Baylor Scott & White, 3900 Junius Street, suite 125, Dallas, TX, 75246, USA.
Metroplex Clinical Research Center, Dallas, TX, USA.
Am J Clin Dermatol. 2022 Sep;23(5):719-728. doi: 10.1007/s40257-022-00708-w. Epub 2022 Aug 7.
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.
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.
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 (AUC) and maximum observed drug plasma concentration (C), measured after the third switch during the Week 30-32 dosing interval.
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 C was 7.08 and 7.00 μg/mL in the switching and continuous treatment arms, respectively; adjusted mean AUC was 2025.8 and 1925.9 μg h/mL. Point estimate for mean ratio for AUC was 105.2% (90.2% confidence interval [CI] 96.6-114.6), and 101.1% (90.2% CI 93.3-109.7) for C. 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.
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.
ClinicalTrials.gov: NCT03210259 (registered July 2017); Eudract.ema.europa.eu: 2016-002254-20.
BI 695501 是一种获得美国食品药品监督管理局批准的阿达木单抗仿制药，与阿达木单抗参比制剂（RP）具有生物等效性。VOLTAIRE-X 是一项随机临床试验，旨在评估生物类似药单克隆抗体在符合美国食品药品监督管理局关于“可互换”生物类似药的指定要求下的疗效。
本研究旨在评估阿达木单抗 RP 与 BI 695501 之间多次转换是否会导致与连续使用阿达木单抗 RP 相当的药代动力学以及相似的安全性和免疫原性。
我们进行了一项 3 期、双盲、随机对照临床试验，时间为 2017 年 7 月 19 日至 2019 年 4 月 16 日。在欧洲和北美的 49 个研究点进行了筛选。在 323 名中度至重度慢性斑块型银屑病患者中，有 259 名患者在导入期接受阿达木单抗 RP 治疗。其中，118 名和 120 名患者分别被随机分配到连续治疗组或转换组。干预措施包括阿达木单抗 RP 80mg 皮下（SC）注射第 1 天，然后每隔一周（EOW）第 2-12 周 40mg SC。随后，患者随机接受阿达木单抗 RP 40mg EOW 第 14-48 周（连续治疗组）或 BI 695501 第 14 周和第 16 周、阿达木单抗 RP 第 18 周和第 20 周、BI 695501 第 40mg EOW 第 22 周到第 48 周（转换治疗组）；所有干预措施均为 SC 给药。主要终点是第 30-32 周给药间隔期间第 3 次转换后的药代动力学参数、曲线下血浆浓度-时间曲线面积（AUC）和最大观察到的药物血浆浓度（C）。
238 名患者（平均[标准差]年龄 44.9[13.8]；66.0%为男性）被分配到转换（n=118）或连续治疗组（n=120）。调整后的平均 C 分别为 7.08μg/mL 和 7.00μg/mL；调整后的平均 AUC 分别为 2025.8μg·h/mL 和 1925.9μg·h/mL。AUC 的平均比值的点估计值为 105.2%（90.2%置信区间[CI]为 96.6-114.6），C 的点估计值为 101.1%（90.2%CI 为 93.3-109.7）。这两个 CI 均在 80.0-125.0%的预设生物等效性范围内。治疗中出现的不良事件导致 0.8%和 1.7%的患者在转换治疗组和连续治疗组中停药，整个试验期间，两个治疗组的银屑病面积和严重程度指数（PASI）评分非常相似。
在接受连续阿达木单抗 RP 治疗或阿达木单抗 RP 与 BI 695501 之间转换的慢性斑块型银屑病患者中，证明了药代动力学等效性，具有高度相似的疗效和免疫原性，且安全性相当。
ClinicalTrials.gov：NCT03210259（2017 年 7 月注册）；Eudract.ema.europa.eu：2016-002254-20。
