A Trial Comparing the Efficacy of Subcutaneous Injections of Brodalumab to Oral Administrations of Fumaric Acid Esters in Adults With Moderate to Severe Plaque Psoriasis

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03331835
• Collaborator: (none)
• Enrollment: 210
• Locations: 30
• Arms: 2
• Actual Duration (Months): 16.5
• Patients Per Site: 7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary objective is to demonstrate added benefit of brodalumab versus a selected systemic comparator in treatment of moderate to severe plaque psoriasis in Germany in subjects who have not previously received systemic treatment for psoriasis. > Fumaric acid esters have been selected as the comparator because it is an established systemic treatment of psoriasis in Germany.>

Condition or Disease	Intervention/Treatment	Phase
Psoriasis Vulgaris	Biological: Brodalumab; Drug: Fumaric acid esters	Phase 4

Detailed Description

A 24-week, randomised, open-label, active-controlled, parallel group, multi-centre trial with investigator-blinded efficacy assessments

Study Design

• Study Type: Interventional
• Actual Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 4 Trial Comparing the Efficacy of Subcutaneous Injections of Brodalumab to Oral Administrations of Fumaric Acid Esters in Adults With Moderate to Severe Plaque Psoriasis
• Actual Study Start Date: Nov 3, 2017
• Actual Primary Completion Date: Jan 24, 2019
• Actual Study Completion Date: Mar 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brodalumab Kyntheum® (brodalumab)> pre-filled syringe 210 mg/1.5 mL solution for subcutaneous injections.> First 3 injections are administered weekly, and hereafter every two weeks (Q2W).	Biological: Brodalumab; Brodalumab is a recombinant fully human monoclonal immunoglobulin IgG2-antibody that binds with high affinity to human interleukin 17 receptor A (IL-17RA).> Blocking IL-17RA inhibits IL-17 cytokine-induced responses and results in reduced or normalised inflammation of the skin in subjects with psoriasis.; Other Names: Kyntheum®
Active Comparator: Fumaric acid esters Fumaderm® initial dose tablets (30 mg dimethyl fumarate, 67 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt)> Fumaderm® tablets (120 mg dimethyl fumarate, 87 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt)> > Fumaderm® tablets are administered orally up to 3 times daily in accordance with the dosing scheme in the label.	Drug: Fumaric acid esters; Fumaric acid esters have been used to treat psoriasis since 1959. Systemic therapy with fumaric acid esters is based on an established dosing scheme with a gradual increase to improve tolerability, especially with regards to gastrointestinal side effects.; Other Names: Fumaderm®

Outcome Measures

Primary Outcome Measures

1. Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24 [Baseline to Week 24]

   The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).

2. Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24 [Baseline to Week 24]

   sPGA is a 6-point scale that represents the average lesion severity on the trunk and limbs. The assessment is based on the condition of the disease at the time of evaluation. Static Physician's Global Assessment is a scale ranging rom 0 (clear skin) to 5 (severe disease).

Secondary Outcome Measures

1. Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24 [Baseline to Week 24]

   The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).

2. Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24 [Baseline to Week 24]

   The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).

3. Change From Baseline at Week 24 in PASI Score [Baseline to Week 24]

   The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). A negative change in PASI score means that the PASI score was lower at the time of data collection.

4. Percent Change From Baseline in PASI Score at Week 24 [Baseline to Week 24]

   The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). A negative value in the percent change from baseline that the PASI score was lower at the time of data collection.

5. Change From Baseline at Week 24 in Affected Body Surface Area (BSA) [Baseline to Week 24]

   The surface area of the participant's hand (palm and fingers) is used as a reference measurement to calculate the percentage of each body region that is affected by psoriasis. One hand is approximately equal to 1% total BSA. Furthermore, the complete body surface area (BSA=100%) can be divided into regions that approximates percentages of BSA as follows: head and neck (10%), upper extremities (20%), the trunk including the axillae and groin (30%), and finally the lower extremities, including the buttocks (40%). A negative value in the percent change from baseline that the affected BSA was lower at the time of data collection.

6. Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1) [Week 24]

   The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score >1. Symptom-free day is defined as having daily total PSI of 0 on that day.

7. PSI Total Score of 0 at Week 24 [Week 24]

   The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score >1. Symptom-free day is defined as having daily total PSI of 0 on that day.

8. Number of Symptom-free Days From Randomisation to Week 24 [Baseline to Week 24]

   The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score >1. Symptom-free day is defined as having daily total PSI of 0 on that day.

9. Burden of Symptoms [Baseline to Week 24]

   Burden of symptoms was assessed as the normalised area under the curve (AUC) of PSI from baseline to the last available assessment. The AUC for the PSI total score was calculated for each participant using the standard trapezoidal rule. The AUC was normalised by dividing it with the time from baseline to the last available assessment of the PSI total score. The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms.

10. Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score [Baseline to Week 24]

    DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.

11. DLQI Total Score of 0 or 1 at Week 24 [Week 24]

    DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.

Other Outcome Measures

1. Change From Baseline at Week 24 in NAPSI Total Score [Baseline to Week 24]

   The Nail Psoriasis Severity Index (NAPSI) grades nails by first dividing the nail area with imaginary horizontal and vertical lines into 4 quarters. The following 8 clinical features of nail psoriasis are then scored based on the number of quarters in which the feature is present (0 to 4) to arrive at a NAPSI score of 0 to 32 for each nail: Pitting. Leukonychia. Red spots in lunula. Nail plate crumbling. Oil drop (salmon patch) discoloration. Onycholysis. Nail bed hyperkeratosis. Splinter haemorrhages. A negative change in NAPSI score means that the NAPSI score was lower at the time of data collection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Criteria for Inclusion:>

• Men or women ≥18 years of age at the time of screening.>

• Subjects with chronic plaque type psoriasis diagnosed at least 6 months before randomisation.>

• Subjects with moderate to severe plaque psoriasis in whom topical therapy is not adequate and who are candidates for systemic therapy, defined at randomisation by PASI

10, affected BSA >10%, and DLQI >10.>

• Subject has no known history of active tuberculosis.>

• Subject has a negative test for tuberculosis taken at screening (negative Quantiferon test).>

• Subject and/or subject's designee is/are capable of administering subcutaneous injections.>

Main Criteria for Exclusion:>

• Previous or current systemic treatment of plaque psoriasis or known contraindication for systemic therapy.>

• Previous or current PUVA (psoralens and ultraviolet A) therapy.>

• Washouts and non-permitted drugs:>

1. Have received phototherapy (UVA light therapy without psoralens, UVB light therapy, excimer laser, tanning beds etc. within 4 weeks of baseline, or>

2. Have had topical psoriasis treatment within 2 weeks of baseline (exceptions: bland emollients without urea or beta or alpha hydroxy acids)>

3. Have received any biologic immune modulating treatments used for indication other than psoriasis within 4 weeks of baseline or within a period of 5 half-lives of the IMP, whichever is longer>

4. Have received any other systemic immune modulating treatment (including but not limited to oral retinoids, methotrexate, calcineurin inhibitors, oral or parenteral corticosteroids etc. used for indications other than psoriasis) within 4 weeks of baseline or within a period of 5 half-lives of the IMP, whichever is longer.>

• Subjects with any of the following laboratory abnormalities at screening:>

1. Leukocyte cell count below 3×10^{9/L or lymphocyte count below 0.7×10}9/L>

2. Aspartate aminotransferase (AST) or alanine transferase (ALT) > 2× ULN (upper level of normal limit)>

3. Absolute neutrophil count < 2×10^9/L>

4. Serum creatinine > ULN.>

• History of depressive disorder within the last 2 years including current antidepressive treatment.>

• Subjects with a history of suicidal behaviour (suicide attempt). >

• Any suicidal ideation of severity 4 or 5 based on the eC-SSRS questionnaire at screening.>

• A PHQ-8 score of ≥10 corresponding to moderate to severe depression at screening.>

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fachklinik Bad Bentheim Klinik für Dermatologie	Bad Bentheim		Germany	48455
2	Charité - Universitätsmedizin Berlin Klinik für Dermatologie, Venerologie und Allergologie Psoriasis Studien Zentrum	Berlin		Germany	10117
3	Rothhaar Studien GmbH Dermatologisches Studienzentrum	Berlin		Germany	10783
4	Hautarztpraxis Dr. Wildfeuer	Berlin		Germany	13055
5	Klinikum Bielefeld Klinik für Dermatologie und Allergologie	Bielefeld		Germany	33647
6	Hauttumorzentrum Ruhr- Universität im St. Josef Hospital	Bochum		Germany	44791
7	Hautarztpraxis Dr. Niesmann und Dr. Othlinghaus	Bochum		Germany	44793
8	Universitätsklinikum Bonn (AöR) Klinik und Poliklinik für Dermatologie und Allergologie	Bonn		Germany	53127
9	Elbe Klinikum Buxtehude Klinik für Dermatologie	Buxtehude		Germany	21614
10	Rosenpark Research	Darmstadt		Germany	64283
11	Universitätsklinikum Carl Gustav Carus Klinik und Poliklinik für Dermatologie	Dresden		Germany	01307
12	Universitätsklinikum Erlangen Hautklinik	Erlangen		Germany	91054
13	Universitätsklinikum Frankfurt Klinik für Dermatologie	Frankfurt		Germany	60590
14	Derma-Study-Center-Friedrichshafen	Friedrichshafen		Germany	88045
15	Gemeinschaftspraxis Rotterdam & Kollegen Facharzt für Haut & Geschlechtskrankheiten	Gelsenkirchen		Germany	45883
16	Universitätsklinikum Hamburg-Eppendorf, Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen	Hamburg		Germany	20246
17	SCIderm GmbH	Hamburg		Germany	20354
18	Medizinische Hochschule Hannover Klinik für Dermatologie Allergologie und Venerologie	Hannover		Germany	30625
19	Universitäts-Hautklinik Heidelberg	Heidelberg		Germany	69120
20	Klinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Schleswig-Holstein, Campus Kiel Psoriasis-Zentrum	Kiel		Germany	24105
21	Exellenzzentrum Entzündungsmedizin (CCIM) Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck		Germany	23538
22	University Medical Center Mainz Department of Dermatology and Allergy, Clinical Research Center	Mainz		Germany	55131
23	Universitätsklinikum Mannheim der Universität Heidelberg Klinik für Dermatologie, Venerologie und Allergologie	Mannheim		Germany	68167
24	Technische Universität München Klinik und Poliklinik für Dermatologie und Allergologie	München		Germany	80802
25	Klinische Forschung Osnabrück - Klifos	Osnabrück		Germany	49074
26	KLINIKUM VEST GmbH Knappschaftskrankenhaus Recklinghausen Klinik für Dermatologie und Allergologie	Recklinghausen		Germany	45657
27	Gemeinschaftspraxis Weber & Crainic	Schweinfurt		Germany	97421
28	Hautarztpraxis Dres. Leitz	Stuttgart		Germany	70178
29	University Medical Center University of Tübingen	Tübingen		Germany	72076
30	Hautarztpraxis	Witten		Germany	58453

Sponsors and Collaborators

• LEO Pharma

Investigators

• Study Director: Study Director, LEO Pharma

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 17, 2018

More Information

Publications

None provided.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT03331835
• Other Study ID Numbers: LP0160-1327; 2016-003867-21
• First Posted: Nov 6, 2017
• Last Update Posted: Feb 19, 2020
• Last Verified: Feb 1, 2020

• 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.: Yes
• Additional relevant MeSH terms: Psoriasis; Brodalumab

Study Results

Participant Flow

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Kyntheum® (brodalumab) pre-filled syringe 210 mg/1.5 mL solution for subcutaneous injections. First 3 injections are administered weekly, and hereafter every two weeks (Q2W).	Fumaderm® initial dose tablets (30 mg dimethyl fumarate, 67 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt). Fumaderm® tablets (120 mg dimethyl fumarate, 87 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt). Fumaderm® tablets are administered orally up to 3 times daily in accordance with the dosing scheme in the label.
Period Title: Overall Study
STARTED	105	105
COMPLETED	91	58
NOT COMPLETED	14	47

Baseline Characteristics

Arm/Group Title	Brodalumab	Fumaric Acid Esters	Total
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).	Total of all reporting groups
Overall Participants	105	105	210
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	96 91.4%	97 92.4%	193 91.9%
>=65 years	9 8.6%	8 7.6%	17 8.1%
Sex: Female, Male (Count of Participants)
Female	32 30.5%	33 31.4%	65 31%
Male	73 69.5%	72 68.6%	145 69%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	100 95.2%	103 98.1%	203 96.7%
Unknown or Not Reported	5 4.8%	2 1.9%	7 3.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1%	0 0%	1 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	104 99%	105 100%	209 99.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Germany	105 100%	105 100%	210 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	175 (9.6)	176 (9.8)	175 (9.7)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	87.8 (20.4)	86.6 (21.1)	87.2 (20.7)
Mean weight in participants weighing <100 kg (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	78.4 (11.9)	77.2 (12.8)	77.8 (12.4)
Mean weight in participants weighing >=100 kg (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	116 (13.2)	115 (13.9)	116 (13.4)
Body mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.5 (5.7)	28.0 (6.0)	28.2 (5.9)
Duration of psoriasis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.3 (11.5)	13.2 (11.7)	13.7 (11.6)
PASI score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	17.2 (5.9)	17.8 (6.7)	17.5 (6.3)
sPGA score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	3.5 (0.6)	3.5 (0.7)	3.5 (0.6)
BSA score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	24.8 (15.2)	25.5 (14.9)	25.2 (15.1)
NAPSI score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	6.4 (4.4)	7.7 (4.9)	7.0 (4.7)
DLQI score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	18.8 (5.2)	18.5 (4.9)	18.7 (5.1)
PSI score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	14.8 (5.4)	17.9 (5.3)	16.3 (5.6)

Outcome Measures

1. Primary Outcome

Title	Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24
Description	The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	105	105
Count of Participants [Participants]	85 81%	40 38.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (≤100 kg, > 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	95% CI and p-value are derived from CMH analysis stratified by weight group at baseline (≤100 kg, > 100 kg).
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	42.86
	Confidence Interval	(2-Sided) 95%; 30.93 to 54.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24
Description	sPGA is a 6-point scale that represents the average lesion severity on the trunk and limbs. The assessment is based on the condition of the disease at the time of evaluation. Static Physician's Global Assessment is a scale ranging rom 0 (clear skin) to 5 (severe disease).
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	105	105
Count of Participants [Participants]	68 64.8%	21 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (≤100 kg, > 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	95% CI and p-value are derived from CMH analysis stratified by weight group at baseline (≤100 kg, > 100 kg)
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	44.76
	Confidence Interval	(2-Sided) 95%; 32.81 to 56.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24
Description	The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	105	105
Count of Participants [Participants]	69 65.7%	23 21.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (≤100 kg, > 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	43.81
	Confidence Interval	(2-Sided) 95%; 31.78 to 55.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24
Description	The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	105	105
Count of Participants [Participants]	42 40%	9 8.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (≤100 kg, > 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	31.43
	Confidence Interval	(2-Sided) 95%; 20.76 to 42.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline at Week 24 in PASI Score
Description	The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). A negative change in PASI score means that the PASI score was lower at the time of data collection.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The number of analysed participants is not the same as the number of randomised participants, as participants with missing data in all visits for a given endpoint are not included in the mixed model for repeated measurements (MMRM) analysis used to analyse the endpoint.

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	100	96
Mean (Standard Error) [score on a scale]	-15.69 (0.59)	-12.62 (0.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	The endpoint was analysed using mixed model for repeated measures (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups were defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.08
	Confidence Interval	(2-Sided) 95%; -4.83 to -1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percent Change From Baseline in PASI Score at Week 24
Description	The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). A negative value in the percent change from baseline that the PASI score was lower at the time of data collection.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The number of analysed participants is not the same as the number of randomised participants, as participants with missing data in all visits for a given endpoint are not included in the mixed model for repeated measurements (MMRM) analysis used to analyse the endpoint.

