Evaluation of BTX 1503 in Patients With Moderate to Severe Acne Vulgaris

• Sponsor: Botanix Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03573518
• Collaborator: (none)
• Enrollment: 368
• Locations: 36
• Arms: 5
• Actual Duration (Months): 14.3
• Patients Per Site: 10.2
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The objective of this study is to assess safety and efficacy of various doses of BTX 1503 liquid formulation in subjects with moderate to severe acne vulgaris of the face.

Condition or Disease	Intervention/Treatment	Phase
Acne Vulgaris	Drug: BTX 1503; Drug: Vehicle	Phase 2

Detailed Description

This will be a multi-center, randomized, double-blinded, vehicle-controlled, parallel group, dose-finding study in pediatrics, adolescents and adults (aged 12 to 40 years). The objective of this study is to assess the safety and efficacy of various doses of BTX 1503 in subjects with moderate to severe acne vulgaris of the face.

Study Design

• Study Type: Interventional
• Actual Enrollment: 368 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of BTX 1503 in Patients With Moderate to Severe Acne Vulgaris
• Actual Study Start Date: Jun 26, 2018
• Actual Primary Completion Date: Aug 16, 2019
• Actual Study Completion Date: Sep 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BTX 1503 5% BID BTX 1503 5% CBD (w/w) solution twice daily	Drug: BTX 1503; BTX 1503 Dose 1 liquid formulation, or BTX 1503 Dose 2 liquid formulation; Other Names: BTX1503
Experimental: BTX 1503 5% QD BTX 1503 5% CBD (w/w) solution once daily	Drug: BTX 1503; BTX 1503 Dose 1 liquid formulation, or BTX 1503 Dose 2 liquid formulation; Other Names: BTX1503
Experimental: BTX 1503 2.5% QD BTX 1503 2.5% CBD (w/w) solution once daily	Drug: BTX 1503; BTX 1503 Dose 1 liquid formulation, or BTX 1503 Dose 2 liquid formulation; Other Names: BTX1503
Placebo Comparator: Vehicle BID Vehicle twice daily	Drug: Vehicle; Placebo
Placebo Comparator: Vehicle QD Vehicle once daily	Drug: Vehicle; Placebo

Outcome Measures

Primary Outcome Measures

1. Safety as Measured by Reported Adverse Events [Day 84]

   Summary of Treatment-Emergent Adverse Events by MedDra Preferred Term that Occurred with a Frequency > 2% in any Treatment Group (Safety Population)

Secondary Outcome Measures

1. Absolute Change From Baseline in Inflammatory Lesion Counts [Day 84]

   Summary of Absolute Change from Baseline in Inflammatory Count at Day 84 (Intent-to-Treat Population)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject (or legal guardian) has the ability and willingness to sign a written informed consent/assent.

2. Subject is of either gender and 12 to 40 years of age.

3. Subject is in good general health without clinically significant haematological, cardiac, respiratory, renal, endocrine, gastrointestinal, psychiatric, hepatic, or malignant disease, as determined by the investigator.

4. Subject has suitable venous access for blood sampling.

5. Subject is able and willing to complete the study and to comply with all study instructions and attend the necessary visits.

6. Subject has acne vulgaris of the face defined as:

7. 20 to 50 (inclusive) inflammatory lesions on the face

8. 20 to 100 (inclusive) non-inflammatory lesions on the face

9. An Investigator's Global Assessment (IGA) score for acne severity of 3 or 4 (moderate or severe) assessed on the face.

10. Subject has ≤ 2 nodular/cystic acne lesions (>5 mm in diameter).

11. Subject must refrain from the use of other treatments for acne during the study.

12. Subject must agree to not wash or shave their face, swim or otherwise get their face wet for at least 1 hour after application of study medication.

13. Subject must agree to maintain their regular use of sunscreens, moisturizers, shaving cream, and facial make up throughout the entire course of the study.

14. Male subjects and their partners must agree and commit to use a barrier method of contraception during the study and for 90 days after last study drug application.

15. A negative UPT result for all WOCBP at the Screening Visit and Baseline Visit, if applicable. A WOCBP is one who is not permanently sterilized or is not postmenopausal. Postmenopausal is defined as 24 months with no menses without an alternative medical cause.

16. Sexually active women must agree to use the following throughout the study and for 30 days after last study drug application:

1. One of these highly effective contraception methods i. Intrauterine device (IUD); hormonal (injections, implants, transdermal patch, vaginal ring; tubal ligation; partner vasectomy, OR b. Oral contraceptives WITH a barrier method (listed below), OR
2. Two barrier forms of contraception (listed below) i. Male or female condom; diaphragm; cervical cap.

1. Male subjects must refrain from sperm donation during the study treatment period until 90 days after final study drug administration.

