Study of Safety, Tolerability, and Pharmacokinetics of Topical Selinexor (KPT-330) Diabetic Foot Ulcer (DFU) Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Diabetic Foot Ulcers

Intervention / Treatment
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* Drug: Selinexor
* Other: Standard-of-Care
* Other: Vehicle Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has a clinical diagnosis of Type I or Type II diabetes mellitus with an HbA1c ≤ 10.0 and has a BMI ≤40. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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. | Drug: Selinexor<br>* Topical gel<br>* Other names: KPT-330;Other: Standard-of-Care<br>* Surgical debridement, sterile saline rinses, and dressing changes.<br>* Other names: SOC;Other: Vehicle Gel<br>* Topical vehicle gel with no active ingredients.<br>|
| Experimental: Cohort 2<br>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. | Drug: Selinexor<br>* Topical gel<br>* Other names: KPT-330;Other: Standard-of-Care<br>* Surgical debridement, sterile saline rinses, and dressing changes.<br>* Other names: SOC;Other: Vehicle Gel<br>* Topical vehicle gel with no active ingredients.<br>|
| Experimental: Cohort 3<br>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. | Drug: Selinexor<br>* Topical gel<br>* Other names: KPT-330;Other: Standard-of-Care<br>* Surgical debridement, sterile saline rinses, and dressing changes.<br>* Other names: SOC;Other: Vehicle Gel<br>* Topical vehicle gel with no active ingredients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of Local Skin Reactions (LSR) | 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. | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ulcer Closure | Proportion of patients in each treatment group with complete ulcer closure of the target diabetic foot ulcer. | 84 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Foot Ulcers, DFU, KPT-330, Selinexor, Karyopharm