Efficacy, Safety and Immunogenicity of BI 695501 Versus Humira® in Patients With Moderate to Severe Chronic Plaque Psoriasis

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02850965
• Collaborator: (none)
• Enrollment: 318
• Locations: 54
• Arms: 2
• Actual Duration (Months): 17
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To evaluate the efficacy and to compare efficacy and safety of BI 695501 versus Humira in patients with moderate to severe chronic plaque psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: BI 695501; Drug: Humira	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 318 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy, Safety, and Immunogenicity of BI 695501 Versus Humira® in Patients With Moderate to Severe Chronic Plaque Psoriasis: A Randomized, Double-Blind, Parallel-Arm, Multiple-Dose, Active Comparator Trial
• Actual Study Start Date: Aug 17, 2016
• Actual Primary Completion Date: Jan 17, 2018
• Actual Study Completion Date: Jan 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 695501	Drug: BI 695501
Active Comparator: Humira	Drug: Humira

Outcome Measures

Primary Outcome Measures

1. The Percentage of Patients With at Least 75% Reduction in Psoriasis Area and Severity Index (PASI 75) Response at Week 16 [Week 16]

   The PASI tool provides numeric scoring for a patient's overall psoriasis disease state, ranging from 0 to 72. Head (h), trunk (t), upper extremities (u) and lower extremities (l) areas were assessed; correspond to 10, 30, 20, and 40% of the total body area, respectively. The signs of severity, erythema (E), induration (I) and desquamation (D) of lesions were assessed using a numeric scale of 0 to 4 where 0 was a complete lack of cutaneous involvement and 4 was the severest possible involvement. The area of psoriatic involvement of these areas (Ah, At, Au, and Al) was given a numerical value: 0 = no involvement, 1 = <10%, 2 = 10 to <30%, 3 = 30 to <50%, 4 = 50 to <70%, 5 = 70 to <90%, and 6 = 90 to 100% involvement. PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 0.4(El+Il+Dl)Al. Percentage = least squares means per treatment groups back transformed using inverse logit function.

Secondary Outcome Measures

1. The Percentage of Patients With a PASI 75 Response at Week 24 [Week 24]

   The PASI tool provides numeric scoring for a patient's overall psoriasis disease state, ranging from 0 to 72. Head (h), trunk (t), upper extremities (u) and lower extremities (l) areas were assessed; correspond to 10, 30, 20, and 40% of the total body area, respectively. The signs of severity, erythema (E), induration (I) and desquamation (D) of lesions were assessed using a numeric scale of 0 to 4 where 0 was a complete lack of cutaneous involvement and 4 was the severest possible involvement. The area of psoriatic involvement of these areas (Ah, At, Au, and Al) was given a numerical value: 0 = no involvement, 1 = <10%, 2 = 10 to <30%, 3 = 30 to <50%, 4 = 50 to <70%, 5 = 70 to <90%, and 6 = 90 to 100% involvement. PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 0.4(El+Il+Dl)Al. Percentage = least squares means per treatment groups back transformed using inverse logit function.

2. The Mean Percentage Improvement in PASI at Week 16 [Week 16]

   The PASI tool provides numeric scoring for a patient's overall psoriasis disease state, ranging from 0 to 72. Head (h), trunk (t), upper extremities (u) and lower extremities (l) areas were assessed; correspond to 10, 30, 20, and 40% of the total body area, respectively. The signs of severity, erythema (E), induration (I) and desquamation (D) of lesions were assessed using a numeric scale of 0 to 4 where 0 was a complete lack of cutaneous involvement and 4 was the severest possible involvement. The area of psoriatic involvement of these areas (Ah, At, Au, and Al) was given a numerical value: 0 = no involvement, 1 =<10%, 2 =10 to <30%, 3 =30 to <50%, 4 =50 to <70%, 5 =70 to <90%, and 6 =90 to 100% involvement. PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 0.4(El+Il+Dl)Al. Results based on PASI mean percentage improvement from Baseline after 16 weeks of treatment = overall mean + treatment group + Baseline PASI + prior exposure to a biological agent + random error.

