Inclusion Criteria:
1. Males and females age 12 years and older
2. Participants (and/or parents or guardians) willing and able to provide informed consent/assent and to comply with the study protocol
3. Clinical diagnosis of moderate to severe facial acne vulgaris defined as the following at Screening and Baseline:
1. IGA 3-4, and;
2. ≥20 to ≤100 inflammatory lesions (papules, pustules, nodules), and;
3. ≥30 to ≤150 non-inflammatory lesions (open comedones or blackheads, closed comedones or whiteheads), and
4. ≤2 nodules, and
5. 0 cysts
4. Willing to refrain from using any acne treatments other than the investigational product for the duration of the study
5. Willing and able to complete once-daily eDiary entries within a consistent timeframe for the duration of the study
6. Judged to be in good health in the Investigator's opinion
7. Ability and willingness to abstain from taking medications not allowed by the protocol for the duration of the study
Exclusion Criteria:
1. Use of topical acne treatments, including benzoyl peroxide within 2 weeks prior to randomization to end of follow-up, retinoids (e.g., tretinoin, tazarotene, adapalene, trifarotene) within 4 weeks prior to randomization to end of follow up, antibiotics (e.g., clindamycin, erythromycin, dapsone), and combinations thereof, within 2 weeks prior to randomization to end of follow-up
2. Use of oral/systemic acne treatments, including antibiotics (e.g., minocycline, doxycycline, tetracycline, erythromycin, trimethoprim sulfamethoxazole, dapsone) within 4 weeks prior to randomization to end of follow-up, retinoid (e.g., isotretinoin or its derivatives) within 6 months prior to randomization to end of follow-up, vitamin A (retinol) supplements greater than 10,000 units/day within 4 weeks prior to randomization to end of follow-up, and zinc within 4 weeks prior to randomization to end of follow-up
3. Use of oral/systemic androgen receptor blockers (such as spironolactone, flutamide, cyproterone acetate, or bicalutamide) within 3 months prior to randomization to end of follow-up
4. Use of topical androgen receptor blockers (such as clascoterone) within 4 weeks prior to randomization to end of follow-up
5. Use of over-the-counter topical medications for the treatment of acne vulgaris including benzoyl peroxide, topical anti-inflammatory medications, corticosteroids, or topical probiotics within 2 weeks prior to randomization to end of follow-up
6. Use of systemic corticosteroids within 4 weeks prior to randomization to end of follow-up
7. Any clinically significant changes in type, dose, or frequency of bland emollients throughout the study from screening to follow-up
8. Use of photodynamic therapy, UV phototherapy, laser therapy of any type, chemical peels, microdermabrasion, comedone extraction, intralesional corticosteroid injections, or other procedural acne treatment on the face within 3 months prior to randomization to end of follow-up
9. Treatment with systemic immunosuppressive/ immunomodulatory therapies within 4 weeks prior to randomization (including but not limited to cyclosporine, mycophenolate-mofetil, methotrexate, azathioprine, interferon gamma)
10. Use of medications known to cause or exacerbate acneiform eruptions including lithium, anabolic steroids, adrenocorticotropic hormone, halogenated compounds, phenytoin, JAK/TYK-2 inhibitors, tapinarof or other aryl hydrocarbon receptor (AhR) agonists used for dermatological indications, EGFR inhibitors, mTOR inhibitors, or high-dose standalone vitamin B12 supplementation within 4 weeks prior to randomization to end of follow-up; standard multivitamin formulations are permitted
11. Use of any non-steroidal and non-immunomodulatory topical treatment for acne (other than bland emollient that will be continued during the study period) within 2 weeks prior to randomization to end of follow-up
12. Use of an indoor tanning facility, or outdoor intense sun exposure, sunbathing, or suntanning within 4 weeks prior to randomization to end of follow-up
13. Treatment with any investigational therapy within 4 weeks prior to randomization to end of follow-up
14. Allergen immunotherapy within 6 months prior to randomization to end of follow-up
15. Use of acne-specific skin care products within 2 weeks prior to randomization to end of follow-up
16. Use of traditional Chinese medicine for acne within 2 weeks prior to randomization to end of follow-up
17. Use of keratolytic or peeling agents (e.g., a-hydroxy acid, glycolic acid, salicylic acid, azelaic acid) within 2 weeks prior to randomization to end of follow-up
18. Concurrent skin diseases affecting efficacy evaluation (e.g., dermatitis, psoriasis, rosacea)
19. Nodulocystic acne, secondary acne (e.g., occupational or steroid- induced acne, chloracne, acne mechanica), acne conglobata, acne fulminans, or any other acne variant
20. Facial hair hindering acne assessment
21. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator, contraindicates their participation
22. Commencement of new hormonal therapy or dose change to hormonal therapy within 90 days prior to Baseline. Dose and frequency of use of any hormonal therapy started more than 90 days prior to Baseline must remain unchanged throughout the study. Hormonal therapies include, but are not limited to, oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (e.g., vaginal ring or transdermal hormone contraception)
23. History of malignancy within 5 years prior to randomization, with the exception of completely treated and non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin
24. History of a major psychiatric condition (including major depressive disorder, bipolar disorder, or schizophrenia), suicidal ideation, or suicide attempt
25. Known active hepatitis infection
26. Known history of human immunodeficiency virus (HIV) infection
27. Presence of any clinically significant systemic disease, laboratory abnormality, medical condition or disability that, in the Investigator's opinion, could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the participant
28. Currently pregnant or breastfeeding, or male participant with a pregnant or breastfeeding partner
29. Females of childbearing potential who are unable or unwilling to practice highly effective contraception (pregnancy prevention); fertile males who are unable or unwilling to use condoms with female partners of childbearing potential
30. The participant has been previously randomized in this study
31. Inability to give informed consent
