On 30 October, the biotechnology company Roche presented the latest results from its ongoing Phase Ib/IIa Brainshuttle study at the Clinical Trials in Alzheimer’s Disease congress (CTAD) in Madrid, Spain. The Brainshuttle trial is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of trontinemab in people with Mild Cognitive Impairment or mild to moderate Alzheimer's disease (AD), who are amyloid positive. The drug is administered via intravenous infusion every four 4 weeks. The interim analysis presented at CTAD included data from 160 participants.
The first part of the study, which is complete, enrolled 60 participants across four cohorts. These participants received either escalating doses of trontinemab or placebo. The second part of the study is ongoing and involved 100 participants who are being treated with either 1.8 mg/kg or 3.6 mg/kg of trontinemab or placebo. Results from the completed Part 1 study demonstrated rapid and robust amyloid plaque depletion, after 12 to 28 weeks, in participants receiving 1.8 mg/kg and 3.6 mg/kg of trontinemab.
After 28 weeks of treatment, most participants in the highest two dose groups were amyloid negative. In addition to amyloid plaque reduction, preliminary Part 1 data indicated that amyloid removal is accompanied by large magnitude changes in relevant AD biomarkers such as total tau, ptau181 and Neurogranin in cerebrospinal fluid (CSF). Trontinemab had an overall favourable safety profile. According to Roche, a “very limited” number of amyloid-related imaging abnormalities-edema/effusion (ARIA-E) cases was observed. However, Roche disclosed one participant (78 years-old) receiving treatment who experienced a brain bleed in her right front lobe and died on day 44 of the study. The company said this participant had a superficial siderosis, as well as additional lesions, signifying a probable cerebral amyloid angiopathy. As a result, Roche implemented protocol amendments, excluding participants with superficial siderosis from the study going forward.