3. The Percentage of Patients With a Static Physician's Global Assessment (sPGA) ≤1 (Clear or Almost Clear) at Week 16 [Week 16]

   The Static Physician's Global Assessment (sPGA) is a 5-point score ranging from 0 to 4, based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The assessment was considered "static", which referred to the patient's disease state at the time of the assessment, without comparison to any of the patient's previous disease states (dynamic), whether at Baseline or at a previous visit. A lower score indicated less body coverage, with 0 being clear, 1 being almost clear, and 4 being. Percentage = least squares means per treatment groups back transformed using inverse logit function.

4. The Percentage of Patients Achieving a Dermatology Life Quality Index (DLQI) of 0 or 1 at Week 16 [Week 16]

   The DLQI is a subject-administered, 10-question, that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. It has a 1-week recall period. Every item score ranges from 0 (not relevant/not at all) to 3 (very much). Question 7 is a "yes/no" question where "yes" is scored as 3. The DLQI total score was calculated by summing the scores of each question resulting in a range of 0 to 30 where 0-1 = no effect on subject's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on the subject's life. The higher the score, the more the quality of life is impaired. If the answer to 1 question in a domain was missing, that domain was treated as missing. If 2 or more questions were left unanswered (missing), DLQI total score was treated as missing. Percentage = least squares means per treatment groups back transformed using inverse logit function.

5. The Percentage of Patients With Drug-related Adverse Events (AEs) [From first drug administration until 10 weeks after last drug administration, up to 34 weeks.]

   The secondary safety endpoint was defined as the percentage of patients with drug-related adverse events (AEs).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Males and females aged >=18 to =<80 years who have a diagnosis of moderate to severe chronic plaque psoriasis (with or without psoriatic arthritis) for at least 6 months before the first administration of study drug (a self-reported diagnosis confirmed by the investigator is acceptable), and which has been stable for the last 2 months with no changes in morphology or significant flares at both Screening and Baseline (Randomization):

• involved body surface area (BSA) >= 10% and

• Psoriasis Area and Severity Index (PASI) score >= 12 and

• static Physician's Global Assessment (sPGA) score of >= 3.

• Participants of reproductive potential (childbearing potential ) must be willing and able to use highly effective methods of birth control per International Council for Harmonization (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly during the trial and for 6 months following completion or discontinuation from the trial medication.

• Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to admission to the trial.

• Patients who are candidates for systemic therapy.

Exclusion criteria:

• Active ongoing inflammatory diseases other than psoriasis that might confound trial evaluations according to investigator's judgment.

• Previous treatment with more than 1 biological agent, or adalimumab or adalimumab biosimilar. No prior biologic exposure within last 6 months of screening.

• Patients with a significant disease other than psoriasis and/or a significant uncontrolled disease (such as, but not limited to, nervous system, renal, hepatic, endocrine, hematological, autoimmune or gastrointestinal disorders).

• Major surgery performed within 12 weeks prior to randomization or planned within 6 months after screening, e.g., total hip replacement.

• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.

• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.

• Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s).

• Chronic alcohol or drug abuse

• Women who are pregnant, nursing, or who plan to become pregnant during the course of this study or within the period at least 6 months following completion or discontinuation from the trial.

• Forms of psoriasis (e.g., pustular, erythrodermic and guttate) other than chronic plaque psoriasis. Drug-induced psoriasis (i.e., new onset or current exacerbation from e.g., beta blockers or lithium).

• Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection or a positive HIV test at screening (per the investigator discretion and where mandated by local authorities).

• Known chronic or relevant acute tuberculosis; no evidence of active tuberculosis.

• Known clinically significant coronary artery disease, significant cardiac arrhythmias, moderate to severe congestive heart failure (New York Heart Association Classes III or

1. or interstitial lung disease observed on chest X-ray.

• History of a severe allergic reaction, anaphylactic reaction, or hypersensitivity to a previously used biological drug or its excipients.

• Positive serology for hepatitis B virus (HBV) or hepatitis C virus (HCV).

• Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit; patients who are expecting to receive any live/attenuated virus or bacterial vaccinations during the trial or up to 3 months after the last dose of trial drug.

• Any treatment (including biologic therapies) that, in the opinion of the investigator, may place the patient at unacceptable risk during the trial.

• Known active infection of any kind (excluding fungal infections of nail beds), any major episode of infection requiring hospitalization or treatment with intravenous (i.v.) anti infectives within 4 weeks of the Screening Visit

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times upper limit of normal (ULN) at Screening.

• Hemoglobin < 8.0 g/dL at Screening.

• Platelets < 100,000/µL at Screening.

• Leukocyte count < 4000/µL at Screening.

• Creatinine clearance < 60 mL/min/1.73 m2 at Screening.

• Patients with a history of any clinically significant adverse reaction to murine or chimeric proteins, or natural rubber and latex, including serious allergic reactions.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group, LLC	Anniston	Alabama	United States	36207
2	Alliance Dermatology and MOHS Center PC	Phoenix	Arizona	United States	85032
3	Southern California Dermatology Inc.	Santa Ana	California	United States	92701
4	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
5	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
6	New Horizon Research Center	Miami	Florida	United States	33175
7	Renstar Medical Research	Ocala	Florida	United States	34471
8	Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
9	Advanced Clinical Research	Boise	Idaho	United States	83642
10	Heartland Research Associates, LLC	Wichita	Kansas	United States	67207
11	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States	73112
12	Altoona Center for Clinical Research, P.C.	Duncansville	Pennsylvania	United States	16635
13	Medical Research South	Charleston	South Carolina	United States	29407
14	Menter Dermatology Research Institute	Dallas	Texas	United States	75246
15	Dorothea	Chomutov		Czechia	43004
16	MU Dr. Helena Korandova s.r.o., Olomouc-Povel	Olomouc-Povel		Czechia	779 00
17	University Hospital Ostrava	Ostrava		Czechia	708 52
18	HOMEA spol. s.r.o., Pardubice	Pardubice		Czechia	530 02
19	Univ. Hospital Kralovske Vinohrady	Praha		Czechia	100 34
20	MU Dr. Jaroslav Dragon, Ústí nad Labem	Ústí nad Labem		Czechia	400 10
21	Center for Clinical and Basic Research, Tallinn	Tallinn		Estonia	10128
22	Hospital of South-Estonia Ltd, Võru Maakond	Võru Maakond		Estonia	65526
23	Rothhaar Studien GmbH	Berlin		Germany	10783
24	Rosenparkklinik GmbH, Darmstadt	Darmstadt		Germany	64283
25	Universitätsklinikum Carl Gustav Carus Dresden	Dresden		Germany	01307
26	Gemeinschaftspraxis Dr. Bräu Dr. Gross, Gießen	Gießen		Germany	35390
27	TFS Trial Form Support GmbH	Hamburg		Germany	20354
28	NZOZ Specderm, Bialystok	Bialystok		Poland	15-017
29	ClinicMed Badurski i wspolnicy Spolka Jawna, Bialystok	Bialystok		Poland	15-879
30	NSZOZ Unica CR, Dabrowka	Dabrowka		Poland	62-069
31	Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk	Gdansk		Poland	80-382
32	University Clinical Center, Gdansk	Gdansk		Poland	80-952
33	Synexus Polska Sp. z o.o. Oddzial w Gdyni, Gdynia	Gdynia		Poland	81-384
34	Synexus Polska Sp. z o.o. Oddzial w Katowicach, Katowice	Katowice		Poland	40-040
35	SOLUMED Centrum Medyczne, Poznan	Poznan		Poland	60-529
36	Laser Clin. S.C. Dr T. Kochanowski Dr A. Krolicki, Szczecin	Szczecin		Poland	70-332
37	Synexus Polska Sp. z o.o. Oddzial w Warszawie, Warszawa	Warszawa		Poland	01-192
38	Synexus Polska Sp. z o.o. Oddzial we Wroclawiu, Wroclaw	Wroclaw		Poland	50-088
39	State Medical University, Kazan	Kazan		Russian Federation	420012
40	Dermatovenereological Dispensary #10, St. Petersburg	Saint-Petersburg		Russian Federation	194021
41	ArsVitae NorthWest LLC	Saint-Petersburg		Russian Federation	194223
42	1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.	Saint-Petersburg		Russian Federation	197022
43	Smolensk State Medical University, Smolensk	Smolensk		Russian Federation	214019
44	LLC Skin Disease Clinic of Pier Volkenstein, St. Petersburg	St. Petersburg		Russian Federation	190123
45	EKO-Bezopasnost, St. Petersburg	St. Petersburg		Russian Federation	196143
46	Institution of Healthcare "Nikolaevskaya Hospital"	St. Petersburg		Russian Federation	198510
47	Faculty hospital with clinics F.D. Roosevelta	Banska Bystrica		Slovakia	97409
48	Dermatovenerologicke oddelenie sanatorneho typu, Svidnik	Svidnik		Slovakia	089 01
49	Territorial Medical Association Dermatovenerology, Kyiv	Kyiv		Ukraine	01032
50	CH of State Border Service of Ukraine, Lviv	Lviv		Ukraine	79014
51	CI Odesa Regional Dermatovenerologic Dispensary, Odesa	Odesa		Ukraine	65006
52	CI RC Dermatovenerologic Dispensary, Ivano-Frankivsk	Saint Ivano-Frankivsk		Ukraine	76018
53	SI Ternopil Regional Dermatovenerologic Dispensary, Ternopil	Ternopil		Ukraine	46006
54	MCIC MC LLC Health Clinic, Vinnytsia	Vinnytsia		Ukraine	21029

