Photodynamic Therapy (PDT) With Methyl Aminolevulinate (MAL) Cream in Moderate to Severe Acne

Study Overview
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Brief Summary
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This multicenter study will be divided into 2 phases. The first phase will be an open label, dose-escalation phase, while the second will be a blinded, randomized, vehicle-controlled, parallel-group, dose-response phase. The second phase will only start if the first phase succeeds in establishing well tolerated dose(s). Patients with moderate to severe acne vulgaris in the face will be included.The results from part 2 has been presented in the result section.

Detailed Description
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For the second part: All patients will receive 4 PDT sessions 2 weeks apart using a light dose of 37 J/cm2. One treatment group will receive vehicle cream, while the other 2 groups will receive MAL cream with a concentration of 40 mg/g and 80 mg/g, respectively. The MAL and vehicle cream will be applied in a thin layer on clean skin and left for 1.5 hours under occlusion before illumination.

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Methyl aminolevulinate (MAL) PDT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male patients, age 15 to 40 years with moderate to severe facial acne vulgaris (IGA score 3-4). Patients with skin type I to IV (Fitzpatrick). Patients with 20 to 100 inflammatory lesions (papules, pustules, and nodules) on the face excluding lesions on the nose and in the peri-ocular area. Patients with up to 200 noninflammatory lesions (open and closed comedones) on the face. Patients with no more than 2 nodular lesions on the face. Patients who are surgically sterile, 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 Day 0. 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. Patients must be willing and capable of following study instructions to the extent and degree required by the protocol. Patients must sign the approved informed consent form prior to any study procedures. Patients must be willing to be photographed. Patients must be willing to sign a photography consent form. Exclusion Criteria: Known allergy to MAL, to a similar PDT compound, or to excipients of the cream. Participation in other clinical studies either concurrently or within the last 30 days. Patients who have a condition or who are in a situation, which, in the investigator's opinion, may put the patient at risk, may confound the study results, or may interfere with the patient's participation in the study. Clinically significant sensitivity to visible light, or has porphyria or porphyrin sensitivity. Exposure to ultraviolet radiation (UVB phototherapy, sun tanning salons) within the last 30 days. Patients with a washout period for topical treatments for their acne of less than 14 days. 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. Patients with a washout period for oral isotretinoin of less than 6 months. Patients with a beard or other facial hair that might interfere with study assessments.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>PDT using MAL concentration A | Drug: Methyl aminolevulinate (MAL) PDT<br>* Cream application followed by illumination with red light<br>|
| Experimental: 2<br>PDT using MAL concentration B | Drug: Methyl aminolevulinate (MAL) PDT<br>* Cream application followed by illumination with red light<br>|
| Placebo Comparator: 3<br>PDT using Placebo cream | Drug: Methyl aminolevulinate (MAL) PDT<br>* Cream application followed by illumination with red light<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Success, Defined as Improvement of at Least 2 Grades From Baseline According to the IGA Scale Based on Facial Assessment |  | 12 weeks after last treatment | 
| Change in Facial Inflammatory (Nodules, Papules, and Pustules) Lesion Counts |  | 12 weeks after last treatment | 
| Change in Facial Inflammatory (Nodules, Papules, and Pustules) Lesion Counts From Baseline |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Percentage Change in Facial Inflammatory (Nodules, Papules, and Pustules) Lesion Counts From Baseline |  | 3 weeks after last treatment | 
| Median Percentage Change in Facial Inflammatory (Nodules, Papules, and Pustules) Lesion Counts From Baseline |  | 6 weeks after last treatment | 
| Median Percentage Change in Facial Non Inflammatory Lesion Counts From Baseline |  | 6 weeks after last treatment | 
| Percent Reduction in Total Lesion Counts From Baseline |  | 6 weeks after last treatment | 
| Proportion of Success, Defined as Improvement of at Least 2 Grades From Baseline According to the IGA Scale Based on Facial Assessment |  | 6 weeks after last treatment | 
| The Proportion of Patients Rated as Clear or Almost Clear at 12 Weeks After Last Treatment |  | 12 weeks after last treatment | 
| Facial Pain Using Visual Analouge Scale From 0 to 10, Were 0 Indicates no Pain and 10 Indicates Worst Pain. | Measure was assessed on a Visual Analogue Scale from 0 to 10 cm | immediately after illumination-first treatment | 
| Facial Pain Using Visual Analouge Scale From 0 to 10, Were 0 Indicates no Pain and 10 Indicates Worst Pain | Measure was assessed on a Visual Analogue Scale from 0 to 10 cm | immediately after second treatment | 
| Facial Pain Using Visual Analouge Scale From 0 to 10, Were 0 Indicates no Pain and 10 Indicates Worst Pain. | Measure was assessed on a Visual Analogue Scale from 0 to 10 cm | immediately after third treatment | 
| Facial Pain Using Visual Analouge Scale From 0 to 10, Were 0 Indicates no Pain and 10 Indicates Worst Pain. | Measure was assessed on a Visual Analogue Scale from 0 to 10 cm | immediately after illumination-fourth treatment treatment | 
| Proportion of Patients With Mild and Moderate Erythema After First Treatment |  | immediately after first treatment | 
| Proportion of Patients With Mild and Moderate Erythema After First Treatment |  | 2 days after first treatment | 
| Proportion of Patients With Mild and Moderate Erythema After Second Treatment |  | immediately after second treatment | 
| Proportion of Patients With Mild and Moderate Erythema After Third Treatment |  | immediately after third treatment | 
| Proportion of Patients With Mild and Moderate Erythema After Fourth Treatment |  | immediately after fourth treatment | 
| Proportion of Patients With Severe Erythema After First Treatment |  | immediately after first treatment | 
| Proportion of Patients With Severe Erythema 2 Days After First Treatment |  | 2 days after first treatment | 
| Proportion of Patients With Severe Erythema 7 Days After First Treatment |  | 7 days after first treatment | 
| Proportion of Patients With Severe Erythema After Second Treatment |  | immediately after second treatment | 
| Proportion of Patients With Severe Erythema After Third Treatment |  | immediately after third treatment | 
| Proportion of Patients With Severe Erythema After Fourth Treatment |  | immediately after fourth treatment | 
| Proportion of Patients With Mild and Moderate Hyperpigmentation After First Treatment |  | 2 days after treatment | 
| Proportion of Patients With Mild and Moderate Hyperpigmentation After First Treatment |  | 2 weeks after first treatment | 
| Proportion of Patients With Mild and Moderate Hyperpigmentation After Last Treatment |  | 2 weeks after last treatment | 
| Proportion of Patients With Mild and Moderate Hyperpigmentation After Last Treatment |  | 6 weeks after last treatment | 
| Proportion of Patients With Mild and Moderate Hyperpigmentation After Last Treatment |  | 12 weeks after last treatment | 
| Proportion of Patients With Mild and Moderate Hypopigmentation After First Treatment |  | 2 days after first treatment | 
| Proportion of Patients With Mild and Moderate Hypopigmentation After Last Treatment |  | 2 weeks after last treatment | 
| Proportion of Patients With Mild and Moderate Hypopigmentation After First Treatment |  | 2 weeks after first treatment | 
| Proportion of Patients With Mild and Moderate Hypopigmentation After Last Treatment |  | 6 weeks after last treatment | 
| Proportion of Patients With Mild and Moderate Hypopigmentation After Last Treatment |  | 12 weeks after last treatment |