Acne Vulgaris
Conditions
Keywords
Acne vulgaris, PDT
Brief summary
This study is intended to evaluate the efficacy and safety of Visonac Photodynamic Therapy (PDT) in patients with severe acne, score 4 on global IGA scale. The null hypothesis is that Visonac PDT is equal to vehicle PDT against the alternative hypothesis that Visonac PDT is different compared to vehicle PDT at week 12.
Interventions
DRUGVisonac PDT
cream application prior to illumination with red light
DRUGVehicle cream with PDT
placebo/vehicle cream application prior to illumination with red light
Sponsors
Photocure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Female and male patients, from 12-35 years of age with severe facial acne vulgaris (IGA score 4 on IGA scale) * Signed and verified informed consent form and photo consent form. For subjects under age of 18, an assent form in conjunction with an informed consent form, signed and verified by parent/guardian. * Female patients who are surgically sterile, pre-menstrual, postmenopausal, abstinent, or willing to use an adequate means of contraception including birth control pills, or barrier methods and spermicide for at least 14 days prior to T1. Patients using birth control pills must have used the same product and dose for at least 3 months and must agree to stay with the same product and dose for an additional 3 months. * Fitzpatrick skin type I through VI, * Patients with 25 to 75 inflammatory lesions (papules, pustules, and nodules) on the face. * Patients with 20 to 100 non-inflammatory lesions (open and closed comedones) on the face.
Exclusion criteria
* Patients with acne conglobata, acne fulminans, secondary acne (chloracne, drug-induced acne, etc.) * Patients with more than 3 nodules on the face. * Patient is the investigator or any sub investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study. * Patients unlikely to comply with the protocol, e.g. mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the clinical study, uncooperative attitude or unlikelihood of completing the study (e.g. drug or alcohol abuse). * Female patients with childbearing potential (i.e. ovulation, pre-menopausal, not surgically sterilized) and sexually active, not willing to use a medically accepted contraceptive regimen (as described under inclusion criteria) while on treatment. * Pregnancy. * Nursing. * Participation in other clinical studies either currently or within the last 30 days. * Patients with porphyria. * Patients with cutaneous photosensitivity. * Known allergy to MAL, to a similar PDT compound, or to excipients of the cream * Patients using testosterone, any other systemic hormonal treatment or hormonal contraceptives solely for control of acne. * Patients who have received topical treatments for their facial acne within the last 14 days (e.g steroids, retinoids, glycolic acid, benzoyl peroxide, anti inflammatory agents, antibiotics). Medicated cleansers may be used during the washout period and stopped before the treatment. * Patients who have received oral antibiotics for treatment of their acne within the last month. * Patients who have received oral isotretinoin within the last 6 months. * Patient who have received facial procedures like dermabrasion, chemical or laser peels within the last 1 month. * Patients using testosterone, any systemic hormonal treatment for other reasons than acne treatment and has not been on the same product and dose for at least 3 months * Patients with moderate, severe or very severe facial acne scarring according to scarring scale described in section 10.4.3. * Patients with a beard that might interfere with study assessments. * Patients with melanoma or dysplastic nevi in the treatment area. * Exposure to ultraviolet radiation (UVB phototherapy, sun tanning salons) within the last 30 days * Exposure to PDT within 12 weeks before T1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute Change From Baseline in Facial Inflammatory Lesion Count (Nodules, Papules, and Pustules). | From baseline to 12 weeks after first treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Facial Inflammatory (Nodules, Papules, and Pustules)Lesion Counts. | From baseline to 12 weeks after the first treatment | — |
| Proportion of Patients With Success According to IGA Scale Based on the Facial Assessment. | From baseline to 12 weeks after first treatment | One Investigator Global Assessment (IGA) scale was used including inflammatory and non-inflammatory lesions. The investigator qualitatively graded the overall acne severity on a scale from 0 to 4, with 4 being the most severe. Success was defined as an improvement of at least 2 grades from the baseline score. |
| Pain During Illumination. | Immediately after first treatment | Pain during illumination was assessed by patient using a Visual Analogue Scale (VAS) from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain imaginable. |
| Number of Patients With Adverse Events. | From administration of investigational medicinal product (IMP) until 12 weeks after first IMP administration | — |
| Erythema Score of Mild and Moderate | Immediately after first treatment | Clinical assessment using a 4 point scale; none, mild, moderate, severe |
| Absolute Change From Baseline in Facial Non-inflammatory Lesion Count (Open and Closed Comedones) | From baseline to 12 weeks after the first treatment | — |
| Percent Change From Baseline in Facial Non-inflammatory Lesion Count (Open and Closed Comedones) | From baseline to 12 weeks after first treatment | — |
| Erythema Score of Severe | Immediately after first treatment | Clinical assessment using a 4 point scale; none, mild, moderate, severe |
| Mild and Moderate Scarring According to Scarring Score | at week 12 after first treatment | Clinical assessment using a 6 point scale; Clear, Almost clear, Mild, Moderate, Severe and Very severe |
| Severe and Very Severe Scarring According to Scarring Score | at week 12 after first treatment | Clinical assessment using a 6 point scale; Clear, Almost clear, Mild, Moderate, Severe and Very severe |
| Clear and Almost Clear Scarring According to Scarring Score | at week 12 after first treatment | Clinical assessment using a 6 point scale; Clear, Almost clear, Mild, Moderate, Severe and Very severe |
Countries
United States
Participant flow
Recruitment details
Dermatology clinics in the US.
