An Evaluation of the Adrenal Suppression Potential and PK of CB-03-01 Cream in Pediatric Patients With Acne Vulgaris

• Sponsor: Cassiopea SpA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02720627
• Collaborator: (none)
• Enrollment: 27
• Locations: 10
• Arm: 1
• Actual Duration (Months): 16.7
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is designed to determine the hypothalamic-pituitary-adrenal (HPA) axis suppression potential and pharmacokinetic (PK) properties of CB-03-01 Cream, 1%, applied every twelve hours for two weeks, in pediatric patients 9 to less than 12 years of age with acne vulgaris. Adrenal suppression effects and systemic safety are an important safety concern. The current study is designed to investigate these potential concerns under maximal use conditions.

Condition or Disease	Intervention/Treatment	Phase
Acne Vulgaris	Drug: cortexolone 17α-propionate	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Evaluation of the Adrenal Suppression Potential and Trough Plasma Concentrations of Cortexolone 17α-Propionate (CB-03-01) Cream Applied Every 12 Hours for Two Weeks in Subjects 9 to <12 Years of Age With Acne Vulgaris
• Actual Study Start Date: Oct 28, 2016
• Actual Primary Completion Date: Mar 21, 2018
• Actual Study Completion Date: Mar 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CB-03-01 cream, 1% Topical CB-03-01 (cortexolone 17α-propionate) cream containing 1% active drug applied to the face and trunk twice daily for 14 days	Drug: cortexolone 17α-propionate; CB-03-01 cream is a topical steroidal antiandrogen that is being developed for the potential treatment of acne vulgaris, an androgen-dependent skin disorder.; Other Names: CB-03-01

Outcome Measures

Primary Outcome Measures

1. Change in HPA Axis Response as Measured by CST [Pre- and Post-CST on Day 14]

   Measurement of serum cortisol concentrations after stimulation of the adrenal cortex with cosyntropin (Cosyntropin Stimulation Test - CST). HPA axis suppression is defined as a post-stimulation serum cortisol level ≤ 18 μg/dL at Day 14.

Secondary Outcome Measures

1. Evaluate Trough Plasma Concentrations [14 Days]

   Trough (single blood draw approximately 12 hours post the most recent dose) measurements of cortexolone 17α-propionate (clascoterone) concentration in plasma at Screening, Baseline, Day 7 and Day 14.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient must provide written informed assent and be accompanied by the parent or legal guardian at the time of assent/consent signing. The parent or legal guardian must provide written informed consent for the patient.

• Patient has moderate to severe facial acne vulgaris as determined by the Investigator and obvious acne on the trunk (i.e., shoulders, upper chest, and/or back).

• Females of childbearing potential must be using highly effective birth control methods with a negative urine pregnancy test (UPT) at study start.

• Patient must be in general good health with normal renal function and no clinically relevant abnormalities present at study start.

• Patient and parent/guardian are able to communicate with the staff and are willing to comply with study instructions, reside at and/or return to the clinic for required visits.

Exclusion Criteria:

• Patient is pregnant, lactating, or is planning to become pregnant during the study.

• Patient has a Body Mass Index (BMI) for age percentile > 95%.

• Patient has any skin or medical condition, including facial hair that could interfere with the evaluation of the test article or requires the use of interfering topical or systemic therapy.

• Patient has received an investigational drug or been treated with an investigational device within 30 days prior to study start.

• Patient is currently enrolled in an investigational drug or device study.

• Patient has any condition which, in the investigator's opinion, would make it unsafe for the patient to participate in this research study.

• Patient has known allergy or sensitivity to CB-03-01 or any of its ingredients

• Patient has participated in a previous CB-03-01 study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 103	Fort Smith	Arkansas	United States	72916
2	Site 101	San Diego	California	United States	92037
3	Site 102	Houston	Texas	United States	77030
4	Site 4814	Czestochowa		Poland
5	Site 4811	Katowice		Poland
6	Site 4813	Kraków		Poland
7	Site 4815	Kraków		Poland
8	Site 4816	Rzeszów		Poland
9	Site 4812	Szczecin		Poland
10	Site 4817	Tarnów		Poland

Sponsors and Collaborators

• Cassiopea SpA

Investigators

• Study Director: R&D Department, Cassiopea SpA

Study Documents (Full-Text)

• Study Protocol - Feb 18, 2016
• Statistical Analysis Plan - Nov 17, 2017

More Information

Publications

None provided.