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Study Protocol - Apr 26, 2016
• Statistical Analysis Plan - Jan 31, 2018

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02850965
• Other Study ID Numbers: 1297.12; 2016-000613-79
• First Posted: Aug 1, 2016
• Last Update Posted: Feb 8, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Psoriasis; Adalimumab

Study Results

Participant Flow

Recruitment Details	This was a Phase III, multinational, randomized, double-blind, parallel-arm, multiple-dose, active-comparator trial of BI 695501 and US-licensed Humira with a 24-week treatment period and 10 weeks of safety follow up, in patients with moderate to severe chronic plaque psoriasis.
Pre-assignment Detail	All patients were screened for eligibility to participate in the trial. Patients attended specialist sites to ensure that all patients met all inclusion/exclusion criteria. Patients were not to be entered to trial treatment if any one of the specific entry criteria were not met.

Arm/Group Title	BI 695501	US-licensed Humira
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.	Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.
Period Title: Overall Study
STARTED	159	159
Treated	159	158
COMPLETED	141	134
NOT COMPLETED	18	25

Baseline Characteristics

Arm/Group Title	BI 695501	US-licensed Humira	Total
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.	Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.	Total of all reporting groups
Overall Participants	159	158	317
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.1 (12.79)	44.7 (13.92)	43.4 (13.41)
Sex: Female, Male (Count of Participants)
Female	58 36.5%	56 35.4%	114 36%
Male	101 63.5%	102 64.6%	203 64%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 7.5%	10 6.3%	22 6.9%
Not Hispanic or Latino	147 92.5%	146 92.4%	293 92.4%
Unknown or Not Reported	0 0%	2 1.3%	2 0.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.6%	1 0.3%
Black or African American	1 0.6%	1 0.6%	2 0.6%
White	157 98.7%	156 98.7%	313 98.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 0.6%	0 0%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Patients With at Least 75% Reduction in Psoriasis Area and Severity Index (PASI 75) Response at Week 16
Description	The PASI tool provides numeric scoring for a patient's overall psoriasis disease state, ranging from 0 to 72. Head (h), trunk (t), upper extremities (u) and lower extremities (l) areas were assessed; correspond to 10, 30, 20, and 40% of the total body area, respectively. The signs of severity, erythema (E), induration (I) and desquamation (D) of lesions were assessed using a numeric scale of 0 to 4 where 0 was a complete lack of cutaneous involvement and 4 was the severest possible involvement. The area of psoriatic involvement of these areas (Ah, At, Au, and Al) was given a numerical value: 0 = no involvement, 1 = <10%, 2 = 10 to <30%, 3 = 30 to <50%, 4 = 50 to <70%, 5 = 70 to <90%, and 6 = 90 to 100% involvement. PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 0.4(El+Il+Dl)Al. Percentage = least squares means per treatment groups back transformed using inverse logit function.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS contained all randomized patients who received at least one dose of trial medication, and had all efficacy measures relevant for the PASI 75, measured at baseline and at least once post-baseline (prior to or on Week 16).

Arm/Group Title	BI 695501	US-licensed Humira
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.	Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.