Participants by arm
| Arm | Count |
|---|---|
| Vehicle Cream With PDT Placebo treatment, Light dose 37 J/cm2
Visonac PDT : cream application prior to illumination with red light | 53 |
| Visonac Cream With PDT active treatment with light dose of 37J/cm2
Visonac PDT : cream application prior to illumination with red light | 100 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 12 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other | 2 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Vehicle Cream With PDT | Visonac Cream With PDT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 35 Participants | 59 Participants | 94 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 41 Participants | 59 Participants |
| Age, Continuous | 18.6 years STANDARD_DEVIATION 5.8 | 18.6 years STANDARD_DEVIATION 5.5 | 18.6 years STANDARD_DEVIATION 5.6 |
| Region of Enrollment United States | 53 participants | 100 participants | 153 participants |
| Sex: Female, Male Female | 22 Participants | 44 Participants | 66 Participants |
| Sex: Female, Male Male | 31 Participants | 56 Participants | 87 Participants |
| Skin type Skin type I | 0 participants | 1 participants | 1 participants |
| Skin type Skin type II | 24 participants | 34 participants | 58 participants |
| Skin type Skin type III | 15 participants | 38 participants | 53 participants |
| Skin type Skin type IV | 7 participants | 15 participants | 22 participants |
| Skin type Skin type V | 6 participants | 8 participants | 14 participants |
| Skin type Skin type VI | 1 participants | 4 participants | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 53 | 48 / 100 |
| serious Total, serious adverse events | 0 / 53 | 0 / 100 |
Outcome results
Primary
Absolute Change From Baseline in Facial Inflammatory Lesion Count (Nodules, Papules, and Pustules).
Time frame: From baseline to 12 weeks after first treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Cream With PDT | Absolute Change From Baseline in Facial Inflammatory Lesion Count (Nodules, Papules, and Pustules). | -7.8 lesion count | Standard Deviation 21.4 |
| Visonac Cream With PDT | Absolute Change From Baseline in Facial Inflammatory Lesion Count (Nodules, Papules, and Pustules). | -15.6 lesion count | Standard Deviation 16.4 |
p-value: 0.00695% CI: [-12.5, -2.2]ANCOVA
Secondary
Absolute Change From Baseline in Facial Non-inflammatory Lesion Count (Open and Closed Comedones)
Time frame: From baseline to 12 weeks after the first treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Cream With PDT | Absolute Change From Baseline in Facial Non-inflammatory Lesion Count (Open and Closed Comedones) | -10.7 lesion count | Standard Deviation 22.1 |
| Visonac Cream With PDT | Absolute Change From Baseline in Facial Non-inflammatory Lesion Count (Open and Closed Comedones) | -11.8 lesion count | Standard Deviation 19 |
p-value: 0.852795% CI: [-6.6, 5.5]ANCOVA
Secondary
Clear and Almost Clear Scarring According to Scarring Score
Clinical assessment using a 6 point scale; Clear, Almost clear, Mild, Moderate, Severe and Very severe
Time frame: at week 12 after first treatment
Population: 100 patients were included and 83 patients completed the study in the Visonac treatment arm. However, a few patients came back for the week 12 visit only, and have data for scarring. The total number of patients with scarring data at 12 weeks in this group is 91.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Clear and Almost Clear Scarring According to Scarring Score | 25 participants |
| Visonac Cream With PDT | Clear and Almost Clear Scarring According to Scarring Score | 53 participants |
Secondary
Erythema Score of Mild and Moderate
Clinical assessment using a 4 point scale; none, mild, moderate, severe
Time frame: 2 days after first treatment
Population: Of the 100 patients who were included in the Visonac treatment arm, 5 dropped out prior to the day 2 erythema assessment. The number of patients with erythema data at this assessment point is 95.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Erythema Score of Mild and Moderate | 26 participants |
| Visonac Cream With PDT | Erythema Score of Mild and Moderate | 65 participants |
Secondary
Erythema Score of Mild and Moderate
Clinical assessment using a 4 point scale; none, mild, moderate, severe
Time frame: Immediately after first treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Erythema Score of Mild and Moderate | 37 participants |
| Visonac Cream With PDT | Erythema Score of Mild and Moderate | 86 participants |
Secondary
Erythema Score of Severe
Clinical assessment using a 4 point scale; none, mild, moderate, severe
Time frame: Immediately after first treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Erythema Score of Severe | 0 participants |
