| Eligibility |
Inclusion Criteria:
1. Male or non-pregnant, non-lactating female aged = 12 and = 40 years with a clinical
diagnosis of acne vulgaris.
2. Subjects who are 18 years of age or older (up to the age of 40) must have provided
IRB/IEC approved written informed consent. Subjects 12 to 17 years of age inclusive
must have provided IRB/IEC approved written assent; this written assent must be
accompanied by an IRB/IEC approved written informed consent from the Subject's legally
acceptable representative (i.e., parent or guardian). In addition, all Subjects or
their legally acceptable representatives (i.e., parent or guardian) must sign a HIPAA
authorization.
3. Subjects must have = 25 non-inflammatory lesions (i.e., open and closed comedones) AND
= 20 inflammatory lesions (i.e., papules and pustules) AND = 2 nodulocystic lesions
(i.e.,nodules and cysts), at screening/baseline on the face.
(a) For the purposes of study treatment and evaluation, these lesions should be
limited to the facial treatment area. All lesions will be counted, including those
present on the nose. Subjects may have acne lesions on other areas of the body which
will be excluded from the count and the Investigator's Global Assessment (IGA)
evaluation (e.g., on the back, chest and arms).
4. Subjects must have a definite clinical diagnosis of acne vulgaris severity grade 2, 3,
or 4 as per the Investigator's Global Assessment (IGA) (per Table 1 below) at
screening/baseline. Acne vulgaris should be stable (for at least 3 months prior to
screening), with minimal variation from day to day and within each day, in the opinion
of the subject.
Table 1: Investigator's Global Assessment (IGA) Scale for Acne Vulgaris Grade
Description 0 Clear skin with no inflammatory or non-inflammatory lesions 1 Almost
clear; rare non-inflammatory lesions with no more than one small inflammatory lesion 2
Mild severity; greater than Grade 1; some non-inflammatory lesions with no more than a
few inflammatory lesions (papules/pustules only, no nodular lesions) 3 Moderate
severity; greater than Grade 2; up to many noninflammatory lesions and may have some
inflammatory lesions, but no more than one small nodular lesion 4* Severe; greater
than Grade 3; up to many non-inflammatory lesions and may have some inflammatory
lesions, but no more than a few nodular lesions
* The eCRF will allow for reporting by Investigators of lesion worsening beyond Grade
4 with treatment. Acne vulgaris subjects with nodulocystic acne are not to be enrolled
in the study.
Subjects who worsen beyond Grade 4 will be described in the safety evaluation. Note:
Counts of nodules and cysts will be reported separately and not included in the
inflammatory or non-inflammatory lesion counts.
5. Subjects must be willing to refrain from using all other topical acne medications or
antibiotics during the 12-week treatment period, other than the investigational
product.
6. Female subjects of childbearing potential (*WOCBP) must not be pregnant or lactating
at the time of screening/baseline visit as documented by a negative urine pregnancy
test with a sensitivity to at least 25 mIU/ml hCG .
*Female subjects of childbearing potential (WOCBP) are defined as sexually mature
women without prior hysterectomy, or who have had any evidence of menses in the past
12 months.
However, women who have been amenorrheic for the past 12 or more months are still
considered to be of childbearing potential, if the amenorrhea is possibly due to other
causes, including prior chemotherapy, anti- estrogens, or ovarian suppression.
Postmenopausal women (defined as women who have been amenorrheic for at least 12
consecutive months, in the appropriate age group, without other known or suspected
primary cause) or women who have been sterilized surgically or who are otherwise
proven sterile (i.e., total hysterectomy, or bilateral oophorectomy with surgery at
least 4 weeks prior to randomization) are not considered WOCBP. Subjects who have
undergone tubal ligation are NOT considered as surgically sterile.
7. Female subjects of childbearing potential must be willing to use an acceptable form of
birth control during the study from the day of the first dose administration to 30
days after the last administration of study drug.
1. For the purposes of this study the following are considered acceptable methods of
birth control: oral or injectable contraceptives, contraceptive patches,
medroxyprogesterone acetate (ex. Depo-Provera®) with stabilized use for at least
3 months, vaginal contraceptive (ex. etonogestrel/ethinyl estradiol vaginal ring
(ex. NuvaRing®), contraceptive implant with etonogestrel or equivalent, double
barrier methods, (e.g.
condom and spermicide), intrauterine device (IUD), true abstinence (if in line
with subject's lifestyle).
