Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001260617
Ethics application status
Approved
Date submitted
19/11/2014
Date registered
3/12/2014
Date last updated
1/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Trial of Topical Selinexor (KPT-330) in Patients with Diabetic Foot Ulcers (DFU)
Scientific title
A Phase 1/2, Multi-Dose, Evaluator-Blinded, Randomized, Vehicle- and Standard of Care-Controlled Dose-Escalation Study to Assess Safety, Tolerability, and Pharmacokinetics of Topical Selinexor (KPT-330) in Patients with Diabetic Foot Ulcers (DFU)
Secondary ID [1] 285697 0
KCP-330-501
Universal Trial Number (UTN)
U111111633326
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Foot Ulcers (DFU) 293554 0
Condition category
Condition code
Skin 293839 293839 0 0
Dermatological conditions
Metabolic and Endocrine 293916 293916 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will receive standard of care (SOC) treatment for their DFU. SOC treatment will include surgical debridement of the ulcer, saline rinses and dressing changes.

Participants will be enrolled into one of three treatment cohorts. There will be approximately 10 participants per cohort group. In each cohort, 6 of the 10 participants will receive one of the following topical selinexor gel concentrations (10 micromolar, 30 micromolar or 70 micromolar). About 2mL of gel will be applied to a DFU twice per week for 12 weeks. All participants in the first cohort group must have completed at least 4 weeks of treatment before the next cohort group starts.

Participants will be asked to return the syringes of topical selinexor gel (used and unused) at each study visit to monitor use of the topical gel. The participants will also complete a diary to record the dates and times of topical gel application.
Intervention code [1] 290639 0
Treatment: Drugs
Comparator / control treatment
There are two control groups:
1. Standard of care (SOC) only group. SOC treatment will include surgical debridement of the ulcer, saline rinses and dressing changes.
2. SOC with vehicle gel. Some participants will receive SOC and vehicle gel (gel without the active ingredient selinexor).
Control group
Placebo

Outcomes
Primary outcome [1] 293619 0
To determine and compare the safety and tolerability of selinexor gel This will be assessed through adverse events, local skin reactions and wound assessment.
Timepoint [1] 293619 0
After 12 weeks of treatment.
Secondary outcome [1] 311480 0
To determine to pharmacokinetic profile of selinexor gel.
This will be assessed through blood draws on Day 1, 28 and 77 collected at times 0, 15, 30 minutes, 1, 2, 4, 6, 8, 24 hours after study drug application.
Timepoint [1] 311480 0
Day 1, 28 and 77 collected at times 0, 15, 30 minutes, 1, 2, 4, 6, 8, 24 hours after study drug application
Secondary outcome [2] 311488 0
To determine and compare preliminary efficacy of selinexor gel. This will be assessed through examining ulcer size and depth.
Timepoint [2] 311488 0
After 12 weeks of treatment

Eligibility
Key inclusion criteria
Patient is male or female 18-80 years old
Patients with diabetes (Type I or Type II)
Women of childbearing potential must have a negative urine pregnancy test and must agree to an effective method of contraception..
Male patients who are sexually active with female partners who are of childbearing potential must agree to use an effective method of contraception
Up to two anatomically discrete DFU that are non-healing but have persisted for less than or equal to 12 months
Adequate arterial supply to the affected limb
Inability to perceive 10 grams of pressure in the affected limb
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient is pregnant, lactating, or is planning to become pregnant during the study.
Patient is currently enrolled in an investigational drug or device study or has used an investigational drug or investigational device treatment within 30 days prior Patient has a foot ulcer that is clearly of non-diabetic pathophysiology.
More than 2 DFU’s on the target limb
DFU on the heel
Clinically infected DFU
Active osteomyelitis or uncontrolled connective tissue disease
Active malignancy
Active systemic infection
Active Charcot foot or other structural deformity within 6 months
Positive for HIV or Hepatitis
Significant sickle-cell anemia or peripheral vascular disease
Diabetic neuropathy (Grade 3 or Grade 2 with significant pain)
End stage renal failure
Poor nutritional status
Any laboratory values collected in the study that is 2 times the upper limit of normal
Revascularisation surgery within last 8 weeks
Non-surgical peripheral revascularization within 4 weeks
Recent surgery to affected foot within 8 weeks
Radiation therapy to affected foot
Systemic antibiotics, corticosteroids, supplemental vitamin E, chemotherapeutic agents, immunosuppressive drugs, antivirals angiogenesis inhibitors 2 weeks prior.
Dermal substitute or living skin equivalent 30 days prior
Autologous growth factor therapy 30 days prior
Vacuum assisted closure, hyperbaric oxygen or other non-drug DFU therapy within 30 days
Sensitivity to ingredients in study drug
History of drug or alcohol abuse within 6 months

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible participants will be assigned to a sequential treatment cohort with selinexor gel or vehicle gel. Randomisation will be performed via a central web-based randomisation system (Interactive Web Response System [IWRS]). Only certain 'unblinded' site staff will know the allocation assignment.

