Clinical trial NCT03210259: The VOLTAIRE-X Trial Looks at the Effect of Switching Between Humira® and BI 695501 in Patients With Plaque Psoriasis
Official title: VOLTAIRE-X: Pharmacokinetics, Safety, Immunogenicity and Efficacy 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriasis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-07-06
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the trial is to assess the PK similarity between patients receiving Humira® continuously vs those who alternate between BI 695501 and Humira®, in patients with moderate-to-severe chronic plaque psoriasis.

The secondary objectives of this trial are to descriptively compare the safety, immunogenicity and efficacy profiles between patients receiving Humira® continuously vs those who alternate between BI 695501 and Humira®.


Eligibility criteria: Inclusion criteria

* Males and females aged ≥ 18 to \< 80 years at screening 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 trial drug (a self-reported diagnosis confirmed by the Investigator is acceptable), and which has been stable per Investigator opinion for the last 2 months with no changes in morphology or significant flares at both screening and baseline:

  * involved body surface area (BSA) ≥ 10% and
  * PASI score ≥ 12 and
  * sPGA score of ≥ 3.
* Participants of reproductive potential (childbearing potential1) must be willing and able to use highly effective methods of birth control per International Council for Harmonisation (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. A list of contraception methods meeting these criteria is provided in patient information.
* 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 or phototherapy according to Investigator judgement.

Exclusion criteria

* Active ongoing inflammatory diseases other than psoriasis that might confound trial evaluations according to Investigator's judgment.
* Prior exposure to any biologic therapies for any auto-immune diseases (eg: RA, Psoriasis, Crohns Disease, etc).
* 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). A significant disease is defined as a disease which, in the opinion of the Investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.
* Major surgery (major according to the Investigator's assessment) performed within 12 weeks before enrollment 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 (in the opinion of the Investigator) 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 trial, or less than 30 days (or less than 5 half-lives, whichever is longer) since ending another investigational device or drug trial(s), or receiving other investigational treatment(s).
* Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion, makes the patient an unreliable trial subject or unlikely to complete the trial.
* Women who are pregnant, nursing, or who plan to become pregnant during the course of this trial or within the period at least 6 months following completion or discontinuation from the trial medication.
* 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 TB; IGRA TB test or PPD skin test will be performed according to the labelling for Humira®. If the result is positive, patients may participate in the trial if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active TB. If latent TB is confirmed, then treatment must have been initiated before treatment in the study and continued according to local country guidelines.
* Known clinically significant (per Investigator opinion) 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.
* Patients with a history of any clinically significant adverse reaction (including serious allergic reactions, or anaphylactic reaction, or hypersensitivity) to murine or chimeric proteins, previously used biological drug or its excipients, or natural rubber and latex.
* Positive serology for HBV or 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 hospitalisation or treatment with intravenous (i.v.) antiinfectives within 4 weeks of the Screening Visit or completion of oral anti-infectives within 2 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.
* Calculated creatinine clearance \< 60 mL/min at screening.

