Clinical trial NCT00706433: Light Dose Ranging Study of Photodynamic Therapy (PDT) With Levulan + Blue Light Versus Vehicle + Blue Light in Severe Facial Acne
Official title: A Randomized, Evaluator-blinded, Parallel Group Light Dose Ranging Study of Photodynamic Therapy With Levulan Topical Solution + Blue Light Versus Levulan Topical Solution Vehicle + Blue Light on Moderate to Severe Facial Acne Vulgaris
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acne Vulgaris
Keywords: Photodynamic Therapy
Lead sponsor: DUSA Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-06-27
Enrollment: 266
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine and compare the safety and efficacy of multiple broad area photodynamic therapy treatments with aminolevulinic acid (ALA-PDT) and vehicle (VEH-PDT) in subjects with moderate to severe facial acne vulgaris.

Detailed description: This is a Phase II multicenter, randomized, evaluator-blinded, vehicle-controlled, parallel group light dose ranging study of photodynamic therapy in subjects with moderate to severe facial acne vulgaris.

Subjects will be randomized to one of the following four treatment groups (1:1:1:1) to receive topical Levulan® Kerastick® containing 20% aminolevulinic acid HCL (ALA, active study drug) or the Kerastick® containing vehicle ingredients only (VEH).

* Group 1 will have ALA applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds)
* Group 2 will have ALA applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 500 seconds (8 minutes 20 seconds)
* Group 3 will have VEH applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds)
* Group 4 will have VEH applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 500 seconds (8 minutes 20 seconds)

Each subject may receive up to four treatments at three week (± 2 days) intervals. The power density (dose rate) and the total fluence (light dose) used at each treatment is intended to remain constant throughout each subject's participation. If a subject meets or exceeds the criteria restricting retreatment (CRR) prior to retreatment (Section 5.6), he/she will not receive additional PDT treatment at that visit and will be asked to return for the next scheduled PDT visit 3 weeks later, if applicable.

Post-treatment follow-up visits will be scheduled to occur at 3 and 6 weeks after the subject's final PDT.

Grading of the subject's facial acne will be conducted by a blinded evaluator who will remain blinded with respect to the subject's treatment assignment. Tolerability of treatment will be assessed by evaluations of the local skin response (erythema, edema, etc.) and will be conducted by an unblinded evaluator.

Safety will be evaluated by adverse events and local skin responses reported during the study.

Eligibility criteria: Inclusion Criteria:

* Subject is male or non-pregnant female 12 years of age or older.
* Females must be post-menopausal, surgically sterile or using a medically acceptable form of birth control, with a negative urine pregnancy test at the Baseline visit.
* Subject has provided written and verbal informed consent. A subject under 18 years of age must be accompanied by the parent or legal guardian at the time of assent/consent signing. The parent or legal guardian must also provide informed consent for the subject.
* Subject has moderate to severe facial acne vulgaris (including the nose), with at least 20 inflammatory lesions (papules, pustules, nodules).
* Subject has moderate to severe acne as defined by an Investigator Global Assessment of 3 or 4 \[0 (clear) to 4 (severe) scale\].
* Subject has a history of recurrent herpes simplex labialis infection in the treatment area AND has had an outbreak within the last 12 months must be placed on antiviral prophylaxis as specified in the protocol.
* Subject is willing to comply with study instructions and return to the clinic for required visits.
* Subject must have used the same type and brand of make-up, other facial products and hair products (e.g. shampoo, gel, hair spray, mousse, etc.) for at least 1 month prior to the Baseline Visit (General Skin \& Hair Care). Upon enrollment, all subjects must a) use exclusively an Investigator approved facial cleanser and b) agree to continue their other General Skin \& Hair Care for the entire study.

Exclusion Criteria:

