Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000711314
Ethics application status
Approved
Date submitted
2/05/2017
Date registered
17/05/2017
Date last updated
21/12/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Clinical trial investigating if anti-malaria treatment DSM265 causes an allergic reaction.
Scientific title
Allergic potential of DSM265 in human subjects: a Skin Prick Test Study .
Secondary ID [1] 291782 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tolerability of Anti-Malaria Vaccine 303012 0
Condition category
Condition code
Inflammatory and Immune System 302469 302469 0 0
Allergies
Infection 302633 302633 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single study split into 3 parts. Data from part 1 will be used to determine dilution concentrations of DSM265 for Part 2 and safety data from Part 2 will determine proceeding to Part 3. Healthy volunteers involved in Part 1 only . A single participant who was previously experienced a experienced a cutaneous allergic reaction to DSM265 will participate in Parts 2 and 3.
Part 1:
Skin Prick Test with:
-4 incremental concentrations (1:1000, 1:100, 1: 10 and 1:1) of DSM265 solutions
- Positive control (histamine dihydrochloride)
-Negative control (glycerine-saline).
All participants will receive all four doses of DSM265.
Safety Assessments (clinical haematology and biochemistry blood tests, viral serology (HIV, Hep B, Hep C) vitals signs, ECG, urinalysis)
Urine Drug screening
Pregnancy Testing

Part 2:
Skin Prick Test:
-3 incremental concentrations of the non-irritant dose of DSM265 determined from Part 1 (1:1, 1:10, 1:100)
-Positive control (histamine dihydrochloride)
-Negative control (glycerine-saline)
-Reference concentration (1:1000) of Polysorbate 80
Safety Assessments (clinical haematology and biochemistry blood tests, viral serology (HIV, Hep B, Hep C) vitals signs, ECG, urinalysis)
Urine Drug screening
Pregnancy Testing

Part 3:
Oral dose of DSM265 of up to 400mg . The patient will be given an initial dose equivalent to 1:10 (40mg) of the previous dose linked to the cutaneous reaction in study QP15C11.
If there has been no development of signs or symptoms of a reaction after 2 hours of the first dose, a second dose equivalent to 9:10 (360mg) of DSM 265 will be given and the patient observed for a further 3 hours.
Safety Assessments (clinical haematology and biochemistry blood tests, viral serology (HIV, Hep B, Hep C) vitals signs, ECG, urinalysis)
Urine Drug screening
Pregnancy Testing
skin biopsy (if required)
Intervention code [1] 297892 0
Early detection / Screening
Intervention code [2] 298015 0
Prevention
Comparator / control treatment
Positive and Negative controls are used for Skin Prick Tests in parts 1 and 2.
Positive control (histamine dihydrochloride)
Negative control (glycerine-saline)
Control group
Active

Outcomes
Primary outcome [1] 301891 0
Part 1 (healthy volunteers): Local safety and tolerability of DSM265 during SPT procedure. The largest diameter of the wheal of each individual test is measured, a positive reading being a wheal of greater than or equal to 3mm with or without erythema. In case of a positive reaction with the negative control, the SPT must be regarded as non-reliable.
Similarly, the skin tests results to the two possible allergens (DSM265 and Polysorbate 80) will be interpreted independently of the size of the histamine reaction. Photographs of the skin may be taken to assist with interpretation of the reaction and kept as part of the study records.
Subjects will be monitored and safety data collected by way of clinical interviews, observations and examinations, through ECG reports and laboratory evaluations.
Timepoint [1] 301891 0
Part 1 Skin Prick Test results will be assessed for each participant 6 hours post skin prick test.
Safety Review Meeting will be conducted within 7 days of SPT procedure to review the data and confirm safe to proceed to Part 2 and non-irritant dose of DSM265.
Primary outcome [2] 302044 0
Part 2 (single subject): SPT results (DSM265, polysorbate 80, histamine, glycerine-saline), The largest diameter of the wheal of each individual test is measured, a positive reading being a wheal of greater than or equal to 3mm with or without erythema. In case of a positive reaction with the negative control, the SPT must be regarded as non-reliable.
Similarly, the skin tests results to the two possible allergens (DSM265 and Polysorbate 80) will be interpreted independently of the size of the histamine reaction. Photographs of the skin may be taken to assist with interpretation of the reaction and kept as part of the study records.
Subjects will be monitored and safety data collected by way of clinical interviews, observations and examinations, through ECG reports and laboratory evaluations.
Timepoint [2] 302044 0
Part 2 Skin Prick Test results will be assessed for single participant 8 hours post skin prick test.
Safety Review Meeting conducted within 7 days of SPT procedure will be conducted to review the data and confirm safe to proceed to Part 3.
Primary outcome [3] 302045 0
Part 3 (subject R107 only): Safety/tolerability & clinical allergic manifestations following oral dose of DSM265,
The patient will be observed and monitored for changes in vital signs or development of cutaneous or systemic symptoms. These will be recorded every 15minutes for the first hour after dosing and every 30 minutes there after till 8 hours post dose.
Timepoint [3] 302045 0
Safety outcomes will be assessed every 15 minutes for the first hour and every 30 minutes there after till 8 hours post dose of DSM265.
Secondary outcome [1] 334196 0
Part 3: Histology of cutaneous lesions (if a biopsy is performed).
Timepoint [1] 334196 0
Skin biopsy collected if cutaneous rash occurs following oral administration of DSM265 in Part 3 of the study. Biopsy collected up to 72hours post DSM265 administration.
Secondary outcome [2] 334834 0
Part 2 (single subject): HLA alleles determination.
Timepoint [2] 334834 0
HLA determination will be available from laboratory within 24 hours of blood collection.

