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NCT03210259

The VOLTAIRE-X Trial Looks at the Effect of Switching Between Humira® and BI 695501 in Patients With Plaque Psoriasis

Completed Phase 3 Results posted Last updated 14 July 2021
What this trial tests

Phase 3 trial testing Humira® in Psoriasis in 259 participants. Completed in 16 April 2019.

Timeline
10 July 2017
Primary endpoint
16 April 2019
16 April 2019

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment259
Start date10 July 2017
Primary completion16 April 2019
Estimated completion16 April 2019
Sites49 locations across Russia, Ukraine, Germany, Poland, Hungary, United States, Latvia

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Adults 18 to 80, any sex, with Psoriasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Plasma Concentration Time Curve Over the Dosing Interval of Week 30 to 32 (AUCτ, 30-32) for Adalimumab in Plasma Primary · Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Area Under the Plasma Concentration Time Curve Over the 2 weeks dosing Interval between Week 30 to 32 (AUCτ, 30-32) for Adalimumab in plasma was reported.

GroupValue95% CI
Switching Arm (Post-Randomization Period)2040± 1420
Continuous Humira (Post-Randomization Period)1980± 1600
Maximum Observed Concentration During the Dosing Interval Week 30-32 (Cmax, 30-32) for Adalimumab in Plasma Primary · Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Maximum observed concentration during the 2 weeks dosing interval between Week 30 to 32 (Cmax, 30-32) for Adalimumab in plasma was reported.

GroupValue95% CI
Switching Arm (Post-Randomization Period)7.13± 4.63
Continuous Humira (Post-Randomization Period)7.14± 5.37
Minimum Observed Concentration During the Dosing Interval of Week 30 to 32 (Cmin, 30-32) for Adalimumab in Plasma Secondary · Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Minimum Observed Concentration During the 2 weeks Dosing Interval between Week 30 to 32 (Cmin, 30-32) for Adalimumab in plasma was reported.

GroupValue95% CI
Switching Arm (Post-Randomization Period)5.04± 3.89
Continuous Humira (Post-Randomization Period)4.66± 4.19
Time to Maximum Observed Concentration During the Dosing Interval of Week 30 to 32 (Tmax, 30-32) for Adalimumab in Plasma Secondary · Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Time to Maximum Observed Concentration During the 2 weeks Dosing Interval between Week 30 to 32 (tmax, 30-32) for Adalimumab in plasma was reported.

GroupValue95% CI
Switching Arm (Post-Randomization Period)72.766.0 – 336
Continuous Humira (Post-Randomization Period)72.346.8 – 240
Percentage of Patients With a 75% Reduction in Psoriasis Area and Severity Index (PASI75) Response at Week 32 Secondary · At week 32

The PASI is an established measure of clinical efficacy for psoriasis medications. The PASI is a tool which provides a numeric scoring for patients' overall psoriasis disease state, with scores ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, trunk, upper extremities and lower extremities). Higher PASI scores indicate more severe psoriasis. PASI is generally summarized as a dichotomous outcome based on achieving over an X percent(%) reduction from baselin

GroupValue95% CI
Switching Arm (Post-Randomization Period)84.75
Continuous Humira (Post-Randomization Period)78.99
Percentage of Patients With a Static Physician's Global Assessment (sPGA) Score ≤ 1 (Clear or Almost Clear) at Week 32 Secondary · At week 32

The 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 is considered "static", which refers to the patient's disease state at the time of the assessments, without comparison to any of the patient's previous disease states (dynamic), whether at baseline or at a previous visit. A lower score indicates less body coverage and a higher score indicates more severe disease (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe). Results are reported for percentage of pat

GroupValue95% CI
Switching Arm (Post-Randomization Period)70.34
Continuous Humira (Post-Randomization Period)64.71
Number of Patients With Anti-drug Antibody (ADA) to Adalimumab at Week 32 Secondary · Immunogenicity samples were collected pre-dose at Week 32.

