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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Foot Ulcers
• Intervention / Treatment: Drug: Selinexor; Other: Standard-of-Care; Other: Vehicle 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 Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 0610
    • South Pacific Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Selinexor; Topical gel; Other Names: KPT-330; Other: Standard-of-Care; Surgical debridement, sterile saline rinses, and dressing changes.; Other Names: SOC; Other: Vehicle Gel; Topical vehicle gel with no active ingredients.
Experimental: 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.	Drug: Selinexor; Topical gel; Other Names: KPT-330; Other: Standard-of-Care; Surgical debridement, sterile saline rinses, and dressing changes.; Other Names: SOC; Other: Vehicle Gel; Topical vehicle gel with no active ingredients.
Experimental: 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.	Drug: Selinexor; Topical gel; Other Names: KPT-330; Other: Standard-of-Care; Surgical debridement, sterile saline rinses, and dressing changes.; Other Names: SOC; Other: Vehicle Gel; Topical vehicle gel with no active ingredients.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Karyopharm Therapeutics Inc

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: February 19, 2015
• First Posted (Estimate): February 20, 2015

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; DFU; Foot Ulcers; Karyopharm; KPT-330; Selinexor
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: KCP-330-501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes