A Study to Assess the Impact of Speed and Site of Subcutaneous Injection on Pain, Tolerability, Safety, and Pharmacokinetics of Gantenerumab in Healthy Participants

A Single-Center, Randomized, Open-Label, Parallel-Group, Placebo-Controlled, Cross-Over Study To Investigate the Impact of Speed of Injection and Site of Injection on Pain, Tolerability, Safety, and Pharmacokinetics Following Subcutaneous Administration of Gantenerumab in Healthy Volunteers

The purpose of this randomized, open-label, parallel-group, placebo-controlled study is to assess pain following subcutaneous (SC) administration of gantenerumab as a high-concentration liquid formulation (HCLF) at different injection speeds. The total duration of the study for each healthy participant will be up to approximately 21 weeks.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Gantenerumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • PRA International Clinical Pharmacology Center (EDS US Clinic)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female participants (healthy status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram, hematology, blood chemistry, coagulation, serology, and urinalysis)
• Body mass index between 18.0 and 30.0 kilograms per meter squared (kg/m^2), inclusive
• Female participants of childbearing potential must commit to use two acceptable forms of contraception during the study and until at least 6 months after the follow-up visit

Exclusion Criteria:

• History of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer, or cirrhosis
• History or suspicion of drugs of abuse or alcohol addiction
• Smokers who smoke more than 10 cigarettes per day or equivalent amount of tobacco as determined by history
• Pregnant or lactating women
• Positive result on hepatitis B virus (HBV), hepatitis C virus (HCV), or Human immunodeficiency virus (HIV)-1 and -2
• Any familial history of early onset Alzheimer's disease
• Prior administration of gantenerumab
• Participation in an investigational drug medicinal product or medical device study within 90 days before dosing or within seven times the elimination half-life, whichever is longer
• Any abnormal skin conditions or potentially obscuring tattoos, pigmentation, or lesions in the area intended for SC injection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gantenerumab + Placebo; Participants will be randomized to receive gantenerumab HCLF and placebo solution via SC injection according to different sequences for the site of administration and different injection speeds.	Drug: Gantenerumab; Gantenerumab as a HCLF will be administered via SC injection according to assigned treatment sequence.; Other Names: RO4909832; Drug: Placebo; Gantenerumab Placebo solution will be administered via SC injection according to assigned treatment sequence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Local Pain as Assessed Using Visual Analog Scale (VAS)	Immediately after the injection on Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Gantenerumab	0 hour (predose) and 6, 12, and 24 hours postdose on Day 1, on Days 2, 3, 4, 5, 6, 7, 8, 12, 21, 43, 64, 85
Area Under the VAS Pain-Time Curve From Time 0 to 20 Minutes (AUC[0-20])	0 to 20 minutes after injection on Day 1
Local Pain as Assessed Using Verbal Rating Scale (VRS) Score	Immediately after the injection on Day 1
Number of Participants With Skin Reactivity, as Assessed Using a 0 (No Reactivity) to 3 (Severe Reactivity) Scale	Immediately post-dose to 6 hours on Day 1
Number of Participants With Adverse Events	From Screening to Day 85
Number of Participants With Anti-Gantenerumab Antibodies (ADAs)	Day 1 (predose [Hour 0]) and Day 85
Maximum Observed Plasma Concentration (Cmax) of Gantenerumab	0 hour (predose) and 6, 12, and 24 hours postdose on Day 1, on Days 2, 3, 4, 5, 6, 7, 8, 12, 21, 43, 64, 85

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Portron A, Jordan P, Draper K, Muenzer C, Dickerson D, van Iersel T, Hofmann C. 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. Clin Ther. 2020 Jan;42(1):108-120.e1. doi: 10.1016/j.clinthera.2019.11.015. Epub 2019 Dec 26.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2016
• Primary Completion (Actual): March 22, 2017
• Study Completion (Actual): March 22, 2017

Study Registration Dates

• First Submitted: August 24, 2016
• First Submitted That Met QC Criteria: August 24, 2016
• First Posted (Estimate): August 29, 2016

Study Record Updates

• Last Update Posted (Actual): June 11, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: WP39322

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No