* Subject is pregnant, lactating, or is planning to become pregnant during the study.
* Subject has a history of cutaneous photosensitization, porphyria, hypersensitivity to porphyrins or photodermatosis.
* Subject has any skin pathology or condition that could interfere with the evaluation of the test product or requires the use of interfering topical or systemic therapy.
* Subject has greater than 4 facial nodules (nodule = lesion greater than or equal 0.5 cm in diameter)
* Subject has an uncorrected coagulation defect or concurrently uses anticoagulants (except aspirin).
* Subject has any condition which, in the investigator's opinion, would make it unsafe for the subject to participate in this research study.
* Subject is currently enrolled in an investigational drug or device study.
* Subject has received an investigational drug or been treated with an investigational device within 30 days prior to the initiation of treatment (baseline).
* Subject has facial hair that could interfere with the study assessments in the opinion of the investigator.
* Subject is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function.
* Subject may be unreliable for the study including subjects who engage in excessive alcohol intake or drug abuse, or subjects who are unable to return for scheduled follow-up visits.
* Subject has a known sensitivity to one or more of the vehicle components (ethyl alcohol, isopropyl alcohol, laureth 4, polyethylene glycol).
* Subject has used photosensitizing drugs, e.g. declomycin, tetracycline, sulfa antibiotics, phenothiazines, etc. within a timeframe where photosensitization from these drugs may still be present.
* Subject has used OTC acne medicated cleansers or soaps within 2 weeks of the initiation of treatment.
* Subject has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the trial.
* Subject has used any of the following topical anti-acne preparations on the face: a.) Topical anti-acne treatments including benzoyl peroxide, antibiotics, azelaic acid, corticosteroids and salicylic acid within 2 weeks of the initiation of treatment b.) Retinoids, including tazarotene, adapalene, tretinoin within 4 weeks of the initiation of treatment. c.) Light treatments, microdermabrasion or chemical peels within 8 weeks of the initiation of treatment.
* Subject has used any of the following systemic anti-acne medications: a.) Corticosteroids (including intramuscular and intralesional injections) within 4 weeks of the initiation of treatment. Inhaled corticosteroids are allowed if use is stable (stable use is defined as dose and frequency unchanged for at least 2 weeks prior to the initiation of treatment). b.) Antibiotics within 4 weeks of the initiation of treatment. c.) Nicotinamide containing products within 4 weeks of the initiation of treatment. d.) Spironolactone within 8 weeks of the initiation of treatment. d.) Retinoid therapy within 6 months of the initiation of treatment.

