Clinical Trial Results:
Safety and efficacy of repeat use of Picato® 0.05% in the treatment of anogenital warts
Summary
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EudraCT number |
2014-004465-24 |
Trial protocol |
DK |
Global end of trial date |
26 Nov 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Dec 2016
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First version publication date |
08 Dec 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EXP-1167
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02377999 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
LEO Pharma A/S
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Sponsor organisation address |
Industriparken 55, Ballerup, Denmark, 2750
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Public contact |
Clinical Trial Disclosure Manager, LEO Pharma A/S, 45 44945888, ctr.disclosure@leo-pharma.com
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Scientific contact |
Clinical Trial Disclosure Manager, LEO Pharma A/S, 45 44945888, ctr.disclosure@leo-pharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Jun 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Nov 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Nov 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety of single treatment with Picato® 0.05% repeated up to 2 times with two weeks intervals in subjects with anogenital warts.
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Protection of trial subjects |
NA
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Mar 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 41
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Worldwide total number of subjects |
41
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EEA total number of subjects |
41
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
39
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 41 subjects were enrolled in the trial, 1 subject was a screening failure, and 40 subjects were assigned treatment with ingenol mebutate gel 0.05%. All subjects were enrolled at a single site in Denmark. | ||||||||||||||||
Pre-assignment
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Screening details |
A screening visit was conducted up to 7 days before start of treatment to screen for eligibility, to obtain informed consent, and collect demographic and baseline data. | ||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Arm title
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All subjects | ||||||||||||||||
Arm description |
Of the 40 subjects assigned treatment, 22 subjects (55%) received 1 dose of ingenol mebutate gel 0.05%, 8 subjects (20%) received 2 doses and 10 subjects (25%) received 3 doses. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
ingenol mebutate gel 0.05%
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Investigational medicinal product code |
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Other name |
Picato® gel 0.05%
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Pharmaceutical forms |
Gel
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Routes of administration |
Topical use
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Dosage and administration details |
Ingenol mebutate gel 0.05% was applied to the genital wart on Day 1 and if complete clearance of the genital wart was not obtained on Day 15, ingenol mebutate gel 0.05% was to be applied again on Day 15 and Day 29, as applicable.
The applications were done at the trial site by the (sub)investigator.
Any hair on the treatment area was cut with scissors to a length of maximum 2-3 mm. Picato® gel was applied in a generous amount, covering the genital wart in a thick layer and also covering 1-2 mm of the normal skin surrounding the wart.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 1 enrolled subject was a screening failure and was not assigned to treatment. |
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Baseline characteristics reporting groups
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Reporting group title |
All subjects
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Reporting group description |
Of the 40 subjects assigned treatment, 22 subjects (55%) received 1 dose of ingenol mebutate gel 0.05%, 8 subjects (20%) received 2 doses and 10 subjects (25%) received 3 doses. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All subjects
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Reporting group description |
Of the 40 subjects assigned treatment, 22 subjects (55%) received 1 dose of ingenol mebutate gel 0.05%, 8 subjects (20%) received 2 doses and 10 subjects (25%) received 3 doses. | ||
Subject analysis set title |
Subjects receiving 1 dose
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received 1 dose of IMP.
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Subject analysis set title |
Subjects receiving 2 doses
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received 2 doses of IMP.
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Subject analysis set title |
Subjects receiving 3 doses
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received 3 doses of IMP.
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Subject analysis set title |
Day 15
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who were assessed on Day 15/Visit 4.
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Subject analysis set title |
Day 29
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who were assessed on Day 29/Visit 5.
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Subject analysis set title |
Day 43
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who were assessed on Day 43/Visit 6.
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Subject analysis set title |
Follow-up
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who were assessed at follow-up visit - 12 weeks after Day 29 or Day 43.
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End point title |
Safety and tolerability - Day of Maximum Composite Local Skin Reaction (LSR) score by number of doses [1] | ||||||||||||||||||||
End point description |
The primary endpoint of this trial was incidence and severity of LSRs and treatment related AEs, assessed by:
-Day of Maximum Composite LSR score by number of doses
-Maximum Composite LSR score across visits
-Maximum Composite LSR score across visits by treated area
LSRs were assessed for presence/absence and grade (0 to 3) of the following individual LSRs: erythema, edema, weeping/exudate, vesiculation/blistering, crusting/(scabbing), and erosion/ulceration. A composite LSR score (0 to 18), reflecting the sum of the individual LSR components, was calculated at each visit.
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End point type |
Primary
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End point timeframe |
Day 1 to Day 43
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As this was an exploratory trial, no statistical analysis was planned. |
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No statistical analyses for this end point |
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End point title |
Safety and tolerability - Maximum Composite Local Skin Reaction (LSR) score across visits by number of doses [2] | |||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 1 to Day 43
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As this was an exploratory trial, no statistical analysis was planned. |
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No statistical analyses for this end point |
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End point title |
Safety and tolerability - Maximum Composite Local Skin Reaction (LSR) score across visits by treated area [3] | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 1 to Day 43
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As this was an exploratory trial, no statistical analysis was planned. |
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Notes [4] - 40 subjects with a total of 53 (n=53) treated areas |
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No statistical analyses for this end point |
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End point title |
Complete Clearance of Anogenital Warts 14 Days after Last Treatment Application | ||||||||||||||||||||||||||||||
End point description |
Complete clearance of anogenital warts after end of trial (defined as 14 days after last treatment application) and by visits.
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End point type |
Secondary
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End point timeframe |
14 Days after last treatment application
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Notes [5] - Assessment was missing for 1 subject withdrawn at visit 3 |
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No statistical analyses for this end point |
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End point title |
Percentage Reduction in Anogenital Wart Count from Baseline to End of Trial | ||||||||||||||||||||||||||||||
End point description |
Percentage reduction in anogenital wart count from baseline to end of trial (defined as 14 days after last treatment application) and by visit.
‘End of trial’ measure was defined as occurring 14 days after last treatment application.
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End point type |
Secondary
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End point timeframe |
Day 1 to End of Trial
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No statistical analyses for this end point |
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End point title |
Recurrence Rate - subject level | ||||||||||
End point description |
Recurrence of genital warts was assessed 12 weeks after Day 29 or Day 43 for subjects with complete clearance at any previous visit.
Reporting group: 16 subjects had complete clearance at the last visit, but 2 subjects did not attend the follow-up visit and were not assessed for recurrence. 8 out of 14 subjects (57.1%) had recurrence.
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End point type |
Secondary
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End point timeframe |
12 weeks after Day 29 or Day 43
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Notes [6] - 16 subjects subjects had complete clearance at the last visit. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Day 1 to the end of follow-up after final treatment (12 weeks from Day 29 or Day 43)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.1
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Reporting groups
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Reporting group title |
All subjects
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |