Open Label Study to Assess the Effect of Secukinumab in Moderate to Severe Papulopustular Rosacea

• Sponsor: Anne Chang (Other)
• Overall Status: Completed
• CT.gov ID: NCT03079531
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arm: 1
• Actual Duration (Months): 19.2
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Papulopustular Rosacea	Drug: Secukinumab	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Phase 1b Study of Secukinumab in Patients With Moderate to Severe Papulopustular Rosacea
• Actual Study Start Date: Jun 21, 2017
• Actual Primary Completion Date: Jan 25, 2019
• Actual Study Completion Date: Jan 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Secukinumab arm Participants receive secukinumab (7 doses over a 16-week study period).	Drug: Secukinumab; Secukinumab 300 mg administered subcutaneously.; Other Names: Tremfya

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Change From Baseline Papule/Pustule Count at Week 12 [Baseline, week 12]

   The total number of papules and pustules on the patient was assessed.

2. 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).

3. 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).

4. 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.

5. Count of Participants With ≥ Grade 3 Adverse Events [16 weeks]

6. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Dermatology	Redwood City	California	United States	94603

Sponsors and Collaborators

• Anne Chang

Investigators

• Principal Investigator: Anne Chang, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 15, 2017

More Information

Publications

• Blauvelt A, Prinz JC, Gottlieb AB, Kingo K, Sofen H, Ruer-Mulard M, Singh V, Pathan R, Papavassilis C, Cooper S; FEATURE Study Group. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015 Feb;172(2):484-93. doi: 10.1111/bjd.13348. Epub 2014 Dec 11.
• Buhl T, Sulk M, Nowak P, Buddenkotte J, McDonald I, Aubert J, Carlavan I, Déret S, Reiniche P, Rivier M, Voegel JJ, Steinhoff M. Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1/Th17 Pathways. J Invest Dermatol. 2015 Sep;135(9):2198-2208. doi: 10.1038/jid.2015.141. Epub 2015 Apr 7.
• Chang ALS, Raber I, Xu J, Li R, Spitale R, Chen J, Kiefer AK, Tian C, Eriksson NK, Hinds DA, Tung JY. Assessment of the genetic basis of rosacea by genome-wide association study. J Invest Dermatol. 2015 Jun;135(6):1548-1555. doi: 10.1038/jid.2015.53. Epub 2015 Feb 19.
• Moustafa F, Hopkinson D, Huang KE, Feldman S. Prevalence of rosacea in community settings. J Cutan Med Surg. 2015 Mar-Apr;19(2):149-52. doi: 10.2310/7750.2014.14087. Epub 2015 Mar 11.

• Responsible Party: Anne Chang, Associate Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT03079531
• Other Study ID Numbers: e-protocol 38599
• First Posted: Mar 14, 2017
• Last Update Posted: Feb 5, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Rosacea

Study Results

Participant Flow

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Period Title: Overall Study
STARTED	24
Attended ≥1 Post-baseline Visit	23
COMPLETED	17
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Overall Participants	23
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	14 60.9%
Male	9 39.1%
Race/Ethnicity, Customized (Count of Participants)
White	18 78.3%
Black	1 4.3%
Hispanic/Latino	2 8.7%
Asian	1 4.3%
Two or More Races	1 4.3%
Region of Enrollment (participants) [Number]
United States	23 100%
Papule/pustule count (papules and pustules) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [papules and pustules]	13.00
Clinician's Global Severity Score for Rosacea (score on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [score on a scale]	1.83
Clinician's Global Erythema Assessment Score (score on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [score on a scale]	1.67
Rosacea Quality of Life (RosaQoL) Score (score on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [score on a scale]	3.48
Immune Infiltrates in Papulopustular Rosacea Lesions (score on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [score on a scale]	2.50

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Papule/Pustule Count at Week 16
Description	The total number of papules and pustules on the patient was assessed.
Time Frame	Baseline, week 16

Outcome Measure Data

Analysis Population Description

Participants who completed through week 16 are included in the analysis.