Number of patients with a confirmed positive anti-drug antibody (ADA) response to Adalimumab (BI 695501 or Humira) at Week 32. A participant was considered "ADA positive" if the blank normalized signal in the ADA screening assay was equal to or above the study specific ADA screening cut point factor of 1.06 and the signal inhibition by drug in the ADA confirmatory assay was equal to or above the study specific ADA confirmatory cut points (11.4% for signal inhibition with Humira and 12.0% for signal inhibition with BI 695501).

Negative
GroupValue95% CI
Switching Arm (Post-Randomization Period)11
Continuous Humira (Post-Randomization Period)6
Positive
GroupValue95% CI
Switching Arm (Post-Randomization Period)101
Continuous Humira (Post-Randomization Period)104
Total reportable
GroupValue95% CI
Switching Arm (Post-Randomization Period)112
Continuous Humira (Post-Randomization Period)110
Not reportable
GroupValue95% CI
Switching Arm (Post-Randomization Period)0
Continuous Humira (Post-Randomization Period)2
Number of Patients With Neutralizing Antibody (nAb) to Adalimumab at Week 32 Secondary · Immunogenicity samples were collected pre-dose at Week 32.

Number of patients with a positive neutralizing anti-drug antibody (nAb) response to Adalimumab (BI 695501 or Humira) at Week 32. A participant was considered "nAb positive" if the blank normalized signal in the nAb screening assay was equal to or below the study specific nAb screening cut point factor of 0.836.

Negative
GroupValue95% CI
Switching Arm (Post-Randomization Period)66
Continuous Humira (Post-Randomization Period)64
Positive
GroupValue95% CI
Switching Arm (Post-Randomization Period)46
Continuous Humira (Post-Randomization Period)46
Total reportable
GroupValue95% CI
Switching Arm (Post-Randomization Period)112
Continuous Humira (Post-Randomization Period)110
Not reportable
GroupValue95% CI
Switching Arm (Post-Randomization Period)0
Continuous Humira (Post-Randomization Period)2
Anti-drug Antibody (ADA) Titer of Patients With ADA at Week 32 Secondary · Immunogenicity samples were collected pre-dose at Week 32.

Anti-drug antibody (ADA) titer of patients with a confirmed positive ADA response to Adalimumab (BI 695501 or Humira) at Week 32.

GroupValue95% CI
Switching Arm (Post-Randomization Period)64.032.00 – 256.00
Continuous Humira (Post-Randomization Period)12816.00 – 256.00
Neutralizing Anti-drug Antibody (nAb) Titer of Patients With nAb at Week 32 Secondary · Immunogenicity samples were collected pre-dose at Week 32.

Neutralizing anti-drug antibody (nAb) titer of patients with a positive nAb response to Adalimumab (BI 695501 or Humira) at Week 32.

GroupValue95% CI
Switching Arm (Post-Randomization Period)2.01.00 – 4.00
Continuous Humira (Post-Randomization Period)2.01.00 – 2.00
Percentage of Patients With Drug-related Adverse Events (AEs) During the Post-Randomization Period Secondary · From first dose of trial post-randomization medication until 10 weeks after last dose of trial post-randomization medication, up to 44 weeks

Analysis of AEs focused on treatment-emergent adverse events (TEAEs) and is presented here for the post-randomization period (Week 14 to 58). For the post-randomization period analysis, TEAEs were defined as AEs that started or worsened on or after the first dose of trial post-randomization medication and prior to the last dose of trial post-randomization medication + 10 weeks.