Measure Participants	158	157
Number [Percentage (%)]	68.2	70.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 695501, US-licensed Humira
	Comments	The week 16 confidence interval for the estimated difference in percentage are produced using the cumulative distribution function method of Reeve.
	Type of Statistical Test	Equivalence
	Comments	Protocol defined margins are: [-18.0%, +18.0%] for Week 16, 95% confidence interval. Between-imputation variance is zero. Confidence interval is based on one imputed set.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in PASI 75 Response Rate
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -14.4 to 8.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in PASI 75 Response Rate = (BI 695501 - US-licensed Humira, %).
Other Statistical Analysis		The statistical model: Logit (response to treatment at Week 16)=Treatment+Baseline PASI+Prior exposure to a biologic agent+random error. Model included fixed, categorical effects of treatment (BI 695501 vs US-licensed Humira) and prior exposure to a biologic agent (yes/no), continuous effect of baseline PASI. The random error was assumed to be binomially distributed.

2. Secondary Outcome

Title	The Percentage of Patients With a PASI 75 Response at Week 24
Description	The PASI tool provides numeric scoring for a patient's overall psoriasis disease state, ranging from 0 to 72. Head (h), trunk (t), upper extremities (u) and lower extremities (l) areas were assessed; correspond to 10, 30, 20, and 40% of the total body area, respectively. The signs of severity, erythema (E), induration (I) and desquamation (D) of lesions were assessed using a numeric scale of 0 to 4 where 0 was a complete lack of cutaneous involvement and 4 was the severest possible involvement. The area of psoriatic involvement of these areas (Ah, At, Au, and Al) was given a numerical value: 0 = no involvement, 1 = <10%, 2 = 10 to <30%, 3 = 30 to <50%, 4 = 50 to <70%, 5 = 70 to <90%, and 6 = 90 to 100% involvement. PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 0.4(El+Il+Dl)Al. Percentage = least squares means per treatment groups back transformed using inverse logit function.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	BI 695501	US-licensed Humira
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.	Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.
Measure Participants	158	157
Number [Percentage (%)]	75.3	72.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 695501, US-licensed Humira
	Comments	The week 24 confidence interval for the estimated difference in percentage are produced using the cumulative distribution function method of Reeve.
	Type of Statistical Test	Other
	Comments	Missing PASI 75 at Week 24 data were imputed using a combination of non-responder imputation (NRI) and last observed carried forward (LOCF).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in PASI 75 Response Rate
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; -8.5 to 12.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in PASI 75 Response Rate = (BI 695501 - US-licensed Humira, %).
Other Statistical Analysis		The statistical model: Logit (response to treatment at Week 24)=Treatment+Baseline PASI+Prior exposure to a biologic agent+random error. Model included fixed, categorical effects of treatment (BI 695501 vs US-licensed Humira) and prior exposure to a biologic agent (yes/no), continuous effect of baseline PASI. The random error was assumed to be binomially distributed.

