Papulopustular Rosacea, Rosacea
Conditions
Keywords
Rosacea, Photodynamic Therapy, Aminolevulinic Acid, Papulopustular Rosacea, Blue Light
Brief summary
Rosacea is a chronic inflammatory disorder that is characterized by severe flushing (transient erythema), non-transient erythema, papules, pustules, and telangiectasia. Topical therapy is not always effective in treating symptoms of rosacea. Furthermore, rapid recurrence is common following the use of systemic antibiotics, resulting in the chronic use of these medications to control the disease. Although the exact pathogenesis of rosacea is unknown, treatment for this condition has been investigated based on its similarity to acne and photodamaged skin. Case reports have shown promising results in rosacea patients treated with methyl aminolevulinate photodynamic therapy (MAL - PDT). Other than a case report which observed significant improvement of papules, pustules, erythema, and flushing following 5 - aminolevulinic acid photodynamic therapy (ALA-PDT) treatment of a patient with rosacea, the role of ALA-PDT in the treatment of rosacea has not been reported. We have designed a pilot study investigating the efficacy of ALA-PDT in treating papulopustular rosacea. The objectives of the study are as follows: Primary objective: 1. To evaluate improvement of the inflammatory lesions (papules, pustules, nodules), erythema, and telangiectasia of rosacea as assessed by the Investigator's Global Assessment (IGA). 2. To evaluate improvement of the inflammatory lesions (papules, pustules, nodules) of rosacea as assessed by the Inflammatory Lesion Investigator's Global Assessment (ILIGA). Secondary objectives: 3. To evaluate improvement of rosacea associated erythema as assessed by the Clinical Erythema Assessment (CEA) scale. 4. To evaluate improvement of the inflammatory lesions (papules, pustules, nodules) of rosacea as measured by a difference in inflammatory lesion count. 5. To evaluate improvement of rosacea as assessed by the Patient Overall Assessment Scale.
Interventions
DRUGAminolevulinic acid topical solution 20%
Intervention used in the experimental arm only
DEVICEBlu-U Light Therapy
Intervention used in experimental and sham arms
OTHERPlacebo vehicle only
Intervention only includes the placebo vehicle solution
Sponsors
DUSA Pharmaceuticals, Inc.
George Washington University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
1. Ages 18-79 years 2. Clinical diagnosis of papulopustular rosacea based on physician evaluation. Only patients with 3-50 papules and/or pustules, and a CEA total score ≥ 5, (See Section 4.1.3) will be enrolled. 3. History of failing at least one conventional treatment for rosacea (metronidazole, sodium sulfacetamide, tetracycline, azelaic acid) or not interested in continuous treatment with these agents.
Exclusion criteria
1. \< 18 or \> 79 years of age 2. Allergy to 5 - aminolevulinic acid (ALA) or any component of the vehicle 3. Use of topical acne or rosacea treatments (on the face) within 2 weeks prior to Visit 1 4. Use of systemic antibiotics within 1 month prior to Visit 1 5. Use of topical retinoids (on the face) within 1 month prior to Visit 1 6. Use of systemic retinoids, including isotretinoin, within 6 months prior to Visit 1. 7. Use of laser or light based rosacea treatments (on the face) within 1 month prior to Visit 1 8. Cosmetic procedures (e.g., superficial chemical peels, exfoliation or microdermabrasion of the face) within 2 months prior to Visit 1 9. Use of topical corticosteroids (on the face) 1 month prior to Visit 1 10. Use of systemic corticosteroids 3 months prior to Visit 1 11. Known or suspected history of drug or alcohol abuse within the past 6 months as determined by the medical record or patient interview 12. History of adverse reaction to light exposure 13. History of disorder of porphyrin metabolism 14. Scarring or infection in the area being treated 15. Extensive facial hair that would either impair blue light exposure or interfere with lesion evaluation 16. Inability to make study visits or anticipated poor compliance 17. Pregnant females or nursing mothers. Eligible women of reproductive age will be required to have a negative urine pregnancy test at screening. They will also be required to be on at least one reliable form of effective birth control \[examples: barrier method (condoms, diaphragm), oral, injectable, implant birth control or abstinence\] during the course of this study and 30 days following the last treatment period. 18. Life threatening illness that would interfere with the patient's ability to complete the study 19. Participation in another clinical experimental therapeutic study within 30 days of screening visit 20. Any history or evidence of severe illness or any other condition that would make the patient, in the opinion of the investigator, unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules), Erythema, and Telangiectasia of Rosacea as Assessed by the Investigator's Global Assessment (IGA) | 17 weeks | The Investigator's global assessment (IGA) of rosacea is a subjective 7-point, static scoring system. Scores range from 0 to 6: 0 (clear), 1 (minimal), 2 (mild), 3 (mild to moderate), 4 (moderate), 5 (moderate to severe), 6 (severe). |
| Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Assessed by the Inflammatory Lesion Investigator's Global Assessment (ILIGA) | 17 weeks | The Inflammatory Lesion Investigator's Global Assessment (ILIGA) is a subjective 5-point measure of the overall disease severity. Scores range from 0 to 4: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), 4 (severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Improvement of Rosacea Associated Erythema as Assessed by the Clinical Erythema Assessment (CEA) Scale | 17 weeks | The Clinical Erythema Assessment (CEA) scale is an assessment of erythema. It has a score range from 0 to 4: 0 (none), 1 (mild), 2 (moderate), 3 (significant), 4 (severe). The total score is based on the evaluation of all areas of the face (forehead, chin, right cheek, left cheek, and nose). Each of these areas were scored from 0-4, giving a maximum total score of 20. |
| Evaluate Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Measured by a Difference in Inflammatory Lesion Count (ILC) | 17 weeks | The Inflammatory Lesion Count (ILC) is calculated by the number of inflammatory lesions (papules, pustules, nodules) as recorded by the investigator. |
| Evaluate Improvement of Rosacea as Assessed by the Patient Overall Assessment (POA) Scale | 17 weeks | For the Patient Overall Assessments (POA) scale, patients assessed the overall improvement of their rosacea using a 4-point scale, where 1 = excellent improvement, 2 = good/moderate improvement, 3 = no change, 4 = worsening. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levulan and Blu-U Light Entire face treated with 20% Aminolevulinic Acid (Levulan) and Blu-U light
Aminolevulinic acid topical solution 20%: Intervention used in the experimental arm only
Blu-U Light Therapy: Intervention used in experimental and sham arms | 10 |
| Vehicle and Blu-U Light Entire face treated with vehicle substance only and Blu-U light
Blu-U Light Therapy: Intervention used in experimental and sham arms | 10 |
| Vehicle Only Entire face treated with vehicle substance only
Placebo vehicle only: Intervention only includes the placebo vehicle solution | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Levulan and Blu-U Light | Vehicle and Blu-U Light | Vehicle Only | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 9 Participants | 28 Participants |
| Fitzpatrick Skin Type I | 2 Participants | 6 Participants | 1 Participants | 9 Participants |
| Fitzpatrick Skin Type II | 5 Participants | 4 Participants | 9 Participants | 18 Participants |
| Fitzpatrick Skin Type III | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Fitzpatrick Skin Type IV | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick Skin Type V | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Fitzpatrick Skin Type VI | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 10 Participants | 28 Participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 3 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules), Erythema, and Telangiectasia of Rosacea as Assessed by the Investigator's Global Assessment (IGA)
The Investigator's global assessment (IGA) of rosacea is a subjective 7-point, static scoring system. Scores range from 0 to 6: 0 (clear), 1 (minimal), 2 (mild), 3 (mild to moderate), 4 (moderate), 5 (moderate to severe), 6 (severe).
Time frame: 17 weeks
Population: Group A = Levulan and Blu-U Light; Group B = Vehicle and Blu-U Light; Group C = Vehicle Only. Of the 30 randomized patients, 24 (80%) completed the entire study. 8 (80%) patients completed from Group A, 10 (100%) from Group B, and 6 (60%) from Group C.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levulan and Blu-U Light | Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules), Erythema, and Telangiectasia of Rosacea as Assessed by the Investigator's Global Assessment (IGA) | 2.8 score on a scale | Standard Deviation 0.5 |
| Vehicle and Blu-U Light | Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules), Erythema, and Telangiectasia of Rosacea as Assessed by the Investigator's Global Assessment (IGA) | 1.5 score on a scale | Standard Deviation 1.6 |
| Vehicle Only | Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules), Erythema, and Telangiectasia of Rosacea as Assessed by the Investigator's Global Assessment (IGA) | 1.5 score on a scale | Standard Deviation 0.8 |
Primary
Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Assessed by the Inflammatory Lesion Investigator's Global Assessment (ILIGA)
The Inflammatory Lesion Investigator's Global Assessment (ILIGA) is a subjective 5-point measure of the overall disease severity. Scores range from 0 to 4: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), 4 (severe).
