ 5 cm2 following debridement,
- •Has a Wagner Grade 1 (i.e., not involving bone, muscle, tendons, or ligaments),
- •The Target DFU is located distal to the ankle (i.e., below the malleolus), and
- •Is able to be adequately off-loaded.
- •The patient has adequate arterial blood supply in the affected limb at screening.
- •Patient has the inability to perceive 10 grams pressure in the peri-ulcer area and other regions of the affected foot and toes using Semmes-Weinstein 5.07 monofilament at screening.
Exclusion Criteria
- •Patient has a foot ulcer that is clearly of non-diabetic pathophysiology.
- •Patient has more than two (2) DFUs on the target lower extremity.
- •DFU is clinically infected.
- •Patient has active osteomyelitis of the foot or active, uncontrolled, connective tissue disease
Arms & Interventions
Cohort 1
Cohort 1 will be randomized to one of the following treatment groups:
a) Standard-of-care (SOC) + Selinexor gel, 10 μM
, b) SOC + vehicle gel c) SOC alone.
Intervention: Selinexor (Drug)
Cohort 1
Cohort 1 will be randomized to one of the following treatment groups:
a) Standard-of-care (SOC) + Selinexor gel, 10 μM
, b) SOC + vehicle gel c) SOC alone.
Intervention: Standard-of-Care (Other)
Cohort 1
Cohort 1 will be randomized to one of the following treatment groups:
a) Standard-of-care (SOC) + Selinexor gel, 10 μM
, b) SOC + vehicle gel c) SOC alone.
Intervention: Vehicle Gel (Other)
Cohort 2
Cohort 2 will be randomized to one of the following treatment groups:
- Standard-of-care (SOC) + Selinexor gel, 30 μM
- SOC + vehicle gel
- SOC alone.
Intervention: Selinexor (Drug)
Cohort 2
Cohort 2 will be randomized to one of the following treatment groups:
- Standard-of-care (SOC) + Selinexor gel, 30 μM
- SOC + vehicle gel
- SOC alone.
Intervention: Standard-of-Care (Other)
Cohort 2
Cohort 2 will be randomized to one of the following treatment groups:
- Standard-of-care (SOC) + Selinexor gel, 30 μM
- SOC + vehicle gel
- SOC alone.
Intervention: Vehicle Gel (Other)
Cohort 3
Cohort 3 will be randomized to one of the following treatment groups:
- Standard-of-care (SOC) + Selinexor gel, 70 μM
- SOC + vehicle gel
- SOC alone.
Intervention: Selinexor (Drug)
Cohort 3
Cohort 3 will be randomized to one of the following treatment groups:
- Standard-of-care (SOC) + Selinexor gel, 70 μM
- SOC + vehicle gel
- SOC alone.
Intervention: Standard-of-Care (Other)
Cohort 3
Cohort 3 will be randomized to one of the following treatment groups:
- Standard-of-care (SOC) + Selinexor gel, 70 μM
- SOC + vehicle gel
- SOC alone.
Intervention: Vehicle Gel (Other)
Outcomes
Primary Outcomes
Presence of Local Skin Reactions (LSR)
Time Frame: 84 days
Presence of local skin reactions (erythema, edema, pain, tenderness, induration, swelling, wound drainage, purulence, odor, cellulitis, callus, and maceration) within 4 cm of the diabetic foot ulcer wound edge.
Secondary Outcomes
- Ulcer Closure(84 days)