Eligibility
Key inclusion criteria
Single study split into 3 parts. Healthy Volunteers for Part 1 and known participant R107 (from previous study) for part 2 and 3
PART 1
Healthy male or female 18-55 y.o
No clinically significant abnormality on vital signs, safety laboratory tests and ECGs within normal range at screening.
PART 2 - known participant to be screened to ensure participant safety:
No clinically significant abnormality on vital signs, safety laboratory tests and ECGs within normal range at screening.
PART 3 - known participant to be screened to ensure participant safety:
No clinically significant abnormality on vital signs, safety laboratory tests and ECGs within normal range at screening and admission.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
PART 1
Diffuse dermatological conditions (requirement for healthy skin for testing)
Severe dermatographism
Severe or uncontrolled asthma
Infections of the skin at the test area
Personal history of allergy (including seasonal allergies/allergic rhinitis)
Acute inflammatory status (i.e. fever 38.0 degrees C and/or CRP 20 mg/L) or with concurrent illness (i.e. viral, bacterial)
Breast-feeding mothers and pregnant females (positive pregnancy test)
Treatments that may interfere with the interpretation of the SPT (listed in appendix of protocol, as well as the following class of drugs : beta-blockers, ACE (Angiotensin-converting-enzyme) inhibitors, calcineurin inhibitors, systemic corticosteroids, or topical corticosteroids used at the tested skin area. The minimum washout period for these drugs should be 2 weeks or 5 half-lives whichever is the longer.

PART 2
Diffuse dermatological conditions (requirement for healthy skin for testing)
Severe dermatographism
Severe or uncontrolled asthma
Infections of the skin at the test area
Acute inflammatory status (i.e. fever 38.0 degrees C and/or CRP 20 mg/L) or with concurrent illness (i.e. viral, bacterial)
Breast-feeding or positive pregnancy test
Treatments that may interfere with the interpretation of the SPT as well as the following class of drugs : beta-blockers, ACE (Angiotensin-converting-enzyme) inhibitors, calcineurin inhibitors, systemic corticosteroids, or topical corticosteroids used at the tested skin area. The minimum washout period for these drugs should be 2 weeks or 5 half-lives whichever is the longer.

PART 3
Severe or uncontrolled asthma
Acute inflammatory status (i.e. fever 38.0 degrees C and/or CRP 20 mg/L at screening) or with concurrent illness (i.e. viral, bacterial)
Breast-feeding or positive pregnancy test
Treatments that may interfere with the interpretation of the Drug Provocation Test as well as the following class of drugs : beta-blockers, ACE (Angiotensin-converting-enzyme) inhibitors, calcineurin inhibitors, systemic corticosteroids, or topical corticosteroids. The minimum washout period for these drugs should be 2 weeks or 5 half-lives whichever is the longer.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not Applicable - open label
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Part 1: 10 healthy volunteers 18-55 year olds.
Parts 2 & 3: Participant from previous Study QP15C11 who experienced a cutaneous immune response following administration of DSM265.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
All subjects enrolled and tested with at least one Skin Prick Test (Part 1 and 2) and who received an oral dose of DSM265 (Part 3 only) will be included in the data analysis. The subject disposition will be listed and summarised by study part absolute values and change from baseline will be presented when relevant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/05/2017
Actual
16/05/2017
Date of last participant enrolment
Anticipated
29/05/2017
Actual
29/05/2017
Date of last data collection
Anticipated
7/07/2017
Actual
23/06/2017
Sample size
Target
11
Accrual to date
Final
11
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 15848 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 296285 0
Charities/Societies/Foundations
Name [1] 296285 0
Medicines for Malaria Venture (MMV) - Non Profit Product Development Partnership
Country [1] 296285 0
Switzerland
Primary sponsor type
Charities/Societies/Foundations
Name
Medicines for Malaria Venture (MMV) - Non Profit Product Development Partnership
Address
ICC – Block G, 3rd floor
20, route de Pre-Bois
PO Box 1826
1215 Geneva 15
Switzerland
Country
Switzerland
Secondary sponsor category [1] 295207 0
None
Name [1] 295207 0
Address [1] 295207 0
Country [1] 295207 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297518 0
The QIMR Berghofer Medical Research Institute Human Research Ethics Committee (QIMR Berghofer-HREC)
Ethics committee address [1] 297518 0
Ethics committee country [1] 297518 0
Australia
Date submitted for ethics approval [1] 297518 0
21/03/2017
Approval date [1] 297518 0
21/04/2017
Ethics approval number [1] 297518 0
P2308

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

Contacts
Principal investigator
Name 74298 0
Dr Paul Griffin
Address 74298 0
Level 5, QIMR Berghofer CBCRC
300C Herston Road
and
Level 6, Block 8
Royal Brisbane and Women’s Hospital
Herston, QLD 4006
Australia
Country 74298 0
Australia
Phone 74298 0
+61 7 3845 3636
Fax 74298 0
Email 74298 0
[email protected]
Contact person for public queries
Name 74299 0
Paul Griffin
Address 74299 0
Level 5, QIMR Berghofer CBCRC
300C Herston Road
and
Level 6, Block 8
Royal Brisbane and Women’s Hospital
Herston, QLD 4006
Australia
Country 74299 0
Australia
Phone 74299 0
+61 7 3845 3636
Fax 74299 0
Email 74299 0
[email protected]
Contact person for scientific queries
Name 74300 0
Paul Griffin
Address 74300 0
Level 5, QIMR Berghofer CBCRC
300C Herston Road
and
Level 6, Block 8
Royal Brisbane and Women’s Hospital
Herston, QLD 4006
Australia
Country 74300 0
Australia
Phone 74300 0
+61 7 3845 3636
Fax 74300 0
Email 74300 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

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Documents added automatically
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