Efficacy and Safety Study With Visonac Photodynamic Therapy (PDT)

Double blinded, prospective, randomized, stratified, placebo-controlled, multi-center study in patients with moderate to severe acne vulgaris. Patients with facial severity grades 3 to 4 on the Investigator's Global Assessment (IGA) scale will be included. Each patient will be classified according to age in the two age groups 9 to 12 years and 13 to 35 years and randomized to either Visonac or vehicle cream within each age group. All patients will receive 4 treatments 2 weeks apart (at week 0, 2 ,4 and 6 week). Efficacy evaluation will be done after each treatment and at 12 weeks after the first treatment. Safety evaluations will be performed at each treatment visit and at 12 weeks after the first treatment.

Photographs of patients will be taken before and after treatment at first and last treatment visit, and at 12 weeks after first treatment.

Blood samples will be drawn at 3 visits; pre-treatment visit, one week after first treatment and at one week after last treatment visit.

• Visonac PDT (MAL PDT) (Drug), also known as Visonac, MAL PDT, red light: Cream application followed by illumination with red light.
• Vehicle cream (placebo) (Drug), also known as Vehicle cream, MAL PDT, red light: Cream application followed by illumination with red light.
• PDT (Procedure), also known as Red light: Photodynamic Therapy - Light dose 37 J/cm2

Primary outcomes

• Proportion of Patients With Success According to the Dichotomized IGA Scale Based on Facial Assessments 12 Weeks After the First Treatment. Success is Defined as an Improvement of at Least 2 Grades From the Baseline Score. [12 weeks after the first treatment]
• Absolute Change From Baseline in Facial Inflammatory Lesion Count (Nodules, Papules, and Pustules) [12 weeks after the first treatment]
• Absolute Change From Baseline in Facial Non Inflammatory Lesion Count [12 weeks after first treatment]

Secondary outcomes

• Percent Change From Baseline in Facial Inflammatory (Nodules, Papules, and Pustules)Lesion Count [6 weeks after the first treatment]
• Percent Change From Baseline in Facial Inflammatory (Nodules, Papules, and Pustules)Lesion Count [12 weeks after the first treatment]
• Percent Change From Baseline in Facial Non Inflammatory Lesion Count [6 weeks after first treatment]
• Percent Change From Baseline in Facial Non Inflammatory Lesion Count [12 weeks after first treatment]
• Percent Change From Baseline in Facial Total Lesion Count [6 weeks after the first treatment]
• Percent Change From Baseline in Facial Total Lesion Count [12 weeks after the first treatment]
• Proportion of Patients With a Reduction of at Least 50% From Baseline in Facial Non-inflammatory Lesion Count [12 weeks after last treatment]
• Proportion of Patients With a Reduction of at Least 50% From Baseline in Facial Inflammatory Lesion Count From Baseline [12 weeks after first treatment]
• Absolute Change From Baseline in Facial Inflammatory Lesion Count [6 weeks after the first treatment]
• Absolute Change From Baseline in Facial Non- Inflammatory Lesion Count [6 weeks after the first treatment]
• Absolute Change From Baseline in Facial Total Lesion Count [6 weeks after the first treatment]
• Proportion of Patients With Success According to the Dichotomized IGA Scale Based on Facial Assessments 12 Weeks After the First Treatment. Success is Defined as an Improvement of at Least 2 Grades From the Baseline Score. [6 weeks after the first treatment]
• Facial Pain Assessed Using a Visual Analogue Scale From 0 to 10, Where 0 Indicates no Pain and 10 Indicates Worst Pain Imaginable [directly after first treatment]: Facial pain was assessed on a visual analogue scale ranging from 0-10cm.
• Facial Pain Assessed Using a Visual Analogue Scale From 0 to 10, Where 0 Indicates no Pain and 10 Indicates Worst Pain Imaginable [directly after second treatment]: Facial pain was assessed on a visual analogue scale ranging from 0-10cm.
• Facial Pain Assessed Using a Visual Analogue Scale From 0 to 10, Where 0 Indicates no Pain and 10 Indicates Worst Pain Imaginable [directly after third treatment]: Facial pain was assessed on a visual analogue scale ranging from 0-10cm.
• Facial Pain Assessed Using a Visual Analogue Scale From 0 to 10, Where 0 Indicates no Pain and 10 Indicates Worst Pain Imaginable [directly after fourth treatment]: Facial pain was assessed on a visual analogue scale ranging from 0-10cm.
• Proportion of Patients With Mild and Moderate Hyperpigmentation [at 12 weeks after first treatment]
• Proportion of Patients With Severe Hyperpigmentation [at 12 weeks after first treatment]
• Proportion of Patients With Mild or Moderate Scarring at End of Study [week 12]
• Proportion of Patients With Clear or Almost Clear Scarring at End of Study [week 12]
• Proportion of Patients With Severe and Very Severe Scarring at End of Study [week 12]
• Proportion of Patients With Hypopigmentation (Mild Moderate, Severe) [at 12 weeks after first treatment]
• Proportion of Patients With Dryness (Mild) [at 12 weeks after first treatment]

