Switching Between Adalimumab Reference Product and BI 695501 in Patients with Chronic Plaque Psoriasis (VOLTAIRE-X) : A Randomized Controlled Trial
© 2022. The Author(s)..
BACKGROUND: BI 695501 is an FDA-approved biosimilar to adalimumab reference product (RP). VOLTAIRE-X was a randomized clinical trial to assess outcomes with a biosimilar monoclonal antibody in line with the FDA requirements for designation as an 'interchangeable' biosimilar.
OBJECTIVE: The aim of this study was to assess whether multiple switches between adalimumab RP and BI 695501 lead to equivalent pharmacokinetics and a similar safety and immunogenicity profile compared with continuous adalimumab RP.
METHODS: We conducted a phase III, double-blind, randomized controlled trial between July 19, 2017, and April 16, 2019. There were 49 investigational sites across Europe and North America. Of 323 screened patients with moderate-to-severe chronic plaque psoriasis, 259 were treated with adalimumab RP during the run-in period. Of these, 118 and 120 were randomized to the continuous or switching arms, respectively. Interventions consisted of a run-in period with adalimumab RP 80 mg subcutaneously (SC) on Day 1, then 40 mg SC every other week (EOW) Weeks 2-12. Patients were then randomized to receive adalimumab RP 40 mg EOW Weeks 14-48 (continuous arm) or BI 695501 40 mg Weeks 14 and 16, adalimumab RP 40 mg Weeks 18 and 20, and BI 695501 40 mg EOW Weeks 22 to 48 (switching arm); all interventions were given SC. Primary endpoints were pharmacokinetics parameters, area under the plasma concentration-time curve (AUCτ,30-32) and maximum observed drug plasma concentration (Cmax,30-32), measured after the third switch during the Week 30-32 dosing interval.
RESULTS: 238 patients (mean [standard deviation] age 44.9 [13.8]; 66.0% male) were treated in the switching (n = 118) or continuous arms (n = 120). Adjusted mean Cmax,30-32 was 7.08 and 7.00 μg/mL in the switching and continuous treatment arms, respectively; adjusted mean AUCτ,30-32 was 2025.8 and 1925.9 μg h/mL. Point estimate for mean ratio for AUCτ,30-32 was 105.2% (90.2% confidence interval [CI] 96.6-114.6), and 101.1% (90.2% CI 93.3-109.7) for Cmax,30-32. Both CIs were within a predefined bioequivalence range of 80.0-125.0%. Treatment-emergent adverse events led to discontinuation in 0.8% and 1.7% of patients in the switching and continuous treatment arms, and Psoriasis Area and Severity Index (PASI) scores were highly similar in the two arms across the entire trial period.
CONCLUSIONS: Pharmacokinetic equivalence was demonstrated, with highly similar efficacy and immunogenicity, and comparable safety observed in patients with chronic plaque psoriasis who received either adalimumab RP continuously or who switched between adalimumab RP and BI 695501.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT03210259 (registered July 2017); Eudract.ema.europa.eu: 2016-002254-20.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
American journal of clinical dermatology - 23(2022), 5 vom: 07. Sept., Seite 719-728 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Menter, Alan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Adalimumab |
|---|
| Anmerkungen: |
Date Completed 13.09.2022 Date Revised 31.10.2022 published: Print-Electronic ClinicalTrials.gov: NCT03210259 Citation Status MEDLINE |
|---|
| doi: |
10.1007/s40257-022-00708-w |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM34454219X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM34454219X | ||
| 003 | DE-627 | ||
| 005 | 20231226023019.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s40257-022-00708-w |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1148.xml |
| 035 | |a (DE-627)NLM34454219X | ||
| 035 | |a (NLM)35934770 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Menter, Alan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Switching Between Adalimumab Reference Product and BI 695501 in Patients with Chronic Plaque Psoriasis (VOLTAIRE-X) |b A Randomized Controlled Trial |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.09.2022 | ||