2. Male subjects must agree to keep their face clean shaven (no moustache or goatee; short sideburns acceptable) throughout the study and use the same method for shaving as was used for the 4 weeks prior to the Screening Visit.

Exclusion Criteria:

1. People who would otherwise qualify for the study but are living in the same household as a study subject, are not allowed to participate in the study.

2. Female subject who is breast feeding, pregnant, or planning to become pregnant any time during the course of the study.

3. Subject with history of known or suspected intolerance to the drug product excipients.

4. Subject has known HIV infection.

5. Subject has acne conglobata, acne fulminans, secondary acne (chloracne), pseudo-folliculitis, severe acne requiring systemic treatment, or is taking a medication known to induce or exacerbate acne.

6. Subject has severe truncal acne.

7. Subject has excessive facial hair that would interfere with the evaluation of safety or with the diagnosis or assessment of acne vulgaris.

8. Subject has sunburns, unevenness in skin tones, tattoos, scars, excessive hair, freckles, birthmarks, moles, or other skin damage or abnormality that would result in the inability to evaluate the skin of the face.

9. Subject has any skin condition of the face other than acne vulgaris.

10. Subject has used oral retinoid (e.g. isotretinoin) within 6 months (180 days) prior to the Baseline Visit.

11. Subject has used Vitamin A supplements greater than 10,000 units/day within 6 months (180 days) prior to the Baseline Visit.

12. Subject has used androgen receptor blockers (such as spironolactone or flutamide) within 3 months (90 days) prior to the Baseline Visit.

13. Subject has initiated treatment with hormonal therapy or changed dosing with hormonal therapy within 3 months (90 days) prior to the Baseline Visit.

14. Subject has had facial procedures (chemical or laser peel, microdermabrasion, etc.) within 8 weeks (56 days) prior to the Baseline Visit.

15. Subject has had treatment with systemic antibiotics within 4 weeks (28 days) prior to the Baseline Visit.

16. Subject has had treatment with systemic anti-acne drugs within 4 weeks (28 days) prior to the Baseline Visit.

17. Subject has had treatment with systemic anti-inflammatory drugs within 4 weeks (28 days) prior to the Baseline Visit.

18. Subject has had treatment with systemic (oral) corticosteroids other immunosuppressive medications within 4 weeks (28 days) prior to the Baseline Visit.

19. Subject has had treatment with prescription topical retinoid use on the face (e.g. tretinoin, tazarotene) within 4 weeks (28 days) prior to the Baseline Visit.

20. Subject has had treatment with topical prescription antibiotics (e.g. dapsone, clindamycin, erythromycin, or sulfacetamide) or combination products that include a topical antibiotic within 2 weeks (14 days) prior to the Baseline Visit.

21. Subject has had treatment with over-the-counter (OTC) topical medications for the treatment of acne vulgaris including benzoyl peroxide, topical anti- inflammatory medications, corticosteroids, adapalene, α-hydroxy/glycolic acid on the face within 2 weeks (14 days) prior to the Baseline Visit.

22. Subject is currently using any medication that, in the opinion of the investigator, may affect the evaluation of the study product or place the subject at undue risk.

23. Subject has had photodynamic therapy within 8 weeks (56 days) prior to the Baseline Visit.

24. Subject has used a tanning bed within 2 weeks (14 days) prior to the Baseline Visit.

25. Subject has used home-based light treatment within 2 weeks (14 days) prior to the Baseline Visit.

26. Subject has an underlying disease that requires the use of interfering topical or systemic therapy.

27. Subject has other dermatological conditions that require the use of interfering topical or systemic therapy or that might interfere with study assessments such as, but not limited to, atopic dermatitis, psoriasis, perioral dermatitis, or rosacea.

28. Subject has had excessive sun exposure (in the opinion of the investigator) within one week prior to the Baseline Visit and an unwillingness to refrain from excessive sun exposure during the study.

29. Subject has a clinically relevant history or currently suffering from any disease or condition that, in the opinion of the investigator, may affect the evaluation of the study product or place the subject at undue risk. This may include respiratory (including chronic asthma requiring repetitive drug interventions), gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, or connective tissue diseases or disorders.

30. Subject has a clinically relevant history of, or current evidence of, abuse of alcohol or other drugs. Subjects may be deemed eligible if the UDS identifies subject-reported, prescribed drugs or appropriate levels of alcohol, as determined by the investigator.

31. Subject has participated in another investigational drug or device research study within 4 weeks (28 days) of the Baseline Visit or five half-lives of the drug, whichever is longer.

