ANZCTR - Registration

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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]

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)

Condition category

Condition code

Skin

Dermatological conditions

Metabolic and Endocrine

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]

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]

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]

After 12 weeks of treatment.

Secondary outcome [1]

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]

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]

To determine and compare preliminary efficacy of selinexor gel. This will be assessed through examining ulcer size and depth.

Timepoint [2]

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?

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

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Karyopharm Therapeutics Inc.

Address [1]

85 Wells Avenue
Newton, MA 02459 USA

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Commercial sector/Industry

Name [1]

Novotech (Australia Pty Ltd

Address [1]

Level 3, 235 Pyrmont Street
Pyrmont NSW 2009

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Health and Disability Ethics Committee New Zealand

Ethics committee address [1]

Ministry of Health
Ethics Department
20 Aitken Street
WELLINGTON 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

06/11/2014

Approval date [1]

24/11/2014

Ethics approval number [1]

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

Dr Edward Watson

Address

South Pacific Clinical Trials
382 Te Atatu Road,
Te Atatu Peninsula
Auckland 0610

Country

New Zealand

Phone

+ 64 9 8340015

Fax

edward.watson@southpactrials.com

Contact person for public queries

Name

Christine Kitsos

Address

Karyopharm Therapeutics
85 Wells Avenue
Newton, MA 02459

Country

United States of America

Phone

+1 617-658-0527

Fax

+ 1 617-224-9420

Christine@karyopharm.com

Contact person for scientific queries

Name

Hagop Youssoufian

Address

Karyopharm Therapeutics
85 Wells Avenue
Newton, MA 02459

Country

United States of America

Phone

+ 1 617-658-0534

Fax

+ 1 617-224-9420

Hagop@karyopharm.com

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

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No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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