Primary outcomes:
measure: Area Under the Plasma Concentration Time Curve Over the Dosing Interval of Week 30 to 32 (AUCτ, 30-32) for Adalimumab in Plasma
timeFrame: Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.
measure: Maximum Observed Concentration During the Dosing Interval Week 30-32 (Cmax, 30-32) for Adalimumab in Plasma
timeFrame: Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.
Secondary outcomes:
measure: Minimum Observed Concentration During the Dosing Interval of Week 30 to 32 (Cmin, 30-32) for Adalimumab in Plasma
timeFrame: Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.
measure: Time to Maximum Observed Concentration During the Dosing Interval of Week 30 to 32 (Tmax, 30-32) for Adalimumab in Plasma
timeFrame: Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.
measure: Percentage of Patients With a 75% Reduction in Psoriasis Area and Severity Index (PASI75) Response at Week 32
timeFrame: At week 32
measure: Percentage of Patients With a Static Physician's Global Assessment (sPGA) Score ≤ 1 (Clear or Almost Clear) at Week 32
timeFrame: At week 32
measure: Number of Patients With Anti-drug Antibody (ADA) to Adalimumab at Week 32
timeFrame: Immunogenicity samples were collected pre-dose at Week 32.
measure: Number of Patients With Neutralizing Antibody (nAb) to Adalimumab at Week 32
timeFrame: Immunogenicity samples were collected pre-dose at Week 32.
measure: Anti-drug Antibody (ADA) Titer of Patients With ADA at Week 32
timeFrame: Immunogenicity samples were collected pre-dose at Week 32.
measure: Neutralizing Anti-drug Antibody (nAb) Titer of Patients With nAb at Week 32
timeFrame: Immunogenicity samples were collected pre-dose at Week 32.
measure: Percentage of Patients With Drug-related Adverse Events (AEs) During the Post-Randomization Period
timeFrame: From first dose of trial post-randomization medication until 10 weeks after last dose of trial post-randomization medication, up to 44 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Total Skin and Beauty Dermatology Center, PC
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Encinitas
country: United States
facility: California Dermatology & Clinical Research Institute
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Sherman Oaks
country: United States
facility: Shahram Jacobs MD, Inc./Unison Clinical Trials
state: California
city: Hialeah
country: United States
facility: Universal Clinical Research
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Overland Park
country: United States
facility: Kansas City Dermatology, PA
state: Kansas
city: Bay City
country: United States
facility: Great Lakes Research Group, Inc.
state: Michigan
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: High Point
country: United States
facility: Dermatology Consulting Services
state: North Carolina
city: Johnston
country: United States
facility: Clinical Partners, LLC
state: Rhode Island
city: Fountain Inn
country: United States
facility: Palmetto Clinical Trial Services, LLC
state: South Carolina
city: Arlington
country: United States
facility: Arlington Research Center
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
city: Berlin
country: Germany
facility: Rothhaar Studien GmbH
city: Dresden
country: Germany
facility: Klinische Forschung Dresden, GmbH
city: Budapest
country: Hungary
facility: UNO Medical Trials Kft.
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Univ.teach.Hosp
city: Szolnok
country: Hungary
facility: ALLERGO-DERM BAKOS Kft.
city: Riga
country: Latvia
facility: Riga 1st Hosp, Out-patient Department
city: Riga
country: Latvia
facility: Derma Clinic Riga Ltd
city: Riga
country: Latvia
facility: Health Center 4, Affiliate Diagnostic Center
city: Riga
country: Latvia
facility: J. Kisis Ltd
city: Talsi
country: Latvia
facility: Smite Aija practice in dermatology and venerology
city: Ventspils
country: Latvia
facility: Outpatient Clinic of Ventspils
city: Gdansk
country: Poland
facility: Poradnia Kardiologiczna Jaroslaw Jurowiecki
city: Gdansk
country: Poland
facility: Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk
city: Gdynia
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Gdyni, Gdynia
city: Krakow
country: Poland
facility: Malopolskie medical center S.C, Krakow
city: Lodz
country: Poland
facility: SANTA FAMILIA Centrum Badan, Profilaktyki i Leczenia
city: Lodz
country: Poland
facility: Dermoklinika medical center, Lodz
city: Oswiecim
country: Poland
facility: Medicome Sp. z o.o.
city: Skierniewice
country: Poland
facility: Clinmedica Research Omc sp. z o.o. sp.k., Skierniewice
city: Szczecin
country: Poland
facility: Laser Clin. S.C. Dr T. Kochanowski Dr A. Krolicki, Szczecin
city: Warszawa
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Warszawie, Warszawa
city: Saint-Petersburg
country: Russian Federation
facility: LLC "Alliance Biomedical - Russian Group"
city: St. Petersburg
country: Russian Federation
facility: EKO-Bezopasnost, St. Petersburg
city: St. Petersburg
country: Russian Federation
facility: Institution of Healthcare "Nikolaevskaya Hospital"
city: Dnipro
country: Ukraine
facility: SI Road Clinical Hospital of DS of SE PZ Dept of Dermatovenerology SI DMA of MOHU
city: Kherson
country: Ukraine
facility: Kherson clin.hosp.Afanasiia&Olhy Tropinykh
city: Uzhgorod
country: Ukraine
facility: Treatment - Diagnostic Center PE Asclepius
city: Zaporizhzhia
country: Ukraine
facility: CI Zaporizhzhia Regional Dermatovenerologic Clinical Dispensary of Zaporizhzhia RC
Study officials:
References:
citation: Menter A, Cohen S, Kay J, Strand V, Gottlieb A, Hanauer S, Eduru SK, Buschke S, Lang B, Liesenfeld KH, Schaible J, McCabe D. Switching Between Adalimumab Reference Product and BI 695501 in Patients with Chronic Plaque Psoriasis (VOLTAIRE-X): A Randomized Controlled Trial. Am J Clin Dermatol. 2022 Sep;23(5):719-728. doi: 10.1007/s40257-022-00708-w. Epub 2022 Aug 7.