3. Secondary Outcome

Title	The Mean Percentage Improvement in PASI at Week 16
Description	The PASI tool provides numeric scoring for a patient's overall psoriasis disease state, ranging from 0 to 72. Head (h), trunk (t), upper extremities (u) and lower extremities (l) areas were assessed; correspond to 10, 30, 20, and 40% of the total body area, respectively. The signs of severity, erythema (E), induration (I) and desquamation (D) of lesions were assessed using a numeric scale of 0 to 4 where 0 was a complete lack of cutaneous involvement and 4 was the severest possible involvement. The area of psoriatic involvement of these areas (Ah, At, Au, and Al) was given a numerical value: 0 = no involvement, 1 =<10%, 2 =10 to <30%, 3 =30 to <50%, 4 =50 to <70%, 5 =70 to <90%, and 6 =90 to 100% involvement. PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 0.4(El+Il+Dl)Al. Results based on PASI mean percentage improvement from Baseline after 16 weeks of treatment = overall mean + treatment group + Baseline PASI + prior exposure to a biological agent + random error.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	BI 695501	US-licensed Humira
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.	Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.
Measure Participants	149	149
Least Squares Mean (95% Confidence Interval) [Percentage (%)]	83.7	82.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 695501, US-licensed Humira
	Comments	Analysis of covariance (ANCOVA) was performed based on the following model: PASI percentage improvement from baseline at Week 16= Treatment + Baseline PASI +Prior exposure to a biologic agent + random error.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Squares Means
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; -2.7 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference of Least Squares Means (LSM)= LSM of (BI 695501 - Humira)

4. Secondary Outcome

Title	The Percentage of Patients With a Static Physician's Global Assessment (sPGA) ≤1 (Clear or Almost Clear) at Week 16
Description	The Static Physician's Global Assessment (sPGA) is a 5-point score ranging from 0 to 4, based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The assessment was considered "static", which referred to the patient's disease state at the time of the assessment, without comparison to any of the patient's previous disease states (dynamic), whether at Baseline or at a previous visit. A lower score indicated less body coverage, with 0 being clear, 1 being almost clear, and 4 being. Percentage = least squares means per treatment groups back transformed using inverse logit function.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	BI 695501	US-licensed Humira
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.	Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.
Measure Participants	158	157
Number [Percentage (%)]	59.6	52.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 695501, US-licensed Humira
	Comments	The week 16 confidence interval for the estimated difference in percentage are produced using the cumulative distribution function method of Reeve.
	Type of Statistical Test	Other
	Comments	Missing sPGA at Week 16 data were imputed using a combination of non-responder imputation (NRI) and last observed carried forward (LOCF).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in sPGA <= 1 Response Rate
	Estimated Value	7.5
	Confidence Interval	(2-Sided) 95%; -4.8 to 19.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in sPGA <= 1 Response Rate = (BI 695501 - US-licensed Humira, %)
Other Statistical Analysis		The statistical model: Logit (response to treatment at Week 16)=Treatment+Baseline PASI+Prior exposure to a biologic agent+random error. Model included fixed, categorical effects of treatment (BI 695501 vs US-licensed Humira) and prior exposure to a biologic agent (yes/no), continuous effect of baseline PASI.

