A Study to Evaluate the Safety and Efficacy of CB-03-01 Cream, 1% in Subjects With Facial Acne Vulgaris (26)

• Sponsor: Cassiopea SpA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02608476
• Collaborator: (none)
• Enrollment: 732
• Locations: 52
• Arms: 2
• Actual Duration (Months): 27.2
• Patients Per Site: 14.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine the safety and efficacy of CB-03-01 cream, 1%, versus the vehicle cream applied twice daily for 12 weeks in subjects with facial acne vulgaris.

Condition or Disease	Intervention/Treatment	Phase
Acne Vulgaris	Drug: CB-03-01 cream, 1%; Drug: Vehicle cream	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 732 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of Cortexolone 17α-Propionate (CB-03-01) Cream, 1% Applied Twice Daily for 12 Weeks in Subjects With Facial Acne Vulgaris
• Actual Study Start Date: Nov 16, 2015
• Actual Primary Completion Date: Feb 21, 2018
• Actual Study Completion Date: Feb 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CB-03-01 cream CB-03-01 cream, 1% applied twice daily for 12 weeks	Drug: CB-03-01 cream, 1%; CB-03-01 (cortexolone 17α-propionate) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.; Other Names: cortexolone 17α-propionate clascoterone (USAN, INN)
Placebo Comparator: Vehicle cream Vehicle cream applied twice daily for 12 weeks	Drug: Vehicle cream; Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Success in Investigator's Global Assessment (IGA) [Week 12]

   Percentage of subjects in each treatment group achieving "success" at Week 12, with "success" defined as an IGA score of "clear (score=0)" or "almost clear (score=1)" and at least a two-point reduction in IGA compared to Baseline.

2. Change From Baseline in Non-inflammatory Lesion (NIL) Counts [Baseline and Week 12]

   Absolute change from Baseline in non-inflammatory lesion counts in each treatment group at Week 12.

3. Change From Baseline in Inflammatory Lesion (IL) Counts [Baseline and Week 12]

   Absolute change from Baseline in inflammatory lesion counts in each treatment group at Week 12.

Secondary Outcome Measures

1. Change From Baseline in Total Lesion Counts [Baseline and Week 12]

   Absolute change from Baseline in total lesions counts in each treatment group at Week 12.

2. Percent Change From Baseline in Total Lesion Counts [Baseline and Week 12]

   Percent change from Baseline in total lesions counts in each treatment group at Week 12.

3. Percent Change From Baseline in Non-inflammatory Lesion Counts [Baseline and Week 12]

   Percent change from Baseline in non-inflammatory lesions count in each treatment group at Week 12.

4. Percent Change From Baseline in Inflammatory Lesion Counts [Baseline and Week 12]

   Percent change from Baseline in inflammatory lesions count in each treatment group at Week 12.

Other Outcome Measures

1. Local Site Reactions [Baseline, Weeks 4, 8, and 12]

   Local Site Reactions (LSRs) including telangiectasia, skin atrophy, striae rubrae, erythema, edema, scaling/dryness, stinging/burning, and pruritus scored by frequency and severity at every visit (Baseline, Weeks 4, 8, and 12).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject is male or non-pregnant female, 9 years of age or older. Females must be post-menopausal, surgically sterile, or using highly effective birth control methods. Women of child-bearing potential must have a negative urine pregnancy test (UPT) at the Screening/Baseline Visit.

2. Subject has provided written and verbal informed consent/assent. A subject under 18 years of age must provide written informed assent and be accompanied by the parent or legal guardian at the time of assent/consent signing.

3. Subject has an Investigator's Global Assessment (IGA) score of 3 (moderate) or 4 (severe) [0 (clear) to 4 (severe) scale].

4. Subject has facial acne vulgaris with at least 30 to a maximum of 75 inflammatory lesions (papules, pustules, and nodules) and 30 to a maximum of 100 non-inflammatory lesions (open and closed comedones).

5. Subject and parent/guardian (if applicable) are willing to comply with study instructions and return to the clinic for required visits.