Primary outcomes:
measure: Change in Inflammatory Lesion Counts Relative to Baseline
timeFrame: Baseline and 3 weeks after final treatment
measure: Investigator Global Assessment of Acne Severity Successes
timeFrame: Baseline and 3 weeks after final treatment
Secondary outcomes:
measure: Percent Change in Inflammatory Lesion Counts Relative to Baseline
timeFrame: Baseline and 3 weeks after final treatment
measure: Percent Change in Inflammatory Lesion Counts Relative to Baseline
timeFrame: Baseline and 6 weeks after final treatment
measure: Subject Satisfaction Score
timeFrame: 6 weeks after final treatment
measure: Change in Inflammatory Lesion Counts Relative to Baseline
timeFrame: Baseline and 6 weeks after final treatment
measure: Investigator Global Assessment of Acne Severity Successes
timeFrame: Baesline and 6 weeks after final treatment
measure: Hyperpigmentation 48 Hours After PDT #1
timeFrame: 48 hours after PDT #1
measure: Hyperpigmentation at Visit 3 (Week 3)
timeFrame: Visit 3 (Week 3)
measure: Hyperpigmentation at Visit 5 (Week 6)
timeFrame: Visit 5 (Week 6)
measure: Hyperpigmentation at Visit 7 (Week 9)
timeFrame: Visit 7 (Week 9)
measure: Hyperpigmentation at Visit 9 (3 Weeks After Final PDT)
timeFrame: Visit 9 (3 weeks after final PDT)
measure: Hyperpigmentation at Visit 10 (6 Weeks After Final PDT)
timeFrame: Visit 10 (6 weeks after final PDT)
measure: Hypopigmentation 48 Hours Post PDT #1
timeFrame: 48 hours post PDT #1
measure: Hypopigmentation at Visit 3 (Week 3)
timeFrame: Visit 3 (Week 3)
measure: Hypopigmentation at Visit 5 (Week 6)
timeFrame: Visit 5 (Week 6)
measure: Hypopigmentation at Visit 7 (Week 9)
timeFrame: Visit 7 (Week 9)
measure: Hypopigmentation at Visit 9 (3 Weeks After Final PDT)
timeFrame: Visit 9 (3 weeks after final PDT)
measure: Hypopigmentation at Visit 10 (6 Weeks After Final PDT)
timeFrame: Visit 10 (6 weeks after final PDT)
measure: Erythema at Baseline (Pre-light)
timeFrame: Baseline (pre-light)
measure: Erythema at Baseline - Post Light Treatment
timeFrame: Baseline - post light treatment
measure: Erythema 48 Hours After PDT #1
timeFrame: 48 hours after PDT #1
measure: Erythema at Visit 3 (Week 3 - Pre Study Drug Application)
timeFrame: Visit 3 (Week 3 - pre study drug application)
measure: Erythema at Visit 3 (Week 3 - Pre-light)
timeFrame: Visit 3 (Week 3 - pre-light)
measure: Erythema at Visit 3 (Week 3 - Post Light Treatment)
timeFrame: Visit 3 (Week 3 - post light treatment)
measure: Erythema at Visit 5 (Week 6 - Prior to Study Drug Application)
timeFrame: Visit 5 (Week 6 - prior to study drug application)
measure: Erythema at Visit 5 (Weeks 6 - Pre-light Treatment)
timeFrame: Visit 5 (Weeks 6 - pre-light treatment)
measure: Erythema at Visit 5 (Week 6 - Post Light Treatment)
timeFrame: Visit 5 (Week 6 - post light treatment)
measure: Erythema at Visit 7 (Week 9 - Prior to Study Drug Application)
timeFrame: Visit 7 (Week 9 - prior to study drug application)
measure: Erythema at Visit 7 (Week 9 - Pre Light Treatment)
timeFrame: Visit 7 (Week 9 - pre light treatment)
measure: Erythema at Visit 7 (Week 9 - Post Light Treatment)
timeFrame: Visit 7 (Week 9 - post light treatment)
measure: Erythema 3 Weeks After Final PDT
timeFrame: 3 Weeks after Final PDT
measure: Erythema 6 Weeks After Final PDT
timeFrame: 6 Weeks after Final PDT
measure: Edema at Baseline - Pre Light Treatment
timeFrame: Baseline - pre light treatment
measure: Edema at Baseline - Post Light Treatment
timeFrame: Baseline - Post Light Treatment
measure: Edema 48 Hours After PDT #1
timeFrame: 48 hours after PDT #1
measure: Edema at Visit 3 (Week 3 - Before Study Drug Application)
timeFrame: Visit 3 (Week 3 - before study drug application)
measure: Edema at Visit 3 (Week 3 - Before Light Treatment)
timeFrame: Visit 3 (Week 3 - before light treatment)
measure: Edema at Visit 3 (Week 3 - Post Light Treatment)
timeFrame: Visit 3 (Week 3 - post light treatment)
measure: Edema at Visit 5 (Week 6 - Before Study Drug Application)
timeFrame: Visit 5 (Week 6 - before study drug application)
measure: Edema at Visit 5 (Week 6 - Pre Light Treatment)
timeFrame: Visit 5 (Week 6 - pre light treatment)
measure: Edema at Visit 5 (Week 6 - Post Light Treatment)
timeFrame: Visit 5 (Week 6 - post light treatment)
measure: Edema at Visit 7 (Week 9 - Before Study Drug Application)
timeFrame: Visit 7 (Week 9 - before study drug application)
measure: Edema at Visit 7 (Week 9 - Prior to Light Treatment)
timeFrame: Visit 7 (Week 9 - prior to light treatment)
measure: Edema at Visit 7 (Week 9 - Post Light Treatment)
timeFrame: Visit 7 (Week 9 - post light treatment)
measure: Edema 3 Weeks After Final PDT