Sex: All, ages: 9 Years to 35 Years

Inclusion Criteria:

* Female and male patients, above 9 years of age with moderate to severe facial acne vulgaris (IGA score 3-4).
* 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 6 months and must agree to stay with the same product and dose for an additional 6 months.
* Fitzpatrick skin type I through VI.
* Patients with 20 to 100 inflammatory lesions (papules, pustules, and nodules) on the face.
* Patients with 30 to 120 non-inflammatory lesions (open and closed comedones) on the face.
* Patients with no more than 2 nodular lesions on the face.
* Signed and verified informed consent form. For subjects under age of 18, an assent form in conjunction with an informed consent form, signed and verified by parent/guardian.

Exclusion Criteria:

Patients presenting with any of the following will not be included in the study:

* 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 protocol.
* 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 using oral contraceptives, that have not used the same product or dose within the last 6 months and do not agree to stay with the same product and dose for the duration of the study.
* Pregnancy
* Patients undergoing testosterone or any other systemic hormonal treatment.
* Patients using hormonal contraceptives solely for the control of acne.
* Known allergy to MAL, to a similar PDT compound, or to excipients of the cream.
* Patients with porphyria.
* Patients with cutaneous photosensitivity.
* Participation in other clinical studies either concurrently or within the last 30 days, before T1.
* Patients with a washout period for topical treatments e.g., topical BPOs, retinoids and antibiotics, for their acne of less than 14 days, before T1. Medicated cleansers may be used during the washout period and stopped before the treatment.
* Patients with a washout period for oral antibiotics for treatment of their acne of less than 1 month, before T1.
* Patients with a washout period for oral isotretinoin of less than 6 months, before T1.
* Patients with a beard or other facial hair 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.