| 500 | |a Date Revised 31.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03210259 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a BACKGROUND: BI 695501 is an FDA-approved biosimilar to adalimumab reference product (RP). VOLTAIRE-X was a randomized clinical trial to assess outcomes with a biosimilar monoclonal antibody in line with the FDA requirements for designation as an 'interchangeable' biosimilar | ||
| 520 | |a OBJECTIVE: The aim of this study was to assess whether multiple switches between adalimumab RP and BI 695501 lead to equivalent pharmacokinetics and a similar safety and immunogenicity profile compared with continuous adalimumab RP | ||
| 520 | |a METHODS: We conducted a phase III, double-blind, randomized controlled trial between July 19, 2017, and April 16, 2019. There were 49 investigational sites across Europe and North America. Of 323 screened patients with moderate-to-severe chronic plaque psoriasis, 259 were treated with adalimumab RP during the run-in period. Of these, 118 and 120 were randomized to the continuous or switching arms, respectively. Interventions consisted of a run-in period with adalimumab RP 80 mg subcutaneously (SC) on Day 1, then 40 mg SC every other week (EOW) Weeks 2-12. Patients were then randomized to receive adalimumab RP 40 mg EOW Weeks 14-48 (continuous arm) or BI 695501 40 mg Weeks 14 and 16, adalimumab RP 40 mg Weeks 18 and 20, and BI 695501 40 mg EOW Weeks 22 to 48 (switching arm); all interventions were given SC. Primary endpoints were pharmacokinetics parameters, area under the plasma concentration-time curve (AUCτ,30-32) and maximum observed drug plasma concentration (Cmax,30-32), measured after the third switch during the Week 30-32 dosing interval | ||
| 520 | |a RESULTS: 238 patients (mean [standard deviation] age 44.9 [13.8]; 66.0% male) were treated in the switching (n = 118) or continuous arms (n = 120). Adjusted mean Cmax,30-32 was 7.08 and 7.00 μg/mL in the switching and continuous treatment arms, respectively; adjusted mean AUCτ,30-32 was 2025.8 and 1925.9 μg h/mL. Point estimate for mean ratio for AUCτ,30-32 was 105.2% (90.2% confidence interval [CI] 96.6-114.6), and 101.1% (90.2% CI 93.3-109.7) for Cmax,30-32. Both CIs were within a predefined bioequivalence range of 80.0-125.0%. Treatment-emergent adverse events led to discontinuation in 0.8% and 1.7% of patients in the switching and continuous treatment arms, and Psoriasis Area and Severity Index (PASI) scores were highly similar in the two arms across the entire trial period | ||
| 520 | |a CONCLUSIONS: Pharmacokinetic equivalence was demonstrated, with highly similar efficacy and immunogenicity, and comparable safety observed in patients with chronic plaque psoriasis who received either adalimumab RP continuously or who switched between adalimumab RP and BI 695501 | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov: NCT03210259 (registered July 2017); Eudract.ema.europa.eu: 2016-002254-20 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 7 | |a BI 695501 |2 NLM | |
| 650 | 7 | |a Biosimilar Pharmaceuticals |2 NLM | |
| 650 | 7 | |a Adalimumab |2 NLM | |
| 650 | 7 | |a FYS6T7F842 |2 NLM | |
| 700 | 1 | |a Cohen, Stanley |e verfasserin |4 aut | |
| 700 | 1 | |a Kay, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Strand, Vibeke |e verfasserin |4 aut | |
| 700 | 1 | |a Gottlieb, Alice |e verfasserin |4 aut | |
| 700 | 1 | |a Hanauer, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Eduru, Sravan Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Buschke, Susanne |e verfasserin |4 aut | |
| 700 | 1 | |a Lang, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Liesenfeld, Karl-Heinz |e verfasserin |4 aut | |
| 700 | 1 | |a Schaible, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a McCabe, Dorothy |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of clinical dermatology |d 2000 |g 23(2022), 5 vom: 07. Sept., Seite 719-728 |w (DE-627)NLM11594981X |x 1179-1888 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2022 |g number:5 |g day:07 |g month:09 |g pages:719-728 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s40257-022-00708-w |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2022 |e 5 |b 07 |c 09 |h 719-728 | ||