timeFrame: 3 weeks after final PDT
measure: Edema 6 Weeks After Final PDT
timeFrame: 6 weeks after final PDT
measure: Stinging/Burning at Baseline - Before Light Treatment
timeFrame: Baseline - before light treatment
measure: Stinging/Burning at Baseline - During Light
timeFrame: Baseline - during light
measure: Stinging/Burning at Baseline - Post Light Treatment
timeFrame: Baseline - post light treatment
measure: Stinging/Burning 48 Hours Post PDT #1
timeFrame: 48 hours post PDT #1
measure: Stinging/Burning at Visit 3 (Week 3 - Before Study Drug Application)
timeFrame: Visit 3 (Week 3 - before study drug application)
measure: Stinging/Burning at Visit 3 (Week 3 - Before Light Treatment)
timeFrame: Visit 3 (Week 3 - before light treatment)
measure: Stinging/Burning at Visit 3 (Week 3 - During Light Treatment)
timeFrame: Visit 3 (Week 3 - during light treatment)
measure: Stinging/Burning at Visit 3 (Week 3 - Post Light Treatment)
timeFrame: Visit 3 (Week 3 - post light treatment)
measure: Stinging/Burning at Visit 5 (Week 6 - Before Study Drug Application)
timeFrame: Visit 5 (Week 6 - before study drug application)
measure: Stinging/Burning at Visit 5 (Week 6 - Prior to Light Treatment)
timeFrame: Visit 5 (Week 6 - prior to light treatment)
measure: Stinging/Burning at Visit 5 (Week 6 - During Light Treatment)
timeFrame: Visit 5 (Week 6 - during light treatment)
measure: Stinging/Burning at Visit 5 (Week 6 - Post Light Treatment)
timeFrame: Visit 5 (Week 6 - post light treatment)
measure: Stinging/Burning at Visit 7 (Week 9 - Before Study Drug Application)
timeFrame: Visit 7 (Week 9 - before study drug application)
measure: Stinging/Burning at Visit 7 (Week 9 - Prior to Light Treatment)
timeFrame: Visit 7 (Week 9 - prior to light treatment)
measure: Stinging/Burning at Visit 7 (Week 9 - During Light Treatment)
timeFrame: Visit 7 (Week 9 - during light treatment)
measure: Stinging/Burning at Visit 7 (Week 9 - Post Light Treatment)
timeFrame: Visit 7 (Week 9 - post light treatment)
measure: Stinging/Burning at Visit 9 (3 Weeks After Final PDT)
timeFrame: Visit 9 (3 Weeks after Final PDT)
measure: Stinging/Burning at Visit 10 (6 Weeks After Final PDT)
timeFrame: Visit 10 (6 Weeks after Final PDT)
measure: Scaling and Dryness 48 Hours After PDT #1
timeFrame: 48 hours after PDT #1
measure: Scaling and Dryness at Visit 3 (Week 3)
timeFrame: Visit 3 (Week 3)
measure: Scaling and Dryness at Visit 5 (Week 6)
timeFrame: Visit 5 (Week 6)
measure: Scaling and Dryness at Visit 7 (Week 9)
timeFrame: Visit 7 (Week 9)
measure: Scaling and Dryness at Visit 9 (3 Weeks After Final PDT)
timeFrame: Visit 9 (3 Weeks after Final PDT)
measure: Scaling and Dryness at Visit 10 (6 Weeks After Final PDT)
timeFrame: Visit 10 (6 Weeks after Final PDT)
measure: Oozing/Vesiculation/Crusting 48 Hours After PDT #1
timeFrame: 48 hours after PDT #1
measure: Oozing/Vesiculation/Crusting at Visit 3 (Week 3)
timeFrame: Visit 3 (Week 3)
measure: Oozing/Vesiculation/Crusting at Visit 5 (Week 6)
timeFrame: Visit 5 (Week 6)
measure: Oozing/Vesiculation/Crusting at Visit 7 (Week 9)
timeFrame: Visit 7 (Week 9)
measure: Oozing/Vesiculation/Crusting at Visit 9 (3 Weeks After Final PDT)
timeFrame: Visit 9 (3 Weeks after Final PDT)
measure: Oozing/Vesiculation/Crusting at Visit 10 (6 Weeks After Final PDT)
timeFrame: Visit 10 (6 Weeks after Final PDT)
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: Burke Pharmaceutical Research
state: Arkansas
city: San Diego
country: United States
facility: Therapeutics Clinical Research
state: California
city: Denver
country: United States
facility: Cherry Creek Research, Inc.
state: Colorado
city: West Palm Beach
country: United States
facility: Kenneth R. Beer, M.D. P.A.
state: Florida
city: Snellville
country: United States
facility: Gwinnett Clinical Research Center, Inc.
state: Georgia
city: Carmel
country: United States
facility: Laser and Skin Surger Center of Indiana
state: Indiana
city: Louisville
country: United States
facility: Derm Research PLLC
state: Kentucky
city: Fridley
country: United States
facility: Minnesota Clinical Study Center
state: Minnesota
city: Brooklyn
country: United States
facility: Downstate Med Ctr
state: New York
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Clinical Research Center
state: Tennessee
city: Austin
country: United States
facility: Derm Research Inc
state: Texas
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Salt Lake City
country: United States
facility: Dermatology Research Center, Inc.
state: Utah
Study officials:
affiliation: Sponsor GmbH
name: Stuart Marcus, M.D., PhD
role: STUDY_DIRECTOR
References: