Trial Outcomes & Findings for Study of Dupilumab in Adult Patients With Extrinsic Moderate-to-Severe Atopic Dermatitis (NCT NCT01548404)

Last Updated: 2018-08-10

Results Overview

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

109 participants

Primary outcome timeframe

Baseline to Week 12

Results posted on

2018-08-10

Participant Flow

The study was conducted at 25 sites in Europe between 3 April 2012 and 25 June 2013. A total of 153 participants were screened in the study.

Out of 153 participants, 109 were randomized and treated in the study. Participants were randomized in 1:1 ratio to receive either Dupilumab 300 mg or placebo.

Participant milestones

Participant milestones
Measure	Placebo Placebo (for Dupilumab) once weekly for 12 weeks by subcutaneous (SC) injection.	Dupilumab 300 mg Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Overall Study STARTED	54	55
Overall Study COMPLETED	24	41
Overall Study NOT COMPLETED	30	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo (for Dupilumab) once weekly for 12 weeks by subcutaneous (SC) injection.	Dupilumab 300 mg Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Overall Study Adverse Event	3	1
Overall Study Physician Decision	2	1
Overall Study Inadequate response to study treatment	23	7
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	0	3
Overall Study Other than specified above	0	2

Baseline Characteristics

Study of Dupilumab in Adult Patients With Extrinsic Moderate-to-Severe Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.	Total n=109 Participants Total of all reporting groups
Age, Continuous	39.4 years STANDARD_DEVIATION 12.29 • n=99 Participants	33.7 years STANDARD_DEVIATION 10.41 • n=107 Participants	36.5 years STANDARD_DEVIATION 11.69 • n=206 Participants
Sex: Female, Male Female	27 Participants n=99 Participants	24 Participants n=107 Participants	51 Participants n=206 Participants
Sex: Female, Male Male	27 Participants n=99 Participants	31 Participants n=107 Participants	58 Participants n=206 Participants
Eczema Area and Severity Index (EASI) Score	30.8 units on a scale STANDARD_DEVIATION 13.63 • n=99 Participants	28.4 units on a scale STANDARD_DEVIATION 13.57 • n=107 Participants	29.6 units on a scale STANDARD_DEVIATION 13.59 • n=206 Participants
Investigator's Global Assessment (IGA) Score	4.0 units on a scale STANDARD_DEVIATION 0.69 • n=99 Participants	3.9 units on a scale STANDARD_DEVIATION 0.67 • n=107 Participants	3.9 units on a scale STANDARD_DEVIATION 0.68 • n=206 Participants
Scoring Atopic Dermatitis (SCORAD) Score	69.1 units on a scale STANDARD_DEVIATION 13.38 • n=99 Participants	66.7 units on a scale STANDARD_DEVIATION 13.82 • n=107 Participants	67.9 units on a scale STANDARD_DEVIATION 13.59 • n=206 Participants
Body Surface Area (BSA)	50.8 percentage of BSA STANDARD_DEVIATION 24.13 • n=99 Participants	46.8 percentage of BSA STANDARD_DEVIATION 24.55 • n=107 Participants	48.8 percentage of BSA STANDARD_DEVIATION 24.32 • n=206 Participants
5-D Pruritus Scale	18.7 units on a scale STANDARD_DEVIATION 3.50 • n=99 Participants	18.4 units on a scale STANDARD_DEVIATION 3.04 • n=107 Participants	18.5 units on a scale STANDARD_DEVIATION 3.26 • n=206 Participants
Pruritus Numerical Rating Scale (NRS) Score	5.8 units on a scale STANDARD_DEVIATION 1.93 • n=99 Participants	6.1 units on a scale STANDARD_DEVIATION 1.34 • n=107 Participants	5.9 units on a scale STANDARD_DEVIATION 1.66 • n=206 Participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: Full analysis set (FAS) population included all randomized participants who received at least one dose of study drug and had at least 1 post-baseline efficacy assessment.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 12- Last Observation Carried Forward (LOCF)	-23.3 percent change Standard Deviation 49.26	-74.0 percent change Standard Deviation 26.94

SECONDARY outcome

Timeframe: Week 12

Population: FAS population.

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" at Week 12- LOCF	7.4 percentage of participants	40.0 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS population.

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 12. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI-50) at Week 12- LOCF	35.2 Percentage of participants	85.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: FAS population.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Change From Baseline in EASI Score at Week 12- LOCF	-6.4 Units on a scale Standard Deviation 14.85	-19.9 Units on a scale Standard Deviation 11.52

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: FAS population.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Percent Change From Baseline in IGA Score at Week 12- LOCF	-14.7 Percent change Standard Deviation 27.37	-49.5 Percent change Standard Deviation 25.94

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: FAS population.

BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 12 - LOCF	-9.0 Percentage of BSA Standard Deviation 21.07	-27.4 Percentage of BSA Standard Deviation 22.81

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: FAS population.

SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 12- LOCF	-9.8 Units on a scale Standard Deviation 20.53	-35.0 Units on a scale Standard Deviation 19.43

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: FAS population. Number of participants analyzed = participants with available data for this endpoint.

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=54 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Change From Baseline in Pruritus Numerical Rating Scale (NRS) to Week 12- LOCF	-0.9 units on a scale Standard Deviation 2.07	-3.5 units on a scale Standard Deviation 2.00

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: FAS population.

The 5-D Pruritus Scale is a 1-page, 5-question tool used in clinical trials to assess 5 dimensions of background itch: degree, duration, direction, disability, and distribution. Each question corresponds to 1 of the 5 dimensions of itch; participants were to rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected. After the summation of individual score, the total score ranges from 5 (least affected) to 25 (most affected).

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 Participants Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Change From Baseline in 5-D Pruritus Scale at Week 12	-1.9 units on a scale Standard Deviation 4.28	-7.4 units on a scale Standard Deviation 4.33

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 31 other events

Deaths: 0 deaths

Dupilumab 300 mg

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=54 participants at risk Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 participants at risk Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Cardiac disorders Angina pectoris	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Infections and infestations Cellulitis	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Infections and infestations Eczema herpeticum	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Infections and infestations Skin bacterial infection	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/54 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	1.8% 1/55 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Renal and urinary disorders Renal failure	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Respiratory, thoracic and mediastinal disorders Asthmatic crisis	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Respiratory, thoracic and mediastinal disorders Lung disorder	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Skin and subcutaneous tissue disorders Dermatitis atopic	7.4% 4/54 • Number of events 5 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).

Other adverse events

Additional Information

Clinical Trial Management

Regeneron Pharmaceuticals, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=54 participants at risk Placebo (for Dupilumab) once weekly for 12 weeks by SC injection.	Dupilumab 300 mg n=55 participants at risk Dupilumab 300 mg once weekly for 12 weeks by SC injection.
Blood and lymphatic system disorders Eosinophilia	5.6% 3/54 • Number of events 3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Blood and lymphatic system disorders Lymphadenopathy	7.4% 4/54 • Number of events 4 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Eye disorders Conjunctivitis allergic	0.00% 0/54 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	9.1% 5/55 • Number of events 5 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Gastrointestinal disorders Nausea	7.4% 4/54 • Number of events 7 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	1.8% 1/55 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
General disorders Fatigue	7.4% 4/54 • Number of events 5 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	9.1% 5/55 • Number of events 7 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
General disorders Injection site erythema	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	7.3% 4/55 • Number of events 7 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
General disorders Injection site induration	5.6% 3/54 • Number of events 3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	9.1% 5/55 • Number of events 6 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
General disorders Injection site reaction	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	5.5% 3/55 • Number of events 6 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Infections and infestations Conjunctivitis	3.7% 2/54 • Number of events 2 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	14.5% 8/55 • Number of events 11 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Infections and infestations Impetigo	5.6% 3/54 • Number of events 3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	1.8% 1/55 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Infections and infestations Nasopharyngitis	18.5% 10/54 • Number of events 15 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	40.0% 22/55 • Number of events 33 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Infections and infestations Oral herpes	0.00% 0/54 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	5.5% 3/55 • Number of events 4 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Infections and infestations Rhinitis	3.7% 2/54 • Number of events 3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	5.5% 3/55 • Number of events 3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Investigations Neutrophil count increased	5.6% 3/54 • Number of events 4 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	0.00% 0/55 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Investigations White blood cell count increased	5.6% 3/54 • Number of events 4 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	1.8% 1/55 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/54 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	5.5% 3/55 • Number of events 3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Nervous system disorders Headache	13.0% 7/54 • Number of events 11 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	16.4% 9/55 • Number of events 12 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/54 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	5.5% 3/55 • Number of events 4 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.9% 1/54 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).	5.5% 3/55 • Number of events 3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product. Reported adverse events (AEs) are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug through the end of study (Day 197).