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	100	96
Mean (Standard Error) [percent change in PASI]	-90.03 (2.25)	-73.67 (2.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	The endpoint was analysed using mixed model for repeated measures (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups were defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-16.36
	Confidence Interval	(2-Sided) 95%; -23.03 to -9.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline at Week 24 in Affected Body Surface Area (BSA)
Description	The surface area of the participant's hand (palm and fingers) is used as a reference measurement to calculate the percentage of each body region that is affected by psoriasis. One hand is approximately equal to 1% total BSA. Furthermore, the complete body surface area (BSA=100%) can be divided into regions that approximates percentages of BSA as follows: head and neck (10%), upper extremities (20%), the trunk including the axillae and groin (30%), and finally the lower extremities, including the buttocks (40%). A negative value in the percent change from baseline that the affected BSA was lower at the time of data collection.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	105	105
Mean (Standard Error) [percent change]	-20.82 (1.48)	-11.91 (1.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	The endpoint was analysed using mixed model for repeated measures (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups were defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.91
	Confidence Interval	(2-Sided) 95%; -13.00 to -4.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1)
Description	The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score >1. Symptom-free day is defined as having daily total PSI of 0 on that day.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed. The data shown is therefore descriptive data.

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	23	15
Count of Participants [Participants]	15 14.3%	13 12.4%

9. Secondary Outcome

Title	PSI Total Score of 0 at Week 24
Description	The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score >1. Symptom-free day is defined as having daily total PSI of 0 on that day.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed. The data shown is therefore descriptive data.

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	23	15
Count of Participants [Participants]	5 4.8%	3 2.9%

10. Secondary Outcome

Title	Number of Symptom-free Days From Randomisation to Week 24
Description	The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score >1. Symptom-free day is defined as having daily total PSI of 0 on that day.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed.

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	64	33
Mean (Standard Deviation) [days]	0.44 (0.8)	0.42 (1.3)

11. Secondary Outcome

Title	Burden of Symptoms
Description	Burden of symptoms was assessed as the normalised area under the curve (AUC) of PSI from baseline to the last available assessment. The AUC for the PSI total score was calculated for each participant using the standard trapezoidal rule. The AUC was normalised by dividing it with the time from baseline to the last available assessment of the PSI total score. The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Not all participants had recorded PSI data, therefore the analysed number of participants is lower than the randomised number of participants.

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	83	78
Mean (Standard Error) [score on a scale]	6.00 (0.54)	10.92 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	The AUC was analysed using analysis of covariance (ANCOVA) with treatment group, baseline weight group, and the baseline PSI total score as explanatory variables. Treatment groups are defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.92
	Confidence Interval	(2-Sided) 95%; -6.31 to -3.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score
Description	DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The number of analysed participants is not the same as the number of randomised participants, as participants with missing data in all visits for a given endpoint are not included in the mixed model for repeated measurements (MMRM) analysis used to analyse the endpoint.

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	99	86
Mean (Standard Error) [score on a scale]	-16.67 (0.61)	-14.10 (0.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments	The endpoint is analysed by using mixed model for repeated measurements (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups are defined as randomised treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.57
	Confidence Interval	(2-Sided) 95%; -4.32 to -0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	DLQI Total Score of 0 or 1 at Week 24
Description	DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	105	105
Count of Participants [Participants]	70 66.7%	27 25.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments
	Type of Statistical Test	Superiority
	Comments	Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (<=100 kg, > 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	40.95
	Confidence Interval	(2-Sided) 95%; 28.75 to 53.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Other Pre-specified Outcome

Title	Change From Baseline at Week 24 in NAPSI Total Score
Description	The Nail Psoriasis Severity Index (NAPSI) grades nails by first dividing the nail area with imaginary horizontal and vertical lines into 4 quarters. The following 8 clinical features of nail psoriasis are then scored based on the number of quarters in which the feature is present (0 to 4) to arrive at a NAPSI score of 0 to 32 for each nail: Pitting. Leukonychia. Red spots in lunula. Nail plate crumbling. Oil drop (salmon patch) discoloration. Onycholysis. Nail bed hyperkeratosis. Splinter haemorrhages. A negative change in NAPSI score means that the NAPSI score was lower at the time of data collection.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Only participants with nail involvement at baseline were included in the analysis. Therefore the number of analysed participants differs from the number of randomised participants.