2. If a subject who was abstinent becomes sexually active during the study, a 2nd
acceptable method of birth control should be used and documented.
3. Subjects on hormonal contraception must be stabilized on the same type for at
least three months prior to enrollment in the study and must not change the
method during the study.
A sterile sexual partner is not considered an adequate form of birth control.
8. Female subjects who are premenarchal, surgically sterilized (by *hysterectomy or
bilateral oophorectomy) or postmenopausal for at least 1 year (defined as women who
have been amenorrheic for at least 12 consecutive months, without other known or
suspected primary cause).
9. All male subjects must agree to use accepted methods of birth control with their
partners, from the day of the first dose administration to 30 days after the last
administration of study drug.
True abstinence is an acceptable method of birth control if in line with subject's
lifestyle.
Female partners should use an acceptable method of birth control as described in the
above criteria 7.
10. Subjects must be willing and able to understand and comply with the requirements of
the protocol, including attendance at all required study visits and refraining from
the use of all other topical acne medications or antibiotics during the 12-week
treatment period.
11. Subjects must be in good health and free from any clinically significant disease,
which may interfere with the evaluation of acne vulgaris or the administration of the
investigative product.
12. Subjects who use make-up must have used the same brands/types of make-up for a minimum
period of 14 days prior to study entry and must agree to not change make-up brand/type
or frequency of use throughout the study.
Exclusion Criteria:
1. Female subjects who are pregnant, lactating or planning to become pregnant during
study participation.
2. Subjects with a history of hypersensitivity or allergy to trifarotene, tretinoin,
retinoids, or any of the study medication ingredients.
3. Subjects with the presence of any skin condition that would interfere with the
diagnosis or assessment of acne vulgaris (such conditions include but are not limited
to the following on the face: rosacea, dermatitis, psoriasis, squamous cell carcinoma,
eczema, acneiform eruptions caused by medications, steroid or corticosteroid-induced
acne, steroid folliculitis, or bacterial folliculitis, auto-immune disease, perioral
dermatitis, carcinoid syndrome, mastocytosis, acneiform eruptions caused by make-up
and medication, facial psoriasis and facial eczema).
4. Subjects with nodulocystic acne (> 2 nodules and cysts). [Nodules or cysts defined as;
deepseated in the skin (i.e., centered in the dermis or subcutis) and an inflammatory
lesion greater than or equal to 5 mm in diameter], acne conglobata, acne fulminans,
secondary acne (chloracne, drug-induced acne, etc.) or acne vulgaris requiring
systemic treatment.
5. Subjects with excessive facial hair (e.g., beards, sideburns, moustaches, etc.) that
would interfere with diagnosis or assessment of acne vulgaris.
6. Subjects with tattoos or excessive facial scarring that, in the Investigator's
opinion, may interfere with the evaluation of the patient's acne.
7. Subjects who have used within 6 months prior to screening/baseline oral retinoids
(e.g., Accutane®) or therapeutic vitamin A supplements of greater than 10,000
units/day (multivitamins are allowed). These treatments with oral retinoids or Vitamin
A supplements are prohibited during the study participation.
8. Subjects who have used within 1 month prior to screening/baseline neuromuscular
blocking agents or androgen receptor blockers (e.g., spironolactone, Flutamide etc.).
9. Subjects who have had laser therapy, electrodessication phototherapy and or cosmetic
procedures (e.g., ClearLight ® BOTOX, Filler, micro needling) to the facial area
within 6 months prior to study entry.
10. Subjects who have had facial cosmetic procedures (e.g., facials) or application of
cosmetic products (cosmetics, makeup or facial products that have a strong drying or
possible interactive effect, particularly preparations containing spices, lime sulfur,
resorcinol, or salicylic acid with tretinoin or other retinoids) which may affect the
efficacy and safety profile of the investigational product within 2 weeks prior to
study entry.
11. Subjects who have received radiation therapy and/or anti-neoplastic agents within 3
months prior to screening/baseline.
12. Subjects who have used for less than (<) 3 months prior to screening/baseline
estrogens or oral contraceptives; use of such therapy must remain constant throughout
the study.
