Clinical Trial Results:
An Open-Label, Long-Term Extension Study to Evaluate the Safety of Cortexolone 17α-Propionate (CB-03-01) Cream, 1% Applied Twice-Daily in Subjects with Acne Vulgaris
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Summary
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EudraCT number |
2015-002637-21 |
Trial protocol |
RO BG PL |
Global end of trial date |
31 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Nov 2020
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First version publication date |
27 Nov 2020
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Other versions |
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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 |
CB-03-01/27
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02682264 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Cassiopea SpA
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Sponsor organisation address |
Via C. Colombo 1 , Lainate ( MI), Italy, 20045
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Public contact |
Cassiopea Research & Development, CASSIOPEA SpA, +39 02868 91 124, R&D@cassiopea.com
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Scientific contact |
Cassiopea Research & Development, CASSIOPEA SpA, +39 02868 91 124, R&D@cassiopea.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 |
28 May 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Aug 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Aug 2018
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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 |
The primary objective of this study is to determine the long-term safety of CB-03-01 cream, 1% applied twice daily for an additional nine months in subjects with acne vulgaris that participated in the Phase 3 pivotal studies for a total treatment of up to 12 months.
This was a multicenter, open label, long-term extension study for CB-03-01 cream, 1% focused on safety in male and female participants, 9 years or older who completed one of the Phase 3 pivotal studies [CB-03-01/25 and CB-03-01/26]. Participants applied the active medication (CB-03-01 cream, 1%) twice daily to the entire face and, if designated by investigator AND desired by the participant, truncal acne for nine additional months of treatment. Thus, overall participants were exposed to CB-03-01 cream, 1% for a total treatment of up to 12 months (0 or 3 months in the Phase 3 pivotal study and an additional nine months in this long-term safety study).
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Protection of trial subjects |
Male and female subjects 9 years of age or older who were enrolled and completed participation in one of the Phase 3 pivotal studies (CB-03-01/25 and CB-03-01/26) were enrolled in this study from study centers in the US, Poland, Bulgaria, Ukraine, Romania, Serbia, and Republic of Georgia. Interested individuals were given an opportunity to discuss the procedures involved in study participation with the site staff and the principal investigator. An IRB/IEC/LEC-approved informed consent/assent form and subject instruction sheet was given to the potential subject and an opportunity afforded to read , discuss and understand the consent/assent form and ask questions.
This study was conducted in accordance with principles of the Declaration of Helsinki (7th revision), with the current Good Clinical Practice guidelines (ICH E6, Revision 2) and with other applicable regulations. The investigators and all study staff conducted the study in compliance with the study protocol.
The rights, safety, and well-being of the study subjects were the most important considerations and prevailed over the interests of science and society.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Mar 2016
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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 |
Poland: 134
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Country: Number of subjects enrolled |
Romania: 73
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Country: Number of subjects enrolled |
Bulgaria: 48
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Country: Number of subjects enrolled |
United States: 242
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Country: Number of subjects enrolled |
Ukraine: 56
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Country: Number of subjects enrolled |
Georgia: 30
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Country: Number of subjects enrolled |
Serbia: 26
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Worldwide total number of subjects |
609
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EEA total number of subjects |
255
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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) |
9
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Adolescents (12-17 years) |
304
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Adults (18-64 years) |
296
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
There were 609 subjects who were rolled over (i.e., enrolled) from the two Phase 3 pivotal studies (CB-03-01/25 and CB-03-01/26) into this long-term, safety study. However, two (2) subjects in the original vehicle cream were not treated with test article and thus were excluded from the study population (Safety set). | ||||||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
not applicable | ||||||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Follow -up (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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CB-03-01 1% cream | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects in this arm received CB-03-01 (cortexolone 17α-propionate) Cream, 1% in the pivotal study and continued their CB-03-01 cream treatment in this open-label safety extension study. Subjects were instructed to apply CB-03-01 Cream, 1%, twice daily to whole face (about 1 gram) and affected areas of trunk (if applicable) for up to an additional 9 months. Over the course of the study, treatment on the face and/or trunk may be discontinued if/when acne clears and re-started if/when acne worsens, according to the assessment of the investigator for each respective treatment area. Cortexolone 17α-propionate (USAN/INN: clascoterone) is an androgen receptor inhibitor that is being developed as a 1% cream for the topical treatment of acne vulgaris. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
CB-03-01 | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Clascoterone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream
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Routes of administration |
Topical use
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Dosage and administration details |
Participants applies the active medication (CB-03-01 cream, 1%) twice daily to the entire face and, if designated by investigator AND desired by the participant, truncal acne for nine additional months of treatment. Thus, overall participants were exposed to CB-03-01 cream, 1% for a total treatment of up to 12 months (0 or 3 months in the Phase 3 pivotal study and an additional nine months in this long-term safety study).
Participants treated facial acne per protocol for nine months. Treatment of truncal acne was discussed by the investigator and participant. Treatment on the face and/or trunk was discontinued if/when acne clears and re-started if/when acne worsens, according to the assessment of the investigator for each respective treatment area.