32. Any other reason that would make the subject, in the opinion of the investigator or sponsor, unsuitable for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Applied Research Center of Arkansas	Little Rock	Arkansas	United States	72212
2	Encino Research Center	Encino	California	United States	91436
3	Dermatology Specialist, Inc.	Murrieta	California	United States	92562
4	Quest Dermatology Research	Northridge	California	United States	91324
5	Clinical Science Insitute	Santa Monica	California	United States	90404
6	Well Phrama Medical Research	Miami	Florida	United States	33143
7	Tory Sullivan, M.D., PA	North Miami Beach	Florida	United States	33162
8	Precision Clinical Research	Sunrise	Florida	United States	33351
9	DS Research - Louisville	Louisville	Kentucky	United States	40241
10	Delricht Research	New Orleans	Louisiana	United States	70115
11	Metro Boston Clinical	Brighton	Maine	United States	02135
12	Minnesota Clinical Study Center	Fridley	Minnesota	United States	55432
13	Medisearch Clinical Trials	Saint Joseph	Missouri	United States	64506
14	Washington University School of Medicine - Dermatology	Saint Louis	Missouri	United States	63141
15	JDR Dermatology Research	Las Vegas	Nevada	United States	89148
16	The Acne Treatment and Research Center	Morristown	New Jersey	United States	07960
17	Aventiv Research	Dublin	Ohio	United States	43016
18	Penn State Hershey Medical	Hershey	Pennsylvania	United States	17033
19	Clinical Partners, LLC	Johnston	Rhode Island	United States	02919
20	Greenville Dermatology, LLC	Greenville	South Carolina	United States	29607
21	Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	29464
22	Avant Research Associates, LLC	Austin	Texas	United States	78704
23	DermReasearch	Austin	Texas	United States	78759
24	J&S Studies, Inc.	College Station	Texas	United States	77845
25	Suzanne Bruce and Associates, PA	Houston	Texas	United States	77056
26	Cmax Clinical Research	Adelaide		Australia	5000
27	The Skin Centre	Benowa		Australia	4217
28	Burswood Dermatology	Burwood		Australia	6100
29	Skin & Canver Foundation Inc.	Carlton		Australia	053
30	Sinclair Dermatology	East Melbourne		Australia	3002
31	Fremantle Dermatology	Fremantle		Australia	6160
32	North Eastern Health Specialist	Hectorville		Australia	5073
33	St George Dermatology & Skim Cancer Center	Kogarah		Australia	2217
34	Captain Sterline Medical Centre	Nedlands		Australia	6009
35	Woden Dermatology	Phillip		Australia	2606
36	Varacity Clinical Research	Woolloongabba		Australia	4102

Sponsors and Collaborators

• Botanix Pharmaceuticals

Investigators

• Study Director: Anthony Robinson, CRNP, Head of Development, Botanix Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Jun 7, 2018
• Statistical Analysis Plan - May 24, 2019

More Information

Publications

None provided.

• Responsible Party: Botanix Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03573518
• Other Study ID Numbers: BTX.2018.001
• First Posted: Jun 29, 2018
• Last Update Posted: Apr 18, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Botanix Pharmaceuticals: Synthetic CBD; Cannabidiol
• Additional relevant MeSH terms: Acne Vulgaris

Study Results

Participant Flow

Arm/Group Title	BTX 1503 5% BID	BTX 1503 5% QD	BTX 1503 2.5% QD	Vehicle Combined (BID or QID)
Arm/Group Description	BTX 1503 5% CBD (w/w) solution twice daily	BTX 1503 5% CBD (w/w) solution once daily	BTX 1503 2.5% CBD (w/w) solution once daily	Placebo BID + Placebo QD =Placebo Combined group
Period Title: Overall Study
STARTED	92	92	92	92
COMPLETED	69	77	70	81
NOT COMPLETED	23	15	22	11

Baseline Characteristics

Arm/Group Title	BTX 1503 5% BID	BTX 1503 5% QD	BTX 1503 2.5% QD	Vehicle Combined (BID or QID)	Total
Arm/Group Description	BTX 1503 5% CBD (w/w) solution twice daily	BTX 1503 5% CBD (w/w) solution once daily	BTX 1503 2.5% CBD (w/w) solution once daily	Placebo BID + Placebo QD =Placebo Combined group	Total of all reporting groups
Overall Participants	92	92	92	92	368
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	19.5 (6.65)	19.7 (5.99)	19.4 (5.98)	20.5 (6.14)	20.0 (6.17)
Sex: Female, Male (Count of Participants)
Female	56 60.9%	60 65.2%	58 63%	55 59.8%	229 62.2%
Male	36 39.1%	32 34.8%	34 37%	37 40.2%	139 37.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	26 28.3%	21 22.8%	23 25%	23 25%	93 25.3%
Not Hispanic or Latino	66 71.7%	71 77.2%	69 75%	69 75%	275 74.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.1%	0 0%	0 0%	1 0.3%
Asian	5 5.4%	5 5.4%	5 5.4%	7 7.6%	22 6%
Native Hawaiian or Other Pacific Islander	3 3.3%	0 0%	1 1.1%	1 1.1%	5 1.4%
Black or African American	12 13%	5 5.4%	5 5.4%	6 6.5%	28 7.6%
White	67 72.8%	75 81.5%	73 79.3%	72 78.3%	287 78%
More than one race	5 5.4%	6 6.5%	8 8.7%	6 6.5%	25 6.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Inflammatory Lesion Count (Lesions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Lesions]	29.3 (8.52)	28.5 (8.95)	29.6 (8.00)	29.1 (8.25)	29.1 (8.37)

