Trial Outcomes & Findings for Efficacy, Safety and Immunogenicity of BI 695501 Versus Humira® in Patients With Moderate to Severe Chronic Plaque Psoriasis (NCT NCT02850965)

Last Updated: 2019-02-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

318 participants

Primary outcome timeframe

Week 16

Results posted on

2019-02-08

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	BI 695501 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.	US-licensed Humira 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.
Overall Study STARTED	159	159
Overall Study Treated	159	158
Overall Study COMPLETED	141	134
Overall Study NOT COMPLETED	18	25

Reasons for withdrawal

Reasons for withdrawal
Measure	BI 695501 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.	US-licensed Humira 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.
Overall Study Other than listed	3	4
Overall Study Protocol Violation	0	2
Overall Study Lost to Follow-up	5	3
Overall Study Lack of Efficacy	4	8
Overall Study Adverse Event	3	2
Overall Study Withdrawal by Subject	3	4
Overall Study Physician Decision	0	1
Overall Study Randomized but not treated	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI 695501 n=159 Participants 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.	US-licensed Humira n=158 Participants 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 n=317 Participants Total of all reporting groups
Age, Continuous	42.1 Years STANDARD_DEVIATION 12.79 • n=5 Participants	44.7 Years STANDARD_DEVIATION 13.92 • n=7 Participants	43.4 Years STANDARD_DEVIATION 13.41 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	56 Participants n=7 Participants	114 Participants n=5 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	102 Participants n=7 Participants	203 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	147 Participants n=5 Participants	146 Participants n=7 Participants	293 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	157 Participants n=5 Participants	156 Participants n=7 Participants	313 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 16

Population: 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).

Outcome measures

Outcome measures
Measure	BI 695501 n=158 Participants 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.	US-licensed Humira n=157 Participants 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.
The Percentage of Patients With at Least 75% Reduction in Psoriasis Area and Severity Index (PASI 75) Response at Week 16	68.2 Percentage (%)	70.4 Percentage (%)

SECONDARY outcome

Timeframe: Week 24

Population: FAS

Outcome measures

Outcome measures
Measure	BI 695501 n=158 Participants 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.	US-licensed Humira n=157 Participants 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.
The Percentage of Patients With a PASI 75 Response at Week 24	75.3 Percentage (%)	72.4 Percentage (%)

SECONDARY outcome

Timeframe: Week 16

Population: FAS

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.

Outcome measures

Outcome measures
Measure	BI 695501 n=149 Participants 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.	US-licensed Humira n=149 Participants 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.
The Mean Percentage Improvement in PASI at Week 16	83.7 Percentage (%) Interval 80.2 to 87.2	82.1 Percentage (%) Interval 78.6 to 85.6

SECONDARY outcome

Timeframe: Week 16

Population: FAS

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.

Outcome measures

Outcome measures
Measure	BI 695501 n=158 Participants 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.	US-licensed Humira n=157 Participants 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.
The Percentage of Patients With a Static Physician's Global Assessment (sPGA) ≤1 (Clear or Almost Clear) at Week 16	59.6 Percentage (%)	52.1 Percentage (%)

SECONDARY outcome

Timeframe: Week 16

Population: FAS

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.

Outcome measures

Outcome measures
Measure	BI 695501 n=158 Participants 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.	US-licensed Humira n=157 Participants 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.
The Percentage of Patients Achieving a Dermatology Life Quality Index (DLQI) of 0 or 1 at Week 16	67.2 Percentage (%)	66.8 Percentage (%)

SECONDARY outcome

Timeframe: From first drug administration until 10 weeks after last drug administration, up to 34 weeks.

Population: 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.

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

Outcome measures

Outcome measures
Measure	BI 695501 n=159 Participants 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.	US-licensed Humira n=158 Participants 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.
The Percentage of Patients With Drug-related Adverse Events (AEs)	13.2 Percentage of patients (%)	20.3 Percentage of patients (%)

Adverse Events

BI 695501

Serious events: 5 serious events

Other events: 17 other events

Deaths: 0 deaths

US-licensed Humira

Serious events: 7 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	BI 695501 n=159 participants at risk 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.	US-licensed Humira n=158 participants at risk 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.
Infections and infestations Nasopharyngitis	7.5% 12/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	4.4% 7/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
General disorders Injection site erythema	3.1% 5/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	6.3% 10/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
General disorders Injection site pain	1.9% 3/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	6.3% 10/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.

Additional Information

Boehringer Ingelheim, Call Centre

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	BI 695501 n=159 participants at risk 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.	US-licensed Humira n=158 participants at risk 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.
Infections and infestations Abdominal abscess	0.63% 1/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.00% 0/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Infections and infestations Furuncle	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Infections and infestations Kidney infection	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Infections and infestations Oral herpes	0.63% 1/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.00% 0/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Infections and infestations Orchitis	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Infections and infestations Upper respiratory tract infection	0.63% 1/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.00% 0/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Nervous system disorders Transient ischaemic attack	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Cardiac disorders Congestive cardiomyopathy	0.63% 1/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.00% 0/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Cardiac disorders Pericarditis	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Gastrointestinal disorders Pancreatitis chronic	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Hepatobiliary disorders Hepatitis toxic	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Skin and subcutaneous tissue disorders Psoriasis	0.63% 1/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.00% 0/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Musculoskeletal and connective tissue disorders Exostosis	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.
Renal and urinary disorders Renal colic	0.00% 0/159 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.	0.63% 1/158 • From first drug administration until 10 weeks after last drug administration, up to 33 weeks.