13. Subjects who have used any of the following procedures on the face within 1 month
prior to screening/baseline or use during the study:
1. cryodestruction or chemodestruction,
2. dermabrasion,
3. photodynamic therapy,
4. acne surgery,
5. intralesional steroids, or
6. X-ray therapy.
14. Subjects who have used any of the following treatments within 1 month prior to
screening/baseline or during the study:
1. androgen receptor blockers (e.g., spironolactone, Flutamide etc.)
2. systemic steroids,
3. systemic antibiotics,
4. systemic treatment for acne vulgaris (other than oral retinoids, which require a
6-month washout),
5. systemic anti-inflammatory agents. If Subject uses a systemic anti-inflammatory
product during the study, the Principal Investigator will judge if this protocol
deviation is clinically significant,
6. have taken any drugs that lower the immune system.
7. topical immunomodulators
15. Subjects who have used any of the following treatments within 2 weeks prior to
screening/baseline or during the study:
1. topical steroids,
2. topical retinoids,
3. topical acne treatments including over-the-counter preparations
4. topical anti-inflammatory agents
5. topical antibiotics
6. abradants,
7. peels containing glycolic or other acids,
8. washes or soaps, containing glycolic acid,
9. Alpha-hydroxy acids,
10. sulfacetamide sodium,
11. non-mild facial cleansers, moisturizers that contained retinol
12. topical products that contain high amounts of alcohol
13. wax depilation of the face
14. Use of tanning booths
15. The application of alcohol-based toners or any product with high concentrations
of alcohol, astringents, medicated topical preparations (prescription and OTC
products including those with spices or lime ingredients). or medicated make-up,
medicated or harsh soaps, medicated cleansers, and cosmetics that make subject
skin dry to the face (products that have a strong drying effect, particularly
preparations containing sulfur, resorcinol, or salicylic acid with tretinoin or
other retinoids).
16. Subjects who have on-going malignancies requiring systemic treatment or who have any
malignancy of the skin of the facial area.
17. Subjects with active facial sunburn or peeling from sunburn.
18. Subjects who engage in activities that involve excessive or prolonged exposure to
sunlight or weather extremes, such as wind or cold. Exposure to excessive UV radiation
within 1 week prior to screening/baseline.
19. Subjects who use a sauna within 48 hours prior to screening/baseline.
20. Subjects who have unstable medical disorders that are clinically significant or have
life threatening diseases, or other medical condition (i.e., chronic infectious
disease, system disorder, organ disorder, cardiovascular, gastrointestinal,
hematological, hepatic, neurological, pancreatic, renal disease, severe psychiatric
condition, etc.) that, in the Investigator's opinion, would place the study Subject at
undue risk by participation or could jeopardize the integrity of the study
evaluations.
21. Subjects who consume excessive amounts of alcohol (greater than two drinks per day) or
use drugs of abuse (including, but not limited to, cannabinoids, cocaine and
barbiturates) within one year prior to screening.
22. Subjects, who in the opinion of the Investigator, would be non-compliant with the
requirements of the study protocol.
23. Subjects who are unable or unwilling to give informed consent.
24. Subjects who are illiterate.
25. Subjects who have participated in an investigational drug study (i.e., Subjects have
been treated with an investigational drug) within 30 days prior to screening/baseline
or where sufficient washout period has not been achieved; whichever time period is
longer. Subjects who are participating in non-treatment studies such as observational
studies or registry studies can be considered for inclusion.
26. Subjects who have been previously enrolled in this study.
27. Subjects who live in the same household with subjects who are participating or have
been previously enrolled in this study.
28. The subject is a member of the investigational study staff or a family member of the
investigational study staff.
29. Subject having symptoms* of Coronavirus Disease 2019 (COVID-19) within the 10 days
prior to screening/baseline/visit 1 or have had close contact with someone with
suspected or confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
infection within 10 days prior to screening/baseline/visit 1 or who are at high risk
of SARS-CoV-2 infection, defined as adults whose locations or circumstances put them
at appreciable risk of acquiring SARS-CoV-2 infections.
- Stuffy or runny nose, sore throat, shortness of breath (difficulty breathing),
cough, low energy or tiredness, muscle or body aches, headache, chills or
shivering, feeling hot or feverish, vomiting, diarrhea, loss of sense of taste
and smell.
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