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Arm title
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CB-03-01 Cream, 1% (Vehicle Arm) | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects in this arm received vehicle cream in the pivotal study and CB-03-01 cream in this open-label safety extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
CB-03-01 (vehicle) | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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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: there were 609 subjects who were rolled over (i.e., enrolled) from the two Phase 3 pivotal studies (CB-03-01/25 and CB-03-01/26) into this long-term, safety study. However, two (2) subjects in the original vehicle cream were not treated with test article and thus were excluded from the study population (Safety set). |
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Baseline characteristics reporting groups
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Reporting group title |
CB-03-01 1% cream
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Reporting group description |
Subjects in this arm received CB-03-01 (cortexolone 17α-propionate) Cream, 1% in the pivotal study and continued their CB-03-01 cream treatment in this open-label safety extension study. Subjects were instructed to apply CB-03-01 Cream, 1%, twice daily to whole face (about 1 gram) and affected areas of trunk (if applicable) for up to an additional 9 months. Over the course of the study, treatment on the face and/or trunk may be discontinued if/when acne clears and re-started if/when acne worsens, according to the assessment of the investigator for each respective treatment area. Cortexolone 17α-propionate (USAN/INN: clascoterone) is an androgen receptor inhibitor that is being developed as a 1% cream for the topical treatment of acne vulgaris. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CB-03-01 Cream, 1% (Vehicle Arm)
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Reporting group description |
Subjects in this arm received vehicle cream in the pivotal study and CB-03-01 cream in this open-label safety extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety Analysis
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Safety population defined as all subjects who applied at least one dose of test article.
There were 609 subjects who were rolled over (i.e., enrolled) from the two Phase 3 pivotal studies (CB-03-01/25 and CB-03-01/26) into this long-term, safety study. However, two (2) subjects in the original vehicle cream were not treated with test article and thus were excluded from the study population (Safety set).
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End points reporting groups
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Reporting group title |
CB-03-01 1% cream
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Reporting group description |
Subjects in this arm received CB-03-01 (cortexolone 17α-propionate) Cream, 1% in the pivotal study and continued their CB-03-01 cream treatment in this open-label safety extension study. Subjects were instructed to apply CB-03-01 Cream, 1%, twice daily to whole face (about 1 gram) and affected areas of trunk (if applicable) for up to an additional 9 months. Over the course of the study, treatment on the face and/or trunk may be discontinued if/when acne clears and re-started if/when acne worsens, according to the assessment of the investigator for each respective treatment area. Cortexolone 17α-propionate (USAN/INN: clascoterone) is an androgen receptor inhibitor that is being developed as a 1% cream for the topical treatment of acne vulgaris. | ||
Reporting group title |
CB-03-01 Cream, 1% (Vehicle Arm)
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Reporting group description |
Subjects in this arm received vehicle cream in the pivotal study and CB-03-01 cream in this open-label safety extension study. | ||
Subject analysis set title |
Safety Analysis
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety population defined as all subjects who applied at least one dose of test article.
There were 609 subjects who were rolled over (i.e., enrolled) from the two Phase 3 pivotal studies (CB-03-01/25 and CB-03-01/26) into this long-term, safety study. However, two (2) subjects in the original vehicle cream were not treated with test article and thus were excluded from the study population (Safety set).
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End point title |
Incidence of Any Local and Systemic Treatment Emergent AEs (TEAEs) [1] | ||||||||||||
End point description |
Number of subjects with any local and systemic treatment emergent AEs (TEAEs)
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End point type |
Primary
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End point timeframe |
up to 52 weeks
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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: Descriptive statistics . All AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 and listed. Individual TEAEs (i.e., all the AEs occurring or worsening after the first dose of the test article) were listed, documenting course, severity, relationship to test article, and outcome. The number and percentage of subjects with any TEAE and the number of TEAEs were presented overall and were tabulated by MedDRA system organ class (SOC) and by preferred term (PT). |
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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 |
Treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) were collected from Baseline (Long-term study Day 1) and up to Long-term study month 9/early termination.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
CB-03-01 Cream, 1%
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Reporting group description |
Subjects in this arm received CB-03-01 (cortexolone 17α-propionate) Cream, 1% in the pivotal study and continued their CB-03-01 cream treatment in this open-label safety extension study. Subjects were instructed to apply CB-03-01 Cream, 1%, twice daily to whole face (about 1 gram) and affected areas of trunk (if applicable) for up to an additional 9 months. Over the course of the study, treatment on the face and/or trunk may be discontinued if/when acne clears and re-started if/when acne worsens, according to the assessment of the investigator for each respective treatment area. Cortexolone 17α-propionate (USAN/INN: clascoterone) is an androgen receptor inhibitor that is being developed as a 1% cream for the topical treatment of acne vulgaris. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CB-03-01 Cream, 1% (Vehicle Arm)
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Reporting group description |
Subjects in this arm received vehicle cream in the pivotal study and CB-03-01 cream in this open-label safety extension study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0.7% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | |||