Blocked randomization will be performed such that a 3:1:1 allocation of patients to SOC + selinexor gel, SOC + vehicle gel, or SOC alone will be maintained.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomized via an Interactive Web Response System (IWRS) at Visit 1/Day 1. Blocked randomization will be performed, such that a 3:1:1 allocation of patients to SOC + selinexor gel, SOC + vehicle gel, or SOC alone will be maintained. Randomization will be performed centrally without regard to study site and the randomization will therefore proceed sequentially based on the order of enrolment and the sequence of randomization numbers in the centralized list. No patients will be replaced and once a randomization number and assignment have been used, there will be no replacement.
Note that the randomization list will be created in SAS and treatment codes are generated using a permuted block design utilizing PROC PLAN of SAS, where random allocation occurs within each block sequence.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Nil
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All randomized patients who received and applied test article at least once will be included in the analysis of safety and efficacy. Summary tables will be provided for baseline variables, efficacy variables, and safety variables for each treatment group. Continuous variables will be described by descriptive statistics (n, mean, median, standard deviation,
minimum, and maximum, as well as two-sided 95% confidence intervals. Frequency counts and percentage of patients within each category will be provided for categorical data.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
15/12/2014
Actual
Date of last participant enrolment
Anticipated
30/10/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment outside Australia
Country [1] 6484 0
New Zealand
State/province [1] 6484 0
Auckland

Funding & Sponsors
Funding source category [1] 290268 0
Commercial sector/Industry
Name [1] 290268 0
Karyopharm Therapeutics Inc.
Country [1] 290268 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Karyopharm Therapeutics Inc.
Address
85 Wells Avenue
Newton, MA 02459 USA
Country
United States of America
Secondary sponsor category [1] 288984 0
None
Name [1] 288984 0
Address [1] 288984 0
Country [1] 288984 0
Other collaborator category [1] 278237 0
Commercial sector/Industry
Name [1] 278237 0
Novotech (Australia Pty Ltd
Address [1] 278237 0
Level 3, 235 Pyrmont Street
Pyrmont NSW 2009
Country [1] 278237 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291964 0
Health and Disability Ethics Committee New Zealand
Ethics committee address [1] 291964 0
Ministry of Health
Ethics Department
20 Aitken Street
WELLINGTON 6011
Ethics committee country [1] 291964 0
New Zealand
Date submitted for ethics approval [1] 291964 0
06/11/2014
Approval date [1] 291964 0
24/11/2014
Ethics approval number [1] 291964 0

Summary
Brief summary
The purpose of this research study is to see if topical (applied to the skin) selinexor has any effects towards the healing of diabetic foot ulcer(s). In non-healing diabetic foot ulcers, the wound healing process does not work properly and the ulcer is locked into a state of continued inflammation. While there are other factors that contribute to the failure of the wound to heal, controlling the state of inflammation would be beneficial for wound healing. Inflammation is controlled by multiple mechanisms within human cells. One way inflammation continues uncontrolled is when cells get rid of certain “anti-inflammatory” proteins that would normally reduce inflammation.

The study drug selinexor works by trapping “anti-inflammatory proteins” within the cell, reducing inflammation so that the wound can begin to heal.

Oral selinexor has previously been tested in humans to define a safe dose to be administered. The dose to be used in the topical form is more than 23,000 times lower than the oral form. This study will examine the effects of selinexor on diabetic foot ulcer(s) including any side-effects.

Participation in this study could be up to 7 months involving 24 visits. Following informed consent participants enter a screening phase which includes medical history taking, physical exam, measuring vital signs & weight, eye examination, limb sensation and blood flow testing, photographs taken of the wound, electrocardiogram, blood and urine samples will be collected for standard laboratory testing. Participants will be provided instructions on how to treat their DFU. Participants will be provided with a diary and instructions on how to complete it. After the screening phase, eligible participants will be randomized to a treatment group within a sequential dose cohort. During the treatment period (up of 12 weeks) all participants will receive standard of care plus selinexor, vehicle gel or standard of care alone. Assessments will include the same done in the screening phase and additional blood samples collected for pharmacokinetic testing. After the treatment phase, participants will be asked to attend an end of treatment visit where assessments described in the treatment phase will be repeated. Finally there will be 3 follow up visits and 2 follow up phone calls over 12 weeks for those participants who have complete wound closure at the end of the treatment phase.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52882 0
Dr Edward Watson
Address 52882 0
South Pacific Clinical Trials
382 Te Atatu Road,
Te Atatu Peninsula
Auckland 0610
Country 52882 0
New Zealand
Phone 52882 0
+ 64 9 8340015
Fax 52882 0
Email 52882 0
[email protected]
Contact person for public queries
Name 52883 0
Ms Christine Kitsos
Address 52883 0
Karyopharm Therapeutics
85 Wells Avenue
Newton, MA 02459
Country 52883 0
United States of America
Phone 52883 0
+1 617-658-0527
Fax 52883 0
+ 1 617-224-9420
Email 52883 0
[email protected]
Contact person for scientific queries
Name 52884 0
Mr Hagop Youssoufian
Address 52884 0
Karyopharm Therapeutics
85 Wells Avenue
Newton, MA 02459
Country 52884 0
United States of America
Phone 52884 0
+ 1 617-658-0534
Fax 52884 0
+ 1 617-224-9420
Email 52884 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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