| Visonac Cream With PDT | Erythema Score of Severe | 3 participants |
Secondary
Erythema Score of Severe
Clinical assessment using a 4 point scale; none, mild, moderate, severe
Time frame: 2 days after first treatment
Population: Of the 100 patients who were included in the Visonac treatment arm, 5 dropped out prior to the day 2 erythema assessment. The number of patients with erythema data at this assessment point is 95.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Erythema Score of Severe | 0 participants |
| Visonac Cream With PDT | Erythema Score of Severe | 0 participants |
Secondary
Mild and Moderate Scarring According to Scarring Score
Clinical assessment using a 6 point scale; Clear, Almost clear, Mild, Moderate, Severe and Very severe
Time frame: at week 12 after first treatment
Population: 100 patients were included and 83 patients completed the study in the Visonac treatment arm. However, a few patients came back for the week 12 visit only, and have data for scarring. The total number of patients with scarring data at 12 weeks in this group is 91.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Mild and Moderate Scarring According to Scarring Score | 21 participants |
| Visonac Cream With PDT | Mild and Moderate Scarring According to Scarring Score | 38 participants |
Secondary
Number of Patients With Adverse Events.
Time frame: From administration of investigational medicinal product (IMP) until 12 weeks after first IMP administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Number of Patients With Adverse Events. | 14 participants |
| Visonac Cream With PDT | Number of Patients With Adverse Events. | 48 participants |
Secondary
Pain During Illumination.
Pain during illumination was assessed by patient using a Visual Analogue Scale (VAS) from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain imaginable.
Time frame: Immediately after first treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vehicle Cream With PDT | Pain During Illumination. | 0.52 VAS score in cm |
| Visonac Cream With PDT | Pain During Illumination. | 3.38 VAS score in cm |
Secondary
Percent Change From Baseline in Facial Inflammatory (Nodules, Papules, and Pustules)Lesion Counts.
Time frame: From baseline to 12 weeks after the first treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vehicle Cream With PDT | Percent Change From Baseline in Facial Inflammatory (Nodules, Papules, and Pustules)Lesion Counts. | -26.6 percent change |
| Visonac Cream With PDT | Percent Change From Baseline in Facial Inflammatory (Nodules, Papules, and Pustules)Lesion Counts. | -43.8 percent change |
p-value: 0.003295% CI: [-33.2, -6.8]ANCOVA
Secondary
Percent Change From Baseline in Facial Non-inflammatory Lesion Count (Open and Closed Comedones)
Time frame: From baseline to 12 weeks after first treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vehicle Cream With PDT | Percent Change From Baseline in Facial Non-inflammatory Lesion Count (Open and Closed Comedones) | -37.0 percent change |
| Visonac Cream With PDT | Percent Change From Baseline in Facial Non-inflammatory Lesion Count (Open and Closed Comedones) | -31.0 percent change |
p-value: 0.716195% CI: [-16.5, 11.3]ANCOVA
Secondary
Proportion of Patients With Success According to IGA Scale Based on the Facial Assessment.
One Investigator Global Assessment (IGA) scale was used including inflammatory and non-inflammatory lesions. The investigator qualitatively graded the overall acne severity on a scale from 0 to 4, with 4 being the most severe. Success was defined as an improvement of at least 2 grades from the baseline score.
Time frame: From baseline to 12 weeks after first treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Proportion of Patients With Success According to IGA Scale Based on the Facial Assessment. | 14 participants |
| Visonac Cream With PDT | Proportion of Patients With Success According to IGA Scale Based on the Facial Assessment. | 44 participants |
p-value: 0.0125Regression, Logistic
Secondary
Severe and Very Severe Scarring According to Scarring Score
Clinical assessment using a 6 point scale; Clear, Almost clear, Mild, Moderate, Severe and Very severe
Time frame: at week 12 after first treatment
Population: 100 patients were included and 83 patients completed the study in the Visonac treatment arm. However, a few patients came back for the week 12 visit only, and have data for scarring. The total number of patients with scarring data at 12 weeks in this group is 91.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle Cream With PDT | Severe and Very Severe Scarring According to Scarring Score | 0 participants |
| Visonac Cream With PDT | Severe and Very Severe Scarring According to Scarring Score | 0 participants |