GroupValue95% CI
Switching Arm (Post-Randomization Period)11.9
Continuous Humira (Post-Randomization Period)18.3

Adverse events — posted to ClinicalTrials.gov

Time frame: From first post-randomized trial medication until 10 weeks after last dose, up to 44 weeks (Post-Randomization Period). From first dose of Humira and prior to the first dose of post-randomization medication+10 weeks, up to 24 weeks (Run-In Period).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Humira Containing All RTS Subjects (Run-In Period)
Serious: 6/259 (2%)
Deaths: 1/259
Switching Arm (Post-Randomization Period)
Serious: 5/118 (4%)
Deaths: 0/118
Continuous Humira (Post-Randomization Period)
Serious: 4/120 (3%)
Deaths: 0/120

Serious adverse events (20 terms)

ReactionSystemHumira Containing All RTS …Switching Arm (Post-Random…Continuous Humira (Post-Ra…
LeukocytosisBlood and lymphatic system disorders
Microcytic anaemiaBlood and lymphatic system disorders
Acute myocardial infarctionCardiac disorders
Atrial fibrillationCardiac disorders
Sinus arrestCardiac disorders
Abdominal painGastrointestinal disorders
Pancreatitis acuteGastrointestinal disorders
DeathGeneral disorders
GastroenteritisInfections and infestations
InfluenzaInfections and infestations
Pneumonia chlamydialInfections and infestations
Diffuse axonal injuryInjury, poisoning and procedural complications
Joint dislocationInjury, poisoning and procedural complications
Ligament ruptureInjury, poisoning and procedural complications
Thermal burnInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Psoriatic arthropathyMusculoskeletal and connective tissue disorders
DemyelinationNervous system disorders
PsoriasisSkin and subcutaneous tissue disorders
Other adverse events (2 terms — click to expand)

ReactionSystemHumira Containing All RTS …Switching Arm (Post-Random…Continuous Humira (Post-Ra…
NasopharyngitisInfections and infestations
HeadacheNervous system disorders

Most-reported serious reactions: Leukocytosis, Microcytic anaemia, Acute myocardial infarction, Atrial fibrillation, Sinus arrest, Abdominal pain, Pancreatitis acute, Death.

Data from ClinicalTrials.gov NCT03210259 adverse events section.

Sponsor's own description

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®.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
    Sbidian E, Chaimani A, Garcia-Doval I, Doney L, et al · · 2022 · cited 84× · PMID 35603936 · DOI 10.1002/14651858.cd011535.pub5
  2. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
    Sbidian E, Chaimani A, Afach S, Doney L, et al · · 2020 · cited 78× · PMID 31917873 · DOI 10.1002/14651858.cd011535.pub3
  3. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
    Sbidian E, Chaimani A, Guelimi R, Garcia-Doval I, et al · · 2023 · cited 67× · PMID 37436070 · DOI 10.1002/14651858.cd011535.pub6
  4. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
    Sbidian E, Chaimani A, Garcia-Doval I, Doney L, et al · · 2021 · cited 54× · PMID 33871055 · DOI 10.1002/14651858.cd011535.pub4
  5. Switching Between Adalimumab Reference Product and BI 695501 in Patients with Chronic Plaque Psoriasis (VOLTAIRE-X): A Randomized Controlled Trial.
    Menter A, Cohen S, Kay J, Strand V, et al · · 2022 · cited 24× · PMID 35934770 · DOI 10.1007/s40257-022-00708-w
  6. The biosimilars journey: current status and ongoing challenges.
    Kos IA, Azevedo VF, Neto DE, Kowalski SC. · · 2018 · cited 9× · PMID 30302115 · DOI 10.7573/dic.212543
  7. Food and Drug Administration guidances on biosimilars: an update for the gastroenterologist.
    Epstein M. · · 2018 · cited 3× · PMID 30302126 · DOI 10.1177/1756284818799600
  8. Summary of Research: Switching Between Adalimumab Reference Product and BI 695501 in Patients with Chronic Plaque Psoriasis (VOLTAIRE-X): A Randomized Controlled Trial.
    Menter A. · · 2023 · PMID 37875714 · DOI 10.1007/s13555-023-00995-z

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