5. Secondary Outcome

Title	The Percentage of Patients Achieving a Dermatology Life Quality Index (DLQI) of 0 or 1 at Week 16
Description	The DLQI is a subject-administered, 10-question, that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. It has a 1-week recall period. Every item score ranges from 0 (not relevant/not at all) to 3 (very much). Question 7 is a "yes/no" question where "yes" is scored as 3. The DLQI total score was calculated by summing the scores of each question resulting in a range of 0 to 30 where 0-1 = no effect on subject's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on the subject's life. The higher the score, the more the quality of life is impaired. If the answer to 1 question in a domain was missing, that domain was treated as missing. If 2 or more questions were left unanswered (missing), DLQI total score was treated as missing. Percentage = least squares means per treatment groups back transformed using inverse logit function.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	BI 695501	US-licensed Humira
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.	Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.
Measure Participants	158	157
Number [Percentage (%)]	67.2	66.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 695501, US-licensed Humira
	Comments	The week 16 confidence interval for the estimated difference in percentage are produced using the cumulative distribution function method of Reeve.
	Type of Statistical Test	Other
	Comments	Missing DLQI at Week 16 data were imputed using a combination of non-responder imputation (NRI) and last observed carried forward (LOCF).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in DLQI Response Rate
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -11.7 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in DLQI (0, 1) Response Rate = (BI 695501 - US-licensed Humira, %)
Other Statistical Analysis		The statistical model: Logit (response to treatment at Week 16)=Treatment+Baseline PASI+Prior exposure to a biologic agent+random error. Model included fixed, categorical effects of treatment (BI 695501 vs US-licensed Humira) and prior exposure to a biologic agent (yes/no), continuous effect of baseline PASI.

6. Secondary Outcome

Title	The Percentage of Patients With Drug-related Adverse Events (AEs)
Description	The secondary safety endpoint was defined as the percentage of patients with drug-related adverse events (AEs).
Time Frame	From first drug administration until 10 weeks after last drug administration, up to 34 weeks.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAF): The SAF contained all patients who provided signed informed consent, who were randomized, and who received at least one dose of trial medication.

Arm/Group Title	BI 695501	US-licensed Humira
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.	Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.
Measure Participants	159	158
Number [Percentage of patients (%)]	13.2	20.3

Adverse Events

Time Frame	From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Arm/Group Title	BI 695501		US-licensed Humira
Arm/Group Description	Patients were administered with BI 695501 via subcutaneous (SC) injection 80 milligram (mg) on Day 1 and 40 milligram (mg) on every other week from Week 1 to Week 23.		Patients were administered US-licensed Humira via subcutaneous (SC) injection 80 mg on Day 1 and 40 milligram on every other week from Week 1 to Week 23.
All Cause Mortality
	BI 695501		US-licensed Humira
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/159 (0%)		0/158 (0%)
Serious Adverse Events
	BI 695501		US-licensed Humira
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/159 (3.1%)		7/158 (4.4%)
Cardiac disorders
Congestive cardiomyopathy	1/159 (0.6%)		0/158 (0%)
Pericarditis	0/159 (0%)		1/158 (0.6%)
Gastrointestinal disorders
Pancreatitis chronic	0/159 (0%)		1/158 (0.6%)
Hepatobiliary disorders
Hepatitis toxic	0/159 (0%)		1/158 (0.6%)
Infections and infestations
Abdominal abscess	1/159 (0.6%)		0/158 (0%)
Furuncle	0/159 (0%)		1/158 (0.6%)
Kidney infection	0/159 (0%)		1/158 (0.6%)
Oral herpes	1/159 (0.6%)		0/158 (0%)
Orchitis	0/159 (0%)		1/158 (0.6%)
Upper respiratory tract infection	1/159 (0.6%)		0/158 (0%)
Musculoskeletal and connective tissue disorders
Exostosis	0/159 (0%)		1/158 (0.6%)
Foot deformity	0/159 (0%)		1/158 (0.6%)
Nervous system disorders
Transient ischaemic attack	0/159 (0%)		1/158 (0.6%)
Renal and urinary disorders
Renal colic	0/159 (0%)		1/158 (0.6%)
Skin and subcutaneous tissue disorders
Psoriasis	1/159 (0.6%)		0/158 (0%)
Other (Not Including Serious) Adverse Events
	BI 695501		US-licensed Humira
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/159 (10.7%)		24/158 (15.2%)
General disorders
Injection site erythema	5/159 (3.1%)		10/158 (6.3%)
Injection site pain	3/159 (1.9%)		10/158 (6.3%)
Infections and infestations
Nasopharyngitis	12/159 (7.5%)		7/158 (4.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.