Pfizer Worldwide Research & Development Cambridge Massachusetts.
Massachusetts General Hospital Harvard Medical School Boston Massachusetts.
Ann Clin Transl Neurol. 2019 Mar 18;6(4):795-806. doi: 10.1002/acn3.761. eCollection 2019 Apr.
Cerebral amyloid angiopathy (CAA) is caused by cerebrovascular deposition of -amyloid fragments leading to cerebrovascular dysfunction and other brain injuries. This phase 2, randomized, double-blind trial in patients with probable CAA assessed the efficacy and safety of ponezumab, a novel monoclonal antibody against A .
Thirty-six participants aged 55-80 years with probable CAA received intravenous placebo ( = 12) or ponezumab ( = 24). The change from baseline to Days 2 and 90 in cerebrovascular reactivity (CVR) was measured in the visual cortex as the natural log of the rising slope of the BOLD fMRI response to a visual stimulus. Safety and tolerability were also assessed.
The mean change from baseline to Day 90 was 0.817 (ponezumab) and 0.958 (placebo): a mean ratio of 0.852 (90% CI 0.735-0.989) representing a trend towards CVR in the ponezumab group. This trend was not present at Day 2. There was one asymptomatic occurrence of amyloid-related imaging abnormality-edema in the ponezumab group. The total number of new cerebral microbleeds from baseline to day 90 did not differ between groups. The ponezumab group had a participant with nonfatal new cerebral hemorrhage with aphasia and a participant with subdural hemorrhage that site investigators deemed to be nondrug related. In the placebo group one participant had a fatal intracerebral hemorrhage and one participant had migraine with aura.
Ponezumab was safe and well-tolerated. The ponezumab group showed a trend towards treatment effect at Day 90 that was opposite to the hypothesized direction. The prespecified efficacy criteria were thus not met.
脑淀粉样血管病（CAA）是由β淀粉样片段在脑血管中的沉积引起的，导致脑血管功能障碍和其他脑损伤。这项针对可能患有 CAA 的患者的 2 期、随机、双盲试验评估了针对 A 的新型单克隆抗体 ponezumab 的疗效和安全性。
36 名年龄在 55-80 岁之间的可能患有 CAA 的患者接受了静脉注射安慰剂（n=12）或 ponezumab（n=24）。在视觉皮层中，通过测量 BOLD fMRI 对视觉刺激的上升斜率的自然对数来测量从基线到第 2 天和第 90 天的脑血管反应性（CVR）的变化。还评估了安全性和耐受性。
从基线到第 90 天的平均变化为 0.817（pontezumab）和 0.958（安慰剂）：平均比值为 0.852（90%CI 0.735-0.989），表明 ponezumab 组的 CVR 呈趋势。这种趋势在第 2 天并不存在。在 ponezumab 组中有一例无症状的淀粉样相关成像异常-水肿。从基线到第 90 天，新的脑微出血总数在两组之间没有差异。pontezumab 组有一名参与者发生非致命性新脑出血伴失语症，一名参与者发生硬膜下血肿，研究者认为与药物无关。在安慰剂组中，有一名参与者发生致命性颅内出血，一名参与者发生偏头痛伴先兆。
pontezumab 是安全且耐受良好的。pontezumab 组在第 90 天显示出治疗效果的趋势与假设方向相反。因此，未达到预设的疗效标准。