• Responsible Party: Cassiopea SpA
• ClinicalTrials.gov Identifier: NCT02720627
• Other Study ID Numbers: CB-03-01/28
• First Posted: Mar 28, 2016
• Last Update Posted: Nov 20, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Cassiopea SpA: acne; cortexolone; anti-androgen
• Additional relevant MeSH terms: Acne Vulgaris

Study Results

Participant Flow

Arm/Group Title	CB-03-01 Cream, 1%
Arm/Group Description	Topical CB-03-01 (cortexolone 17α-propionate) cream containing 1% active drug applied to the face and trunk twice daily for 14 days cortexolone 17α-propionate (USAN/INN: clascoterone): is a topical steroidal antiandrogen that is being developed for the potential treatment of acne vulgaris, an androgen-dependent skin disorder.
Period Title: Overall Study
STARTED	27
COMPLETED	27
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	CB-03-01 Cream, 1%
Arm/Group Description	Topical CB-03-01 (cortexolone 17α-propionate) cream containing 1% active drug applied to the face and trunk twice daily for 14 days cortexolone 17α-propionate (USAN/INN: clascoterone): is a topical steroidal antiandrogen that is being developed for the potential treatment of acne vulgaris, an androgen-dependent skin disorder.
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.2 (0.9)
Sex: Female, Male (Count of Participants)
Female	22 81.5%
Male	5 18.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 25.9%
Not Hispanic or Latino	20 74.1%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.7%
White	25 92.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Baseline HPA Axis Response (mcg/dL) [Mean (Standard Deviation) ]
Cortisol Level (Pre-CST)	13.53 (4.53)
Cortisol Level (Post-CST)	24.87 (3.70)

Outcome Measures

1. Primary Outcome

Title	Change in HPA Axis Response as Measured by CST
Description	Measurement of serum cortisol concentrations after stimulation of the adrenal cortex with cosyntropin (Cosyntropin Stimulation Test - CST). HPA axis suppression is defined as a post-stimulation serum cortisol level ≤ 18 μg/dL at Day 14.
Time Frame	Pre- and Post-CST on Day 14

Outcome Measure Data

Analysis Population Description

Evaluable population, defined as all subjects in the safety population who had evaluable cortisol assay data.

Arm/Group Title	CB-03-01 Cream, 1%
Arm/Group Description	Topical CB-03-01 (cortexolone 17α-propionate) cream containing 1% active drug applied to the face and trunk twice daily for 14 days cortexolone 17α-propionate (USAN/INN: clascoterone): is a topical steroidal antiandrogen that is being developed for the potential treatment of acne vulgaris, an androgen-dependent skin disorder.
Measure Participants	23
Cortisol level (Pre-CST)	12.50 (4.90)
Cortisol level (Post-CST)	22.95 (3.20)

2. Secondary Outcome

Title	Evaluate Trough Plasma Concentrations
Description	Trough (single blood draw approximately 12 hours post the most recent dose) measurements of cortexolone 17α-propionate (clascoterone) concentration in plasma at Screening, Baseline, Day 7 and Day 14.
Time Frame	14 Days

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) population included those subjects in the Safety population who had at least an 80% dose compliance based on number of applications, had at least one post-baseline PK blood draw within ±2 days of the scheduled visit at Days 7 and 14, and did not have any significant protocol deviations.

Arm/Group Title	CB-03-01 Cream, 1%
Arm/Group Description	Topical CB-03-01 (cortexolone 17α-propionate) cream containing 1% active drug applied to the face and trunk twice daily for 14 days cortexolone 17α-propionate (USAN/INN: clascoterone): is a topical steroidal antiandrogen that is being developed for the potential treatment of acne vulgaris, an androgen-dependent skin disorder.
Measure Participants	25
Screening	0.0 (0.0)
Baseline (Day 1)	0.027 (0.136)
Day 7	0.577 (1.01)
Day 14	0.606 (0.701)

Adverse Events

Time Frame	14 Days or up to 42 days for those with laboratory evidence of adrenal suppression (i.e., post-stimulation serum cortisol level ≤18 μg/dL at Day 14).
Adverse Event Reporting Description	Any treatment emergent AEs ongoing at the end of the treatment period (Day 14) were followed until they resolve, the condition stabilizes, the events are otherwise explained, or the subject is lost to follow-up. In addition, all SAEs were followed until resolution as previously stated for study product-related AEs. Subjects with laboratory evidence of adrenal suppression at Day 14 were required to be re-tested 4 weeks later (Day 42); all four subjects returned to normal HPA function.
Arm/Group Title	CB-03-01 Cream, 1%
Arm/Group Description	Topical CB-03-01 (cortexolone 17α-propionate) cream containing 1% active drug applied to the face and trunk twice daily for 14 days cortexolone 17α-propionate (USAN/INN: clasocoterone): is a topical steroidal antiandrogen that is being developed for the potential treatment of acne vulgaris, an androgen-dependent skin disorder.
All Cause Mortality
	CB-03-01 Cream, 1%
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Serious Adverse Events
	CB-03-01 Cream, 1%
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Other (Not Including Serious) Adverse Events
	CB-03-01 Cream, 1%
	Affected / at Risk (%)	# Events
Total	5/27 (18.5%)
Blood and lymphatic system disorders
Leukopenia	1/27 (3.7%)	1
Investigations
ACTH stimulation test abnormal	4/27 (14.8%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor has first right to publish pooled study data. In the event that such manuscript has not been submitted for publication within 18 months from study completion/termination at all participating sites, the PI shall have the right to single center publications provided they submit any data for presentation, oral or written, to the Sponsor for review 60 days prior to public disclosure. The PI may not disclose previously undisclosed confidential information other than study results.