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

Psoriasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02850965
• Other study ID #: 1297.12
• Secondary ID: 2016-000613-79
• Status: Completed
• Phase: Phase 3
• Start date: August 17, 2016
• Est. completion date: January 17, 2018

Study information

• Verified date: January 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: January 17, 2018
• Est. primary completion date: January 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 IV) 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.

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• BI 695501

• Humira

Locations

Country	Name	City	State
Czechia	Dorothea	Chomutov
Czechia	MU Dr. Helena Korandova s.r.o., Olomouc-Povel	Olomouc-Povel
Czechia	University Hospital Ostrava	Ostrava
Czechia	HOMEA spol. s.r.o., Pardubice	Pardubice
Czechia	Univ. Hospital Kralovske Vinohrady	Praha
Czechia	MU Dr. Jaroslav Dragon, Ústí nad Labem	Ústí nad Labem
Estonia	Center for Clinical and Basic Research, Tallinn	Tallinn
Estonia	Hospital of South-Estonia Ltd, Võru Maakond	Võru Maakond
Germany	Rothhaar Studien GmbH	Berlin
Germany	Rosenparkklinik GmbH, Darmstadt	Darmstadt
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Gemeinschaftspraxis Dr. Bräu Dr. Gross, Gießen	Gießen
Germany	TFS Trial Form Support GmbH	Hamburg
Poland	ClinicMed Badurski i wspolnicy Spolka Jawna, Bialystok	Bialystok
Poland	NZOZ Specderm, Bialystok	Bialystok
Poland	NSZOZ Unica CR, Dabrowka	Dabrowka
Poland	Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk	Gdansk
Poland	University Clinical Center, Gdansk	Gdansk
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdyni, Gdynia	Gdynia
Poland	Synexus Polska Sp. z o.o. Oddzial w Katowicach, Katowice	Katowice
Poland	SOLUMED Centrum Medyczne, Poznan	Poznan
Poland	Laser Clin. S.C. Dr T. Kochanowski Dr A. Krolicki, Szczecin	Szczecin
Poland	Synexus Polska Sp. z o.o. Oddzial w Warszawie, Warszawa	Warszawa
Poland	Synexus Polska Sp. z o.o. Oddzial we Wroclawiu, Wroclaw	Wroclaw
Russian Federation	State Medical University, Kazan	Kazan
Russian Federation	1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.	Saint-Petersburg
Russian Federation	ArsVitae NorthWest LLC	Saint-Petersburg
Russian Federation	Dermatovenereological Dispensary #10, St. Petersburg	Saint-Petersburg
Russian Federation	Smolensk State Medical University, Smolensk	Smolensk
Russian Federation	EKO-Bezopasnost, St. Petersburg	St. Petersburg
Russian Federation	Institution of Healthcare "Nikolaevskaya Hospital"	St. Petersburg
Russian Federation	LLC Skin Disease Clinic of Pier Volkenstein, St. Petersburg	St. Petersburg
Slovakia	Faculty hospital with clinics F.D. Roosevelta	Banska Bystrica
Slovakia	Dermatovenerologicke oddelenie sanatorneho typu, Svidnik	Svidnik
Ukraine	Territorial Medical Association Dermatovenerology, Kyiv	Kyiv
Ukraine	CH of State Border Service of Ukraine, Lviv	Lviv
Ukraine	CI Odesa Regional Dermatovenerologic Dispensary, Odesa	Odesa
Ukraine	CI RC Dermatovenerologic Dispensary, Ivano-Frankivsk	Saint Ivano-Frankivsk
Ukraine	SI Ternopil Regional Dermatovenerologic Dispensary, Ternopil	Ternopil
Ukraine	MCIC MC LLC Health Clinic, Vinnytsia	Vinnytsia
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	Advanced Clinical Research	Boise	Idaho
United States	Medical Research South	Charleston	South Carolina
United States	Menter Dermatology Research Institute	Dallas	Texas
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Altoona Center for Clinical Research, P.C.	Duncansville	Pennsylvania
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	New Horizon Research Center	Miami	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Alliance Dermatology and MOHS Center PC	Phoenix	Arizona
United States	Southern California Dermatology Inc.	Santa Ana	California
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	Heartland Research Associates, LLC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Czechia,  Estonia,  Germany,  Poland,  Russian Federation,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage of Patients With at Least 75% Reduction in Psoriasis Area and Severity Index (PASI 75) Response at 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.	Week 16
Secondary	The Percentage of Patients With a PASI 75 Response at 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.	Week 24
Secondary	The Mean Percentage Improvement in PASI at 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.	Week 16
Secondary	The Percentage of Patients With a Static Physician's Global Assessment (sPGA) =1 (Clear or Almost Clear) at 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.	Week 16
Secondary	The Percentage of Patients Achieving a Dermatology Life Quality Index (DLQI) of 0 or 1 at 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.	Week 16
Secondary	The Percentage of Patients With Drug-related Adverse Events (AEs)	The secondary safety endpoint was defined as 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.

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