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Trial registered on ANZCTR


Registration number
ACTRN12617001178336
Ethics application status
Approved
Date submitted
8/08/2017
Date registered
10/08/2017
Date last updated
8/01/2019
Date data sharing statement initially provided
8/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Topical SM04755 Solution Following Topical Administration to Subjects with Mild to Moderate Plaque Psoriasis
Scientific title
A Phase 1, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Topical SM04755 Solution Following Topical Administration to Subjects with Mild to Moderate Plaque Psoriasis
Secondary ID [1] 292207 0
Nil
Universal Trial Number (UTN)
There is no UTN number for this study.
Trial acronym
None
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Plaque psoriasis 303696 0
Condition category
Condition code
Skin 303067 303067 0 0
Dermatological conditions
Inflammatory and Immune System 303677 303677 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase I, randomised double-blind placebo controlled, multiple ascending-dose (MAD) safety study of topical SM04755 in subjects with mild to moderate plaque psoriasis.

This is the first study in humans where multiple doses of topical SM04755 will be given to subjects with the health condition of plaque psoriasis.

SM04755 will be supplied for daily use as a single-use topical solution formulation containing SM04755 in water, benzyl alcohol, propylene glycol, hydroxypropyl methylcellulose and FD&C yellow #6. Subjects will receive 28 days of daily drug administration and will be followed for approximately 28 days after last treatment.

The participant will apply 0.8mL solution topically to the target plaque lesion..

Dose escalation levels will be 15, 45 and 90 mg SM04755 per mL. Some subjects at each dose level will also receive placebo. During dose-escalation, subjects will receive either SM04755 or placebo.. The dose of SM04755 will be escalated in successive cohorts.

Safety data for each cohort will be reviewed by the Safety Review Committee (SRC) prior to escalation to the next cohort and immediately following any Dose Limiting Toxicity (DLT).

If 4 or more subjects in the active group experience a DLT at any dose level, no further subjects will be started at that dose, nor will higher doses be started. The MTD is defined as the highest dose level at which, of the 16 subjects enrolled in that dose cohort, less than 4 subjects in the active group develop a DLT.

Compliance to the study protocol, applicable regulatory requirements and investigator's obligations will be monitored by Datapharm Australia Pty Ltd on behalf of the sponsor according to ICH GCP guidelines and standard operation procedures. All electronic clinical record forms will by 100% source verified against corresponding source documentation for each subject and includes but not limited to drug accountability and preparation procedures, appropriate consenting procedures and adherence to dosing procedures. At-site monitoring will be carried out according to the schedule outlined in the monitoring plan and includes for cause visits if need arises.
Intervention code [1] 298363 0
Treatment: Drugs
Comparator / control treatment
Placebo (the same solution as the active but without the drug product)
Control group
Placebo

Outcomes
Primary outcome [1] 302794 0
Safety and tolerability of topical SM04755 solution applied topically once daily for 28 days as measured by adverse events (AEs), electrocardiogram (ECG), physical examinations, clinical laboratory tests (non-fasting) and vital signs (height, weight, pulse, blood pressure, respiratory rate, and temperature).
Timepoint [1] 302794 0
AEs are assessed everyday from Day 1 through end of study Day 56 (or through the observation period of ongoing AEs)

ECG measurements taken on:
Screening Visit
Days 1 and 28 (pre and post study drug administration)
Days 2, 29, 42 and 56 after intervention commencement
or early termination

Physical Examination performed on:
Screening Visit
Days 1 and 28 (pre drug administration only)
Days 2, 7, 14, 21, 29, 42 and 56 after intervention commencement
or early termination

Clinical Laboratory test samples taken on::
Screening Visit
Days 7, 14, 21, 28, 42, and 56 after intervention commencement
or early termination

Vital sign measurements taken at:
Screening Visit
Days 1, and 28 (pre and post drug administration)
Days 2, 7, 14, 21, 29, 42 and 56 after intervention commencement
or early termination
Primary outcome [2] 302890 0
Incidence of dose limiting toxicities (DLTs).

