A Phase I Study to Assess the Effect of Speed of Injection on Pain, Tolerability, and Pharmacokinetics After High-volume Subcutaneous Administration of Gantenerumab in Healthy Volunteers.

PURPOSE: Gantenerumab, a fully human anti-amyloid-β IgG1 monoclonal antibody that binds to aggregated forms of amyloid-β, is being investigated as a potential disease-modifying treatment for early (prodromal to mild) Alzheimer disease (AD). Our study compared the pain associated with 5- and 15-s subcutaneous injections of gantenerumab and evaluated the tolerability and pharmacokinetic properties of subcutaneous gantenerumab.
METHODS: This randomized, open-label, single-active-dose, placebo-controlled crossover study was conducted in 50 healthy volunteers aged 40-80 years with no history of clinically significant disorders, drug or alcohol abuse, familial history of early-onset AD, or prior gantenerumab exposure. Eligible participants were randomized to a sequence of one 300-mg SC gantenerumab injection into the abdomen and 2 SC placebo injections (1 into the abdomen and 1 into the thigh) during 5 or 15 s. All injections were administered at least 90 min apart. Participants were assessed for local pain by visual analog scale (VAS) and verbal rating scale; safety profiles were assessed by recording adverse events (AEs), and plasma pharmacokinetic properties were also evaluated.
FINDINGS: Immediately after the subcutaneous gantenerumab injection, the pain VAS score was numerically higher without reaching statistical significance in the 5-s versus 15-s injection group (VAS least-squares mean difference, 7.492 mm; 95% CI, -4.439-19.423 mm). In both injection speed groups, the mean pain VAS score was comparable after subcutaneous gantenerumab and placebo injections into the abdomen. Pain was reported after needle insertion and immediately after dosing, subsiding within 5 min after the dose. The pain VAS score was numerically higher after SC placebo injection into the thigh versus abdomen (5-s injection group: mean [SD] VAS score, 26.68 [27.83] vs 19.20 [25.60] mm; 15-s injection group: mean [SD] VAS score, 14.16 [20.62] vs 9.48 [12.04] mm). No serious AEs were reported; no participants withdrew because of an AE. All AEs were of mild intensity, were transient, and had resolved without sequelae at follow-up. The most common AEs were injection site reactions; redness was the most frequently observed skin reactivity event after subcutaneous gantenerumab administration (5-s injection group: 36%; 15-s injection group: 32%). After subcutaneous administration, gantenerumab reached a peak plasma concentration at a median time of 119 h (approximately 5 days); plasma concentrations declined in a monoexponential manner. Comparable pharmacokinetic profiles were observed between the injection speed groups. IMPLICATIONS: Subcutaneous gantenerumab injections at speeds of 5 and 15 s were well tolerated in healthy volunteers and could enable at-home administration by patients with AD or their caregivers. ClinicalTrials.gov identifier: NCT02882009.

RCT Entities:   Population Interventions Outcomes