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

A Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of BTX 1503 in Patients With Moderate to Severe Acne Vulgaris

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.

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.

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:

   1. 20 to 50 (inclusive) inflammatory lesions on the face
   2. 20 to 100 (inclusive) non-inflammatory lesions on the face
   3. An Investigator's Global Assessment (IGA) score for acne severity of 3 or 4 (moderate or severe) assessed on the face.

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

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

9. 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.

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

11. 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.

12. 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.

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

    a. 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 c. Two barrier forms of contraception (listed below) i. Male or female condom; diaphragm; cervical cap.

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

15. 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.