Pharmacokinetics, safety, and tolerability of gantenerumab Not Applicable
Conditions
Interventions
The only arm in the YP40254 study is the treatment arm. Participants will be administered with 510 mg gantenerumab subcutaneous (SC) in the abdominal area. Participants will be confined at the study s
Sponsors
Genentech, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy Chinese male and female subjects who are 18 to 60 years of age, inclusive, at the time of signing informed consent form (ICF) 2. 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 (ECG), hematology, blood chemistry, coagulation, serology, and urinalysis. Some medical conditions are allowed that are well controlled by stable medication. 3. A body mass index (BMI) between 18.0 and 30.0 kg/m², inclusive 4. A body weight between 50 to 100 kg, inclusive 5. For women of reproductive potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as defined below: 5.1. Women must remain abstinent or use contraceptive methods that result in a failure rate of <1% per year for at least 17 weeks after dosing. 5.2. A woman is considered to be of reproductive potential if she is postmenarcheal, has not reached a postmenopausal state (=12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of reproductive potential may be adapted for alignment with local guidelines or requirements. 5.3. Examples of contraceptive methods that result in a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. 9. Able to participate and willing to give written informed consent and to comply with the study restrictions
Exclusion criteria
Exclusion criteria: 1. History of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer, or cirrhosis 2. History or suspicion of drug abuse and/or drug addiction 3. History or suspicion of alcohol abuse and/or alcohol addiction. Consumption of alcohol will not be allowed from 48 hours before dosing until the end of the residential period (Day 3) and should be limited to a maximum of 14 drinks per week for males and 7 drinks per week for females (1 drink = 12 g of pure alcohol) during the out-clinic period until follow-up. 4. Smokers who smoke more than 10 cigarettes per day or an equivalent amount of tobacco as determined by history. Healthy volunteers must be able to abstain from smoking from 48 hours before dosing until the end of the residential period (Day 3). 5. Pregnant or breastfeeding, or intending to become pregnant during the study or within 17 weeks after the last dose of study drug 6. Positive serum pregnancy test result at screening or Day -1 for women of childbearing potential 7. Known human immunodeficiency virus (HIV) infection or positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV-1 antibody 8. Any familial history of early onset of AD 9. Participants who are >49 years of age with a MoCA score lower than 26 10. Confirmed (may use an average of =3 blood pressure measurements), supine systolic blood pressure (SBP) 140 mmHg or diastolic blood pressure (DBP) 90 mmHg at screening or Day -1 11. Pulse rate (PR) >90 beats per minute or 220 milliseconds, Fridericia’s correction [QTcF] > 450 milliseconds) or cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome, family history of sudden death) 13. Use of prohibited medications or herbal remedies 14. Prior administration of gantenerumab 15. Clinically significant abnormalities (as judged by the investigator) in laboratory test results (including complete blood count, chemistry panel, and urinalysis) 16. Any major illness within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to the first administration of study drug 17. Impaired hepatic function as indicated by screening AST or ALT =3 × or total bilirubin =2 × the upper limit of normal (ULN) 18. Participation in an investigational drug medicinal product or medical device study within 30 days before dosing or within seven times the elimination half-life, whichever is longer 19. Donation of blood over 500 ml within 3 months before screening, for the duration of the study, and until 1 year after dosing 20. Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this stu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Plasma concentration of gantenerumab measured using enzyme-linked immunosorbent assay (ELISA) at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 Added 15/09/2022: Area under the concentration–time curve of gantenerumab measured using noncompartmental analysis from time 0 to infinity (AUC[0-inf]) at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 Safety: 1. Nature, incidence, severity and causal relationship of adverse events (AEs) recorded through case report form (CRF) during the AE reporting period (defined as from screening to 85 days after the dose of study drug) 2. Local pain assessed using the visual analog scale (VAS) and verbal rating scale (VRS) at the following timepoint: after first needle insertion, immediately post-dose (second injection), 5 minutes, 10 minutes, 20 minutes, 1 hour, 6 hours, 24 hours and 48 hours post-dose (and at additional regular intervals at the investigator’s discretion if an adverse reaction associated with local tolerability and pain is observed) 3. Incidence of injection site reactions (ISRs) recorded through the CRF during the AE reporting period (defined as from screening to 85 days after the dose of study drug) Immunogenicity: Anti-drug antibodies (ADAs) to gantenerumab measured using ELISA on baseline and Day 85 | — |
Secondary
| Measure | Time frame |
|---|---|
| Added 15/09/2022: 1. Area under the concentration–time curve of gantenerumab measured using noncompartmental analysis from time 0 to 672 hours [AUC(0-672)], at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 2. Area under the concentration–time curve of gantenerumab from time 0 to the time of the last quantifiable concentration [AUC(0-last)] measured using noncompartmental analysis at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 3. Apparent terminal elimination half-life (t1/2) of gantenerumab measured using noncompartmental analysis at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 4. Apparent systemic clearance (CL/F) after SC dosing of gantenerumab measured using noncompartmental analysis at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 5. Apparent volume of distribution following SC dosing of gantenerumab based on the terminal phase (Vz/F) measured using noncompartmental analysis at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 6. Time to maximum observed plasma concentration (tmax) of gantenerumab measured using noncompartmental analysis at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 7. Apparent terminal rate constant (?z) of gantenerumab measured using noncompartmental analysis at pre-dose, Day 1, 2, 3, 4, 5, 6, 7, 8, 12, 21, 29, 43, 64 and 85 | — |
Countries
China
Contacts
Public ContactClinical Trials
Outcome results
None listed