A DLT is defined as one of the following if considered related to study medication by the Investigator:
- Serious adverse event (SAE)
- Any SAE not clearly attributable to another cause
- A healthy skin score of 3 or 4 (any category)
- A target plaque skin score of 3 or 4 (burning/stinging category only)
Timepoint [2] 302890 0
Every day from Day 1 post study drug administration through to end of study Day 56
Primary outcome [3] 302891 0
Plasma PK parameter estimates of SM04755 on Days 1, 2, 7, 14, 28 and 29.

The following PK parameters will be assessed - maximum observed plasma concentration (Cmax), time of maximum observed plasma concentration (Tmax), area under the plasma concentration-time curve (AUC), accumulation, dose proportionality and estimated time to steady-state,
Timepoint [3] 302891 0
PK blood samples taken on:
Days 1 and 28 (pre-study medication application and 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours post drug administration)
Days 2 and 29 (24 hours post drug administration on days 1 and 28 respectively)
Days 7 and 14 (pre-study medication application)
Secondary outcome [1] 337039 0
Not applicable - there are no secondary outcomes
Timepoint [1] 337039 0
Not applicable - there are no secondary outcomes

Eligibility
Key inclusion criteria
- BMI of 18 to 40, inclusive
- Mild to moderate plaque psoriasis less than or equal to 10% body surface area
- A single, non-intertriginous lesion with target plaque area great than or equal to 30 and less than or equal to 60 cm2.
- Target Plaque Severity Score greater than or equal to 5 and less than or equal to 10 with Induration score greater than or equal to 2 and less than or equal to 4.
- Willing to avoid extensive sun exposure, phototherapy, or use of a tanning salon
- Subject must read and understand the informed consent form, and sign it prior to any study-related procedure being performed
- Willingness to comply with all scheduled study visits, laboratory tests, contraception requirements, and other study procedures
- Study cohort is open for randomization
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Women who are pregnant or lactating.
- Women of childbearing potential who are sexually active and are not willing to use birth control
- Males who are sexually active and not willing to use a condom
- History of allergy to investigational product/placebo ingredients
- Recent use of any topical treatment for plaque psoriasis
- Prior treatment with prescription medication for plaque psoriasis with no improvement in condition
- Prior treatment of plaque psoriasis with biologic therapies
- History of or current skin disease
- History of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, musculoskeletal, immunologic, neurologic or dermatologic disease
- History of malignancy within the last 5 years
- Recent treatment with an investigational product
- History of cardiac arrhythmia
- Has current drug-induced psoriasis
- Excessive hair in the treatment area
- Unwilling to refrain from blood, plasma, platelet, or sperm donation
- Clinically significant laboratory abnormalities at Screening
- Clinically significant vital signs at Screening
- Active infection of hepatitis B or C or HIV
- Recent active infection or febrile illness
- Recent serious illness requiring hospitalization
- Positive urine drug screen result at Screening
- Previous treatment with SM04755
- Subjects who have a current or pending disability claim, workers’ compensation, or litigation(s)
- Subjects who are immediate family members of personnel directly affiliated with the study at any investigative site, or are directly affiliated with the study at any investigative site.
- Subjects employed by Samumed, LLC, or any of its affiliates or development partners responsible for the conduct of the study

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)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Other
Other design features
This study is a Multiple Ascending Dose safety study in subjects with mild to moderate Plaque Psoriasis.

Eligible subjects will be randomised to topical SM04755 solution or placebo. The dose of SM04755 will be escalated in successive cohorts of 16 subjects per dose level. If less than 4 subjects in the active group at a dose level experience a dose-limiting toxicity (DLT), then 16 new subjects may be treated at the next higher dose level. New dose-level cohorts may begin accrual only if 14 of 16 subjects at the current dose level have been observed for a minimum of 28 days from the first day of study medication administration and the data from these subjects has been reviewed by the Safety Review Committee (SRC). Safety data for each cohort will be reviewed by the SRC prior to escalation to the next cohort and immediately following any DLT. Upon review and approval of escalation to a subsequent dose level, no further subjects will be enrolled at the current dose level.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size for this study is not based on statistical power calculations, but is consistent with typical sample sizes used for similar studies to assess safety and PK.