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Measure Participants	17
Median (Inter-Quartile Range) [papules and pustules]	-5.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Secukinumab Arm
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Wilcoxon signed rank test
	Comments

2. Secondary Outcome

Title	Change From Baseline Papule/Pustule Count at Week 12
Description	The total number of papules and pustules on the patient was assessed.
Time Frame	Baseline, week 12

Outcome Measure Data

Analysis Population Description

Participants who completed through week 12 are included in the analysis.

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Measure Participants	17
Median (Inter-Quartile Range) [papules and pustules]	-7.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Secukinumab Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Wilcoxon signed rank test
	Comments

3. Secondary Outcome

Title	Change From Baseline in Clinician's Global Severity Score for Rosacea at Week 16
Description	Scale range: 0-4 (0=none to very mild; 1=mild; 2=moderate; 3=severe; 4=very severe).
Time Frame	Baseline, week 16

Outcome Measure Data

Analysis Population Description

Participants who completed through week 16 are included in the analysis.

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Measure Participants	17
Median (Inter-Quartile Range) [score on a scale]	-0.33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Secukinumab Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Wilcoxon signed rank test
	Comments

4. Secondary Outcome

Title	Change From Baseline in Clinician's Global Erythema Assessment Score at Week 16
Description	Scale range: 0-4 (0=none; 1=mild; 2=moderate; 3=significant; 4=severe).
Time Frame	Baseline, week 16

Outcome Measure Data

Analysis Population Description

Participants who completed through week 16 are included in the analysis.

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Measure Participants	17
Median (Inter-Quartile Range) [score on a scale]	-0.33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Secukinumab Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2
	Comments
	Method	Wilcoxon signed rank test
	Comments

5. Secondary Outcome

Title	Change From Baseline in Rosacea Quality of Life (RosaQoL) Score at Week 16
Description	Scale range: 0-5 with greater scores denoting worse quality of life.
Time Frame	Baseline, week 16

Outcome Measure Data

Analysis Population Description

Participants who completed through week 16 are included in the analysis.

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Measure Participants	17
Median (Inter-Quartile Range) [score on a scale]	-0.61

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Secukinumab Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon signed rank test
	Comments

6. Secondary Outcome

Title	Count of Participants With ≥ Grade 3 Adverse Events
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Measure Participants	24
Count of Participants [Participants]	0 0%

7. Secondary Outcome

Title	Change From Baseline in Immune Infiltrates in Papulopustular Rosacea Lesions at Week 16
Description	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

Outcome Measure Data

Analysis Population Description

Participants who contributed skin biopsies at both week 0 and week 16 are included in the analysis.

Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
Measure Participants	7
Median (Inter-Quartile Range) [score on a scale]	0.43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Secukinumab Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Wilcoxon signed rank test
	Comments

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Secukinumab Arm
Arm/Group Description	Secukinumab 300 mg administered subcutaneously (7 doses over a 16-week study period).
All Cause Mortality
	Secukinumab Arm
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Serious Adverse Events
	Secukinumab Arm
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Other (Not Including Serious) Adverse Events
	Secukinumab Arm
	Affected / at Risk (%)	# Events
Total	11/24 (45.8%)
Ear and labyrinth disorders
Hearing impaired	1/24 (4.2%)
Gastrointestinal disorders
Diarrhea	3/24 (12.5%)
Vomiting	1/24 (4.2%)
General disorders
Fatigue	3/24 (12.5%)
Flu like symptoma	1/24 (4.2%)
Injection site reaction	1/24 (4.2%)
Infections and infestations
Skin or nail infection	4/24 (16.7%)
Otitis externa	1/24 (4.2%)
Sinusitis	1/24 (4.2%)
Urinary tract infection	1/24 (4.2%)
Gastrointestinal infection	1/24 (4.2%)
Upper respiratory infection	1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/24 (4.2%)
Renal and urinary disorders
Dysuria	1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Sore throat	2/24 (8.3%)
Cough	1/24 (4.2%)
Sinus pain	1/24 (4.2%)
Sinus disorder	1/24 (4.2%)
Allergic rhinitis	1/24 (4.2%)
Skin and subcutaneous tissue disorders
Pruritus	3/24 (12.5%)
Rash (eczema)	2/24 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.