Papulopustular Rosacea
Conditions
Brief summary
This is a study to determine whether secukinumab is a potential therapy for those with papulopustular rosacea. We will observe whether this drug decreases the size and/or amount and severity of the pustules of those who suffer from rosacea.
Detailed description
Rosacea is a common inflammatory skin disease affecting up to 10% of adults. Despite this, the etiology of rosacea is unclear, although there may be a genetic predisposition (Chang et al., 2015). Currently, there is no cure. Rosacea can lead to scarring, itching, burning, and is associated with anxiety and depression (Moustafa et al., 2015), significantly affecting quality of life. Secukinumab is an antibody that binds to a protein (interleukin (IL)-17A) that is involved in inflammation. When IL-17A is bound to secukinumab, it cannot bind to its receptor, thereby inhibiting its ability to feed the inflammatory response. In clinical trials, secukinumab has been effective for moderate to severe psoriasis (Blauvelt et al., 2015). Recently, human data from all types of rosacea have shown Th1/Th17 polarization profile of the T-cell response, suggesting that anti-IL-17 therapy may be beneficial for rosacea (Buhl et al., 2015). Hence, secukinumab could be effective against rosacea. This proposal is a proof-of-concept study to use secukinumab in open label design for moderate to severe papulopustular rosacea.
Interventions
DRUGSecukinumab
Secukinumab 300 mg administered subcutaneously.
Sponsors
Anne Chang
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* moderate to severe papulopustular rosacea defined clinically using the grading system of Wilkin et al. (2004) as having at least ten lesions (either papules or pustules) on face at time of enrollment * age 18 years or greater willing and able to understand and sign informed consent form
Exclusion criteria
* known hypersensitivity to secukinumab * topical or oral anti-rosacea medication usage for 28 days prior to enrollment * active Crohn's disease, as secukinumab may exacerbate this disease * active infection including tuberculosis, hepatitis B or C, human immunodeficiency virus * participants with latent tuberculosis will need to have treatment initiated prior to starting study drug * pregnant or lactating * active and/or uncontrolled medical conditions that may interfere with study procedures or obscure rosacea assessment such as cutaneous lupus * use of retinoids within past 3 months of enrollment * use of antibiotics within 4 weeks of enrollment * use of light based or laser treatment to face within 8 weeks of enrollment * use of topical or systemic steroids within 4 weeks of enrollment * acne conglobate, acne fulminans, chloracne, severe acne requiring systemic treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Papule/Pustule Count at Week 16 | Baseline, week 16 | The total number of papules and pustules on the patient was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinician's Global Severity Score for Rosacea at Week 16 | Baseline, week 16 | Scale range: 0-4 (0=none to very mild; 1=mild; 2=moderate; 3=severe; 4=very severe). |
| Change From Baseline in Clinician's Global Erythema Assessment Score at Week 16 | Baseline, week 16 | Scale range: 0-4 (0=none; 1=mild; 2=moderate; 3=significant; 4=severe). |
| Change From Baseline Papule/Pustule Count at Week 12 | Baseline, week 12 | The total number of papules and pustules on the patient was assessed. |
| Count of Participants With ≥ Grade 3 Adverse Events | 16 weeks | — |
| Change From Baseline in Immune Infiltrates in Papulopustular Rosacea Lesions at Week 16 | Baseline, week 16 | Immune infiltrates as assessed by immunohistochemistry, using a semi-quantitative grading scale for histological inflammation (scale range: 0-4, with 0-normal to 4-widespread inflammation). |
| Change From Baseline in Rosacea Quality of Life (RosaQoL) Score at Week 16 | Baseline, week 16 | Scale range: 0-5 with greater scores denoting worse quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab Arm Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period). | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Secukinumab Arm |
|---|---|
| Age, Continuous | 56 years |
| Clinician's Global Erythema Assessment Score | 1.67 score on a scale |
| Clinician's Global Severity Score for Rosacea | 1.83 score on a scale |
| Immune Infiltrates in Papulopustular Rosacea Lesions | 2.50 score on a scale |
| Papule/pustule count | 13.00 papules and pustules |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 2 Participants |
| Race/Ethnicity, Customized Two or More Races | 1 Participants |
| Race/Ethnicity, Customized White | 18 Participants |
| Region of Enrollment United States | 23 participants |
| Rosacea Quality of Life (RosaQoL) Score | 3.48 score on a scale |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 11 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Change From Baseline in Papule/Pustule Count at Week 16
The total number of papules and pustules on the patient was assessed.
Time frame: Baseline, week 16
Population: Participants who completed through week 16 are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Secukinumab Arm | Change From Baseline in Papule/Pustule Count at Week 16 | -5.00 papules and pustules |
Comparison: The null hypothesis is that there would be no difference in papule/pustule count at baseline and after 16 weeks of secukinumab; the alternative hypothesis is that there would be a difference. Using an alpha=0.05 and power=0.80 (two sided test), the sample size needed would be 20. Assuming a dropout rate of 20%, 24 patients would be needed to achieve sufficient sample size.p-value: 0.01Wilcoxon signed rank test
Secondary
Change From Baseline in Clinician's Global Erythema Assessment Score at Week 16
Scale range: 0-4 (0=none; 1=mild; 2=moderate; 3=significant; 4=severe).
Time frame: Baseline, week 16
Population: Participants who completed through week 16 are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Secukinumab Arm | Change From Baseline in Clinician's Global Erythema Assessment Score at Week 16 | -0.33 score on a scale |
p-value: 0.2Wilcoxon signed rank test
Secondary
Change From Baseline in Clinician's Global Severity Score for Rosacea at Week 16
Scale range: 0-4 (0=none to very mild; 1=mild; 2=moderate; 3=severe; 4=very severe).
Time frame: Baseline, week 16
Population: Participants who completed through week 16 are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Secukinumab Arm | Change From Baseline in Clinician's Global Severity Score for Rosacea at Week 16 | -0.33 score on a scale |
p-value: 0.03Wilcoxon signed rank test
Secondary
Change From Baseline in Immune Infiltrates in Papulopustular Rosacea Lesions at Week 16
Immune infiltrates as assessed by immunohistochemistry, using a semi-quantitative grading scale for histological inflammation (scale range: 0-4, with 0-normal to 4-widespread inflammation).
Time frame: Baseline, week 16
Population: Participants who contributed skin biopsies at both week 0 and week 16 are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Secukinumab Arm | Change From Baseline in Immune Infiltrates in Papulopustular Rosacea Lesions at Week 16 | 0.43 score on a scale |
p-value: 0.56Wilcoxon signed rank test
Secondary
Change From Baseline in Rosacea Quality of Life (RosaQoL) Score at Week 16
Scale range: 0-5 with greater scores denoting worse quality of life.
Time frame: Baseline, week 16
Population: Participants who completed through week 16 are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Secukinumab Arm | Change From Baseline in Rosacea Quality of Life (RosaQoL) Score at Week 16 | -0.61 score on a scale |
p-value: <0.001Wilcoxon signed rank test
Secondary
Change From Baseline Papule/Pustule Count at Week 12
The total number of papules and pustules on the patient was assessed.
Time frame: Baseline, week 12
Population: Participants who completed through week 12 are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Secukinumab Arm | Change From Baseline Papule/Pustule Count at Week 12 | -7.00 papules and pustules |
p-value: 0.02Wilcoxon signed rank test
Secondary
Count of Participants With ≥ Grade 3 Adverse Events
Time frame: 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab Arm | Count of Participants With ≥ Grade 3 Adverse Events | 0 Participants |