In general, for continuous variables, number of subjects in the analysis, mean, standard deviation (SD), median, minimum and maximum will be reported. All categorical endpoints will be summarized using frequencies and percentages. All subjects who receive placebo, regardless of cohort, will be combined into a single treatment group.

Analysis of safety and tolerability primary endpoints will be performed on the Safety Analysis Set.

SM04755 plasma concentration data for the evaluation of systemic exposure will be summarized with descriptive statistics and, when possible (with appropriate plasma concentration-time data), PK parameters will be estimated and summarized with descriptive statistics. Dose proportionality across treatment groups will also be assessed.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The decision to close the study is based on various commercial factors. It does not reflect any safety or efficacy concerns or issues.
Date of first participant enrolment
Anticipated
18/10/2017
Actual
9/10/2017
Date of last participant enrolment
Anticipated
28/02/2019
Actual
3/07/2018
Date of last data collection
Anticipated
30/11/2018
Actual
14/08/2018
Sample size
Target
48
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 8622 0
Veracity Clinical Research - Woolloongabba
Recruitment hospital [2] 11403 0
Sinclair Dermatology - East Melbourne
Recruitment hospital [3] 11404 0
Skin and Cancer Foundation Australia (Westmead) - Westmead
Recruitment postcode(s) [1] 16730 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 23307 0
3002 - East Melbourne
Recruitment postcode(s) [3] 23308 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 296746 0
Commercial sector/Industry
Name [1] 296746 0
Samumed Pacific Pty Ltd
Country [1] 296746 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Samumed Pacific Pty Ltd
Address
Level 15 Exchange Tower
2 The Esplanade
Perth WA 6000
Country
Australia
Secondary sponsor category [1] 295720 0
None
Name [1] 295720 0
Address [1] 295720 0
Country [1] 295720 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297973 0
Bellberry Limited
Ethics committee address [1] 297973 0
Ethics committee country [1] 297973 0
Australia
Date submitted for ethics approval [1] 297973 0
21/06/2017
Approval date [1] 297973 0
15/08/2017
Ethics approval number [1] 297973 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75630 0
Dr Lynda SPELMAN
Address 75630 0
Veracity Clinical Research Pty Ltd
Suite 18, Level 1
250 Ipswich Rd
Woolloongabba QLD 4102
Country 75630 0
Australia
Phone 75630 0
+61 7 3039 1311
Fax 75630 0
+61 7 3391 6239
Email 75630 0
spelchat@iinet.net.au
Contact person for public queries
Name 75631 0
Yusuf YAZICI
Address 75631 0
Samumed, LLC
9381 Judicial Dr, Suite 160
San Diego, CA 92121
Country 75631 0
United States of America
Phone 75631 0
+1 858 926 2926
Fax 75631 0
+1 858 926 9315
Email 75631 0
yusuf@samumed.com
Contact person for scientific queries
Name 75632 0
Yusuf YAZICI
Address 75632 0
Samumed, LLC
9381 Judicial Dr, Suite 160
San Diego, CA 92121
Country 75632 0
United States of America
Phone 75632 0
+1 858 926 2926
Fax 75632 0
+1 858 926 9315
Email 75632 0
yusuf@samumed.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This trial studies a regulated drug product that was not approved, licensed or cleared by any regulator for any use before the Primary Completion Date of the trial, and the sponsor intends to continue with product development and may at a future date seek regulatory approval, licensure, or clearance of the drug product under study


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
SourceTitleYear of PublicationDOI
EmbaseThe european league against rheumatism (EULAR) - 2018 annual european congress of rheumatology: Amsterdam, the Netherlands - June 13-16, 2018.2018https://dx.doi.org/10.1358/dof.2018.043.09.2866116
N.B. These documents automatically identified may not have been verified by the study sponsor.