Participant flow

Outcome results

• Proportion of Patients With Success According to the Dichotomized IGA Scale Based on Facial Assessments 12 Weeks After the First Treatment. Success is Defined as an Improvement of at Least 2 Grades From the Baseline Score. (Primary), Number, percentage of participants: Visonac Cream With PDT 9.26 (1.53 to 16.99); Vehicle Cream With PDT 1.89 (0.00 to 5.55) (p 0.0703)
• Percent Change From Baseline in Facial Inflammatory (Nodules, Papules, and Pustules)Lesion Count (Secondary), Mean, percent change from baseline: Visonac Cream With PDT -35.4 +/- 30.85; Vehicle Cream With PDT -20.3 +/- 38.72
• Absolute Change From Baseline in Facial Inflammatory Lesion Count (Nodules, Papules, and Pustules) (Primary), Mean, lesions: Visonac Cream With PDT -14.0 +/- 17.94; Vehicle Cream With PDT -13.8 +/- 23.76 (p 0.2969)
• Absolute Change From Baseline in Facial Non Inflammatory Lesion Count (Primary), Mean, lesions: Visonac Cream With PDT -14.3 +/- 26.54; Vehicle Cream With PDT -17.1 +/- 25.84 (p 0.8913)
• Percent Change From Baseline in Facial Inflammatory (Nodules, Papules, and Pustules)Lesion Count (Secondary), Mean, Percent change from baseline: Visonac Cream With PDT -33.1 +/- 39.34; Vehicle Cream With PDT -27.5 +/- 44.38
• Percent Change From Baseline in Facial Non Inflammatory Lesion Count (Secondary), Mean, percentage change from baseline: Visonac Cream With PDT -25.3 +/- 39.72; Vehicle Cream With PDT -15.8 +/- 47.11
• Percent Change From Baseline in Facial Non Inflammatory Lesion Count (Secondary), Mean, percentage change from baseline: Visonac Cream With PDT -26.0 +/- 52.23; Vehicle Cream With PDT -24.4 +/- 37.66
• Percent Change From Baseline in Facial Total Lesion Count (Secondary), Mean, Percent change from baseline: Visonac Cream With PDT -29.5 +/- 27.72; Vehicle Cream With PDT -18.0 +/- 35.39
• Percent Change From Baseline in Facial Total Lesion Count (Secondary), Mean, Percent change from baseline: Visonac Cream With PDT -29.8 +/- 36.04; Vehicle Cream With PDT -26.8 +/- 29.61
• Proportion of Patients With a Reduction of at Least 50% From Baseline in Facial Non-inflammatory Lesion Count (Secondary), Number, participants: Visonac Cream With PDT 17; Vehicle Cream With PDT 10
• Proportion of Patients With a Reduction of at Least 50% From Baseline in Facial Inflammatory Lesion Count From Baseline (Secondary), Number, participants: Visonac Cream With PDT 20; Vehicle Cream With PDT 19
• Absolute Change From Baseline in Facial Inflammatory Lesion Count (Secondary), Mean, lesions: Visonac Cream With PDT -17.5 +/- 9.0; Vehicle Cream With PDT -10.8 +/- 22.41
• Absolute Change From Baseline in Facial Non- Inflammatory Lesion Count (Secondary), Mean, lesions: Visonac Cream With PDT 12.9 +/- 21.41; Vehicle Cream With PDT 11.3 +/- 28.24
• Absolute Change From Baseline in Facial Total Lesion Count (Secondary), Mean, lesions: Visonac Cream With PDT -27.2 +/- 26.19; Vehicle Cream With PDT -20.6 +/- 36.68
• Proportion of Patients With Success According to the Dichotomized IGA Scale Based on Facial Assessments 12 Weeks After the First Treatment. Success is Defined as an Improvement of at Least 2 Grades From the Baseline Score. (Secondary), Number, Participants: Visonac Cream With PDT 3; Vehicle Cream With PDT 1
• Facial Pain Assessed Using a Visual Analogue Scale From 0 to 10, Where 0 Indicates no Pain and 10 Indicates Worst Pain Imaginable (Secondary), Mean, cm: Visonac Cream With PDT 1.5 (0.0 to 9.8); Vehicle Cream With PDT 0.28 (0.0 to 3.6)
• Facial Pain Assessed Using a Visual Analogue Scale From 0 to 10, Where 0 Indicates no Pain and 10 Indicates Worst Pain Imaginable (Secondary), Mean, cm: Visonac Cream With PDT 1.37 (0.0 to 8.5); Vehicle Cream With PDT 0.15 (0.0 to 1.6)
• Facial Pain Assessed Using a Visual Analogue Scale From 0 to 10, Where 0 Indicates no Pain and 10 Indicates Worst Pain Imaginable (Secondary), Mean, cm: Visonac Cream With PDT 1.53 (0.0 to 8.1); Vehicle Cream With PDT 0.17 (0.0 to 1.4)
• Facial Pain Assessed Using a Visual Analogue Scale From 0 to 10, Where 0 Indicates no Pain and 10 Indicates Worst Pain Imaginable (Secondary), Mean, cm: Visonac Cream With PDT 1.39 (0.0 to 8.2); Vehicle Cream With PDT 0.19 (0.0 to 2.6)
• Proportion of Patients With Mild and Moderate Hyperpigmentation (Secondary), Number, participants: Visonac Cream With PDT 26; Vehicle Cream With PDT 32
• 6 more outcome measures not shown.

Adverse events

Other adverse events by term

• Lawrence F. Eichenfield, M.D, Principal investigator, Children's Specialists of San Diego / Rady Children's Hospital San Diego