6. Subject has used the same type and brand of make-up, other facial products (exclusive of RX/OTC acne cleansers) and hair products (e.g., shampoo, gel, hair spray, mousse, etc.) for at least one (1) month prior to the Baseline Visit and agrees to continue his/her other general skin and hair care products and regimen for the entire study.

Exclusion Criteria:

1. Subject is pregnant, lactating, or is planning to become pregnant during the study.

2. Subject has any skin pathology or condition that could interfere with the evaluation of the test products or requires the use of interfering topical or systemic therapy.

3. Subject has greater than two (2) facial nodules.

4. Subject has nodulocystic acne.

5. Subject has any condition which, in the investigator's opinion, would make it unsafe for the subject to participate in this research study.

6. Subject is currently enrolled in an investigational drug or device study.

7. Subject has received an investigational drug or has been treated with an investigational device within 30 days prior to the initiation of treatment (Baseline).

8. Subject has facial hair that could interfere with the study assessments in the opinion of the investigator.

9. Subject and parent/guardian (if applicable) are unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function.

10. Subject may be unreliable for the study including subjects who engage in excessive alcohol intake or drug abuse, or subjects who are unable to return for scheduled follow-up visits.

11. Subject has known hypersensitivity or previous allergic reaction to any of the active or inactive components of the test articles.

12. Subject has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the trial.

13. Subject has used any of the prohibited topical anti-acne treatments or procedures prior to the study unless appropriate washout period is documented.

14. Subject has used used any of the prohibited systemic anti-acne medications prior to the study unless appropriate washout period is documented.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clear dermatology & Aesthetic Center	Scottsdale	Arizona	United States	85255
2	Johnson Dermatology	Fort Smith	Arkansas	United States	72916
3	Center for Dermatology and Laser Surgery	Sacramento	California	United States	95819
4	Belleair Research Center	Pinellas Park	Florida	United States	33781
5	Arlington Dermatology	Arlington Heights	Illinois	United States	60005
6	Kansas City Dermatology, PA	Overland Park	Kansas	United States	66215
7	Maryland Laser Skin and Vein Institute	Hunt Valley	Maryland	United States	21030
8	Sadick Research Group, LLC	New York	New York	United States	10075
9	Skin Specialty Dermatology	New York	New York	United States	10155
10	Clinical Partners, LLC	Johnston	Rhode Island	United States	02919
11	Texas Dermatology and Laser Specialists	San Antonio	Texas	United States	78218
12	Progressive Clinical Research, PA	San Antonio	Texas	United States	78229
13	Site 3521	Plovdiv		Bulgaria	4000
14	Site 3523	Sofia		Bulgaria	1000
15	Site 3525	Sofia		Bulgaria	1404
16	3520	Sofia		Bulgaria	1407
17	Site 3524	Sofia		Bulgaria	1407
18	Site 3519	Sofia		Bulgaria	1431
19	Site 3526	Sofia		Bulgaria	1618
20	Site 3522	Varna		Bulgaria	9010
21	Site 9923	Batumi		Georgia	6010
22	Site 9924	Kutaisi		Georgia	4600
23	Site 9921	Tbilisi		Georgia	0145
24	Site 9920	Tbilisi		Georgia	0177
25	Site 9922	Tbilisi		Georgia	0186
26	Site 9925	Zugdidi		Georgia	2100
27	4819	Bydgoszcz		Poland	85-863
28	Site 4814	Czestochowa		Poland	15-794
29	Site 4822	Czestochowa		Poland	42-217
30	4815	Katowice		Poland	40-611
31	Site 4811	Katowice		Poland	62-069
32	Site 4821	Kraków		Poland	30-002
33	Site 4815	Kraków		Poland	40-611
34	Site 4813	Kraków		Poland	70-332
35	Site 4823	Osielsko		Poland	86-031
36	Site 4816	Rzeszów		Poland	61-113
37	Site 4812	Szczecin		Poland	51-685
38	Site 4818	Warszawa		Poland	02-106
39	Site 4820	Łódź		Poland	91-334
40	Site 4033	Sector 2	Bucharest	Romania	020125
41	Site 4034	Sector 2	Bucharest	Romania	020125
42	Site 4031	Sector 3	Bucharest	Romania	030303
43	Site 4029	Sector 6	Bucharest	Romania	062272
44	Site 4028	Târgovişte	Jud. Dambovita	Romania
45	Site 4036	Bucarest		Romania	010825
46	Site 4035	Bucharest		Romania	011025
47	Site 4032	Craiova		Romania	200642
48	Site 4037	Iaşi		Romania	700381
49	Site 4030	Sibiu		Romania	550245
50	Site 8138	Belgrade		Serbia	11050
51	Site 8137	Belgrade		Serbia	8137
52	Site 8136	Novi Sad		Serbia	21000

