Clinical trial NCT02882009: A Study to Assess the Impact of Speed and Site of Subcutaneous Injection on Pain, Tolerability, Safety, and Pharmacokinetics of Gantenerumab in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-08-29
Enrollment: 48
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Local Pain as Assessed Using Visual Analog Scale (VAS)
timeFrame: Immediately after the injection on Day 1
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Gantenerumab
timeFrame: 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
measure: Area Under the VAS Pain-Time Curve From Time 0 to 20 Minutes (AUC[0-20])
timeFrame: 0 to 20 minutes after injection on Day 1
measure: Local Pain as Assessed Using Verbal Rating Scale (VRS) Score
timeFrame: Immediately after the injection on Day 1
measure: Number of Participants With Skin Reactivity, as Assessed Using a 0 (No Reactivity) to 3 (Severe Reactivity) Scale
timeFrame: Immediately post-dose to 6 hours on Day 1
measure: Number of Participants With Adverse Events
timeFrame: From Screening to Day 85
measure: Number of Participants With Anti-Gantenerumab Antibodies (ADAs)
timeFrame: Day 1 (predose [Hour 0]) and Day 85
measure: Maximum Observed Plasma Concentration (Cmax) of Gantenerumab
timeFrame: 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
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: PRA International Clinical Pharmacology Center (EDS US Clinic)
state: Kansas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.