Outcome Measures

1. Primary Outcome

Title	Safety as Measured by Reported Adverse Events
Description	Summary of Treatment-Emergent Adverse Events by MedDra Preferred Term that Occurred with a Frequency > 2% in any Treatment Group (Safety Population)
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	BTX 1503 5% BID	BTX 1503 5% QD	BTX 1503 2.5% QD	Vehicle Combined (BID or QID)
Arm/Group Description	BTX 1503 5% CBD (w/w) solution twice daily	BTX 1503 5% CBD (w/w) solution once daily	BTX 1503 2.5% CBD (w/w) solution once daily	Placebo BID + Placebo QD =Placebo Combined group
Measure Participants	92	91	91	91
Upper Respiratory tract infection	2	4	5	5
Viral upper respiratory tract infection	3	2	3	4
Headache	1	1	2	0
Acne	2	0	2	0
Cough	1	0	2	0
Oropharyngeal pain	0	2	0	1

2. Secondary Outcome

Title	Absolute Change From Baseline in Inflammatory Lesion Counts
Description	Summary of Absolute Change from Baseline in Inflammatory Count at Day 84 (Intent-to-Treat Population)
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population

Arm/Group Title	BTX 1503 5% BID	BTX 1503 5% QD	BTX 1503 2.5% QD	Vehicle Combined (BID or QID)
Arm/Group Description	BTX 1503 5% CBD (w/w) solution twice daily	BTX 1503 5% CBD (w/w) solution once daily	BTX 1503 2.5% CBD (w/w) solution once daily	Placebo BID + Placebo QD =Placebo Combined group
Measure Participants	92	92	91	92
Least Squares Mean (Standard Deviation) [Lesions]	-8.5 (12.57)	-12 (12.58)	-11.7 (12.57)	-11.3 (12.57)

Adverse Events

Time Frame	Approximately 3 months
Adverse Event Reporting Description	Reporting of AE's included reporting of pregnancy
Arm/Group Title	BTX 1503 5% BID		BTX 1503 5% QD		BTX 1503 2.5% QD		Vehicle Combined (BID or QID)
Arm/Group Description	BTX 1503 5% CBD (w/w) solution twice daily		BTX 1503 5% CBD (w/w) solution once daily		BTX 1503 2.5% CBD (w/w) solution once daily		Placebo BID + Placebo QD =Placebo Combined group
All Cause Mortality
	BTX 1503 5% BID		BTX 1503 5% QD		BTX 1503 2.5% QD		Vehicle Combined (BID or QID)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		0/91 (0%)		0/91 (0%)		0/91 (0%)
Serious Adverse Events
	BTX 1503 5% BID		BTX 1503 5% QD		BTX 1503 2.5% QD		Vehicle Combined (BID or QID)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		0/91 (0%)		0/91 (0%)		0/91 (0%)
Other (Not Including Serious) Adverse Events
	BTX 1503 5% BID		BTX 1503 5% QD		BTX 1503 2.5% QD		Vehicle Combined (BID or QID)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/92 (9.8%)		9/91 (9.9%)		14/91 (15.4%)		10/91 (11%)
Gastrointestinal disorders
Oorpharyngeal Pain	0/92 (0%)	0	2/91 (2.2%)	2	0/91 (0%)	0	1/91 (1.1%)	1
Nervous system disorders
Headache	1/92 (1.1%)	1	1/91 (1.1%)	1	2/91 (2.2%)	2	0/91 (0%)	0
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	2/92 (2.2%)	2	4/91 (4.4%)	4	5/91 (5.5%)	5	5/91 (5.5%)	5
Viral upper respiratory tract infection	3/92 (3.3%)	3	2/91 (2.2%)	2	3/91 (3.3%)	3	4/91 (4.4%)	4
Cough	1/92 (1.1%)	1	0/91 (0%)	0	2/91 (2.2%)	2	0/91 (0%)	0
Skin and subcutaneous tissue disorders
Acne	2/92 (2.2%)	2	0/91 (0%)	0	2/91 (2.2%)	2	0/91 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

As Study is a Multi-centre Study, no Publication of the Study results may be made until Publication of the results of the Multi-centre study or 2 years after Study Completion, whichever is sooner.