Sponsors and Collaborators

• Cassiopea SpA

Investigators

• Study Director: R&D Cassiopea, Cassiopea S.p.A.

Study Documents (Full-Text)

• Study Protocol - Jun 11, 2015
• Statistical Analysis Plan - May 29, 2018

More Information

Additional Information:

• Study Website

Publications

None provided.

• Responsible Party: Cassiopea SpA
• ClinicalTrials.gov Identifier: NCT02608476
• Other Study ID Numbers: CB-03-01/26
• First Posted: Nov 18, 2015
• Last Update Posted: Nov 20, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Cassiopea SpA: acne; clascoterone; anti-androgen
• Additional relevant MeSH terms: Acne Vulgaris

Study Results

Participant Flow

Arm/Group Title	CB-03-01 Cream	Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
Period Title: Overall Study
STARTED	369	363
COMPLETED	302	282
NOT COMPLETED	67	81

Baseline Characteristics

Arm/Group Title	CB-03-01 Cream	Vehicle Cream	Total
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.	Total of all reporting groups
Overall Participants	369	363	732
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	19.3 (5.6)	19.0 (5.4)	19.2 (5.5)
Sex: Female, Male (Count of Participants)
Female	243 65.9%	221 60.9%	464 63.4%
Male	126 34.1%	142 39.1%	268 36.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 5.4%	9 2.5%	29 4%
Not Hispanic or Latino	349 94.6%	354 97.5%	703 96%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%	1 0.3%	2 0.3%
Asian	0 0%	4 1.1%	4 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.3%	1 0.1%
Black or African American	7 1.9%	6 1.7%	13 1.8%
White	357 96.7%	348 95.9%	705 96.3%
More than one race	0 0%	1 0.3%	1 0.1%
Unknown or Not Reported	4 1.1%	2 0.6%	6 0.8%
Baseline IGA (Count of Participants)
0 - Clear	0 0%	0 0%	0 0%
1 - Almost Clear	0 0%	0 0%	0 0%
2 - Mild	0 0%	0 0%	0 0%
3 - Moderate	305 82.7%	313 86.2%	618 84.4%
4 - Severe	64 17.3%	50 13.8%	114 15.6%
Baseline Acne Lesion Counts (lesions) [Mean (Standard Deviation) ]
Non-inflammatory lesions	62.8 (21.4)	63.3 (20.5)	63.1 (21.0)
Inflammatory lesions	42.9 (12.2)	41.3 (11.0)	42.1 (11.6)
Total Lesions	105.7 (25.8)	104.6 (24.2)	105.2 (25.0)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Success in Investigator's Global Assessment (IGA)
Description	Percentage of subjects in each treatment group achieving "success" at Week 12, with "success" defined as an IGA score of "clear (score=0)" or "almost clear (score=1)" and at least a two-point reduction in IGA compared to Baseline.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population, which included all randomized subjects

Arm/Group Title	CB-03-01 Cream	Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
Measure Participants	369	363
Number [Percentage of subjects]	20.3	6.5

2. Primary Outcome

Title	Change From Baseline in Non-inflammatory Lesion (NIL) Counts
Description	Absolute change from Baseline in non-inflammatory lesion counts in each treatment group at Week 12.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	CB-03-01 Cream	Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
Measure Participants	369	363
Mean (95% Confidence Interval) [Non-inflammatory lesions]	-19.4	-10.8