Time frame: 17 weeks
Population: Group A = Levulan and Blu-U Light; Group B = Vehicle and Blu-U Light; Group C = Vehicle Only. Of the 30 randomized patients, 24 (80%) completed the entire study. 8 (80%) patients completed from Group A, 10 (100%) from Group B, and 6 (60%) from Group C.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levulan and Blu-U Light | Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Assessed by the Inflammatory Lesion Investigator's Global Assessment (ILIGA) | 1.3 score on a scale | Standard Deviation 0.9 |
| Vehicle and Blu-U Light | Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Assessed by the Inflammatory Lesion Investigator's Global Assessment (ILIGA) | 0.8 score on a scale | Standard Deviation 1.2 |
| Vehicle Only | Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Assessed by the Inflammatory Lesion Investigator's Global Assessment (ILIGA) | 1.0 score on a scale | Standard Deviation 0.9 |
Secondary
Evaluate Improvement of Rosacea as Assessed by the Patient Overall Assessment (POA) Scale
For the Patient Overall Assessments (POA) scale, patients assessed the overall improvement of their rosacea using a 4-point scale, where 1 = excellent improvement, 2 = good/moderate improvement, 3 = no change, 4 = worsening.
Time frame: 17 weeks
Population: Group A = Levulan and Blu-U Light; Group B = Vehicle and Blu-U Light; Group C = Vehicle Only. 8 (80%) patients completed from Group A, 10 (100%) from Group B, and 6 (60%) from Group C. One participant in Group B did not complete the POA scale at the last follow-up visit; therefore only 9 participants are included in the analysis for Group B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levulan and Blu-U Light | Evaluate Improvement of Rosacea as Assessed by the Patient Overall Assessment (POA) Scale | 0.9 score on a scale | Standard Deviation 1 |
| Vehicle and Blu-U Light | Evaluate Improvement of Rosacea as Assessed by the Patient Overall Assessment (POA) Scale | 0.6 score on a scale | Standard Deviation 0.9 |
| Vehicle Only | Evaluate Improvement of Rosacea as Assessed by the Patient Overall Assessment (POA) Scale | 0.3 score on a scale | Standard Deviation 0.8 |
Secondary
Evaluate Improvement of Rosacea Associated Erythema as Assessed by the Clinical Erythema Assessment (CEA) Scale
The Clinical Erythema Assessment (CEA) scale is an assessment of erythema. It has a score range from 0 to 4: 0 (none), 1 (mild), 2 (moderate), 3 (significant), 4 (severe). The total score is based on the evaluation of all areas of the face (forehead, chin, right cheek, left cheek, and nose). Each of these areas were scored from 0-4, giving a maximum total score of 20.
Time frame: 17 weeks
Population: Group A = Levulan and Blu-U Light; Group B = Vehicle and Blu-U Light; Group C = Vehicle Only. Of the 30 randomized patients, 24 (80%) completed the entire study. 8 (80%) patients completed from Group A, 10 (100%) from Group B, and 6 (60%) from Group C.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levulan and Blu-U Light | Evaluate Improvement of Rosacea Associated Erythema as Assessed by the Clinical Erythema Assessment (CEA) Scale | 6.0 score on a scale | Standard Deviation 2.1 |
| Vehicle and Blu-U Light | Evaluate Improvement of Rosacea Associated Erythema as Assessed by the Clinical Erythema Assessment (CEA) Scale | 4.5 score on a scale | Standard Deviation 3.6 |
| Vehicle Only | Evaluate Improvement of Rosacea Associated Erythema as Assessed by the Clinical Erythema Assessment (CEA) Scale | 1.2 score on a scale | Standard Deviation 3.9 |
Secondary
Evaluate Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Measured by a Difference in Inflammatory Lesion Count (ILC)
The Inflammatory Lesion Count (ILC) is calculated by the number of inflammatory lesions (papules, pustules, nodules) as recorded by the investigator.
Time frame: 17 weeks
Population: Group A = Levulan and Blu-U Light; Group B = Vehicle and Blu-U Light; Group C = Vehicle Only. Of the 30 randomized patients, 24 (80%) completed the entire study. 8 (80%) patients completed from Group A, 10 (100%) from Group B, and 6 (60%) from Group C.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levulan and Blu-U Light | Evaluate Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Measured by a Difference in Inflammatory Lesion Count (ILC) | 10.8 Inflammatory Lesion Count | Standard Deviation 2.9 |
| Vehicle and Blu-U Light | Evaluate Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Measured by a Difference in Inflammatory Lesion Count (ILC) | 3.4 Inflammatory Lesion Count | Standard Deviation 7 |
| Vehicle Only | Evaluate Improvement of the Inflammatory Lesions (Papules, Pustules, Nodules) of Rosacea as Measured by a Difference in Inflammatory Lesion Count (ILC) | 6.2 Inflammatory Lesion Count | Standard Deviation 5 |