Arm/Group Title	Brodalumab	Fumaric Acid Esters
Arm/Group Description	Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks.	Oral fumaric acid esters up to 240 mg 3 times daily (TID).
Measure Participants	43	38
Mean (Standard Error) [score on a scale]	-2.97 (0.54)	-1.26 (0.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brodalumab, Fumaric Acid Esters
	Comments
	Type of Statistical Test	Superiority
	Comments	The endpoint was analysed by using mixed model for repeated measures (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups were defined as randomised treatment.
Statistical Test of Hypothesis	p-Value	0.028
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.72
	Confidence Interval	(2-Sided) 95%; -3.24 to -0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From the first day of investigational medicinal product (IMP) administration and until 32 weeks later for brodalumab and 26 weeks later for fumaric acid esters. The difference in collection periods was due to the different half-lives of the IMPs.
Arm/Group Title	Brodalumab 210 mg		Fumaric Acid Ester
Arm/Group Description	Kyntheum® (brodalumab) pre-filled syringe 210 mg/1.5 mL solution for subcutaneous injections. First 3 injections are administered weekly, and hereafter every two weeks (Q2W).		Fumaderm® initial dose tablets (30 mg dimethyl fumarate, 67 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt) > Fumaderm® tablets (120 mg dimethyl fumarate, 87 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt). Fumaderm® tablets are administered orally up to 3 times daily in accordance with the dosing scheme in the label.
All Cause Mortality
	Brodalumab 210 mg		Fumaric Acid Ester
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/104 (0%)		0/102 (0%)
Serious Adverse Events
	Brodalumab 210 mg		Fumaric Acid Ester
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/104 (2.9%)		1/102 (1%)
Gastrointestinal disorders
Crohn's disease	0/104 (0%)	0	1/102 (1%)	1
Reactive gastropathy	1/104 (1%)	1	0/102 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic	1/104 (1%)	1	0/102 (0%)	0
Skin and subcutaneous tissue disorders
Stasis dermatitis	1/104 (1%)	1	0/102 (0%)	0
Other (Not Including Serious) Adverse Events
	Brodalumab 210 mg		Fumaric Acid Ester
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/104 (63.5%)		90/102 (88.2%)
Blood and lymphatic system disorders
Lymphopenia	2/104 (1.9%)	3	14/102 (13.7%)	14
Gastrointestinal disorders
Abdominal pain	2/104 (1.9%)	2	11/102 (10.8%)	13
Abdominal pain upper	2/104 (1.9%)	2	28/102 (27.5%)	43
Diarrhoea	4/104 (3.8%)	4	59/102 (57.8%)	77
Nausea	6/104 (5.8%)	7	9/102 (8.8%)	13
General disorders
Fatigue	5/104 (4.8%)	6	6/102 (5.9%)	8
Infections and infestations
Viral upper respiratory tract infection	35/104 (33.7%)	41	21/102 (20.6%)	24
Injury, poisoning and procedural complications
Overdose	8/104 (7.7%)	8	0/102 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	9/104 (8.7%)	10	4/102 (3.9%)	4
Back pain	6/104 (5.8%)	6	1/102 (1%)	1
Nervous system disorders
Headache	13/104 (12.5%)	27	12/102 (11.8%)	19
Psychiatric disorders
Depressive symptom	5/104 (4.8%)	5	7/102 (6.9%)	7
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	6/104 (5.8%)	6	1/102 (1%)	1
Skin and subcutaneous tissue disorders
Pruritus	6/104 (5.8%)	6	2/102 (2%)	2
Vascular disorders
Flushing	0/104 (0%)	0	29/102 (28.4%)	40

Limitations/Caveats

Operational challenges with the ePRO diary device given to trial participants led to missing data at baseline and Week 24. This made the analyses of the secondary patient-reported endpoints PSI response rate and PSI total score of 0 or 1 impossible.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigators have agreed to refrain from publishing based on data from this trial until the multi-center publication containing data from all sites has been published (usually after approx. 18 months). After this, any publication by individual investigators must be reviewed by the sponsor prior to submission. Sponsor has the right to remove any commercially confidential information and/or delay the publication up to 4 months to allow time for activities protecting intellectual rights.