3. Primary Outcome

Title	Change From Baseline in Inflammatory Lesion (IL) Counts
Description	Absolute change from Baseline in inflammatory lesion counts in each treatment group at Week 12.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	CB-03-01 Cream	Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
Measure Participants	369	363
Mean (95% Confidence Interval) [Inflammatory lesions]	-20.0	-12.6

4. Secondary Outcome

Title	Change From Baseline in Total Lesion Counts
Description	Absolute change from Baseline in total lesions counts in each treatment group at Week 12.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	CB-03-01 Cream	Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
Measure Participants	369	363
Mean (95% Confidence Interval) [total lesions]	-40.0	-23.6

5. Secondary Outcome

Title	Percent Change From Baseline in Total Lesion Counts
Description	Percent change from Baseline in total lesions counts in each treatment group at Week 12.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	CB-03-01 Cream	Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
Measure Participants	369	363
Mean (95% Confidence Interval) [percent change]	-37.3	-22.1

6. Secondary Outcome

Title	Percent Change From Baseline in Non-inflammatory Lesion Counts
Description	Percent change from Baseline in non-inflammatory lesions count in each treatment group at Week 12.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	CB-03-01 Cream	Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
Measure Participants	369	363
Mean (95% Confidence Interval) [percent change]	-29.3	-15.6

7. Secondary Outcome

Title	Percent Change From Baseline in Inflammatory Lesion Counts
Description	Percent change from Baseline in inflammatory lesions count in each treatment group at Week 12.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	CB-03-01 Cream	Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.	Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
Measure Participants	369	363
Mean (95% Confidence Interval) [percent change]	-46.9	-29.6

8. Other Pre-specified Outcome

Title	Local Site Reactions
Description	Local Site Reactions (LSRs) including telangiectasia, skin atrophy, striae rubrae, erythema, edema, scaling/dryness, stinging/burning, and pruritus scored by frequency and severity at every visit (Baseline, Weeks 4, 8, and 12).
Time Frame	Baseline, Weeks 4, 8, and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events (AEs) and serious adverse events (SAEs) were collected from screening visit, Baseline (Day 1) and up to Week 12/early termination.
Adverse Event Reporting Description	The Safety population was used for all analyses which comprised of all participants enrolled in the study and applied at least on dose of the test article.
Arm/Group Title	CB-03-01 Cream		Vehicle Cream
Arm/Group Description	CB-03-01 cream, 1% applied twice daily for 12 weeks Cortexolone 17α-propionate (USAN/INN: clascoterone) is a steroidal antiandrogen that is being developed as a 1% cream for the topical treatment of acne vulgaris.		Vehicle cream applied twice daily for 12 weeks Vehicle cream: Vehicle cream manufactured to mimic look and feel of CB-03-01 but without the active ingredient cortexolone 17α-propionate.
All Cause Mortality
	CB-03-01 Cream		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/369 (0%)		0/363 (0%)
Serious Adverse Events
	CB-03-01 Cream		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/369 (0%)		1/363 (0.3%)
Vascular disorders
Haematoma	0/369 (0%)	0	1/363 (0.3%)	1
Other (Not Including Serious) Adverse Events
	CB-03-01 Cream		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/369 (5.7%)		34/363 (9.4%)
Gastrointestinal disorders
Diarrhoea	2/369 (0.5%)	2	3/363 (0.8%)	3
General disorders
Pyrexia	0/369 (0%)	0	3/363 (0.8%)	3
Infections and infestations
Nasopharyngitis	3/369 (0.8%)	3	7/363 (1.9%)	10
Upper respiratory tract infection	1/369 (0.3%)	1	4/363 (1.1%)	4
Bronchitis	3/369 (0.8%)	3	0/363 (0%)	0
Nervous system disorders
Headache	4/369 (1.1%)	4	3/363 (0.8%)	3
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	3/369 (0.8%)	3	5/363 (1.4%)	5
Cough	0/369 (0%)	0	3/363 (0.8%)	3
Oropharyngeal pain	4/369 (1.1%)	4	4/363 (1.1%)	6
Skin and subcutaneous tissue disorders
Acne	1/369 (0.3%)	1	3/363 (0.8%)	3

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.