To investigate the safety and tolerability of DNL919To characterize the serum PK of DNL919
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incidence, severity, and seriousness of treatment-emergent adverse event
(TEAEs)
Secondary outcome
• DNL919 serum PK parameters following single IV doses of DNL919, including but
not limited to:
o maximum concentration (Cmax)
o area under the concentration-time curve from time zero to infinity (AUCinf)
Background summary
This Phase 1 study will evaluate the safety, tolerability, PK, and PD of DNL919
for the first time in healthy participants to assess the appropriateness of
further development of DNL919 for the treatment of AD, a disease in which TREM2
activation-mediated microglial cell modulation may provide therapeutic benefit.
The principal aim of this study is to obtain safety and tolerability data when
DNL919 is administered through IV as a first dose to healthy participants. This
information, together with the PK and PD data, will inform the design of future
studies.
Study objective
To investigate the safety and tolerability of DNL919
To characterize the serum PK of DNL919
Study design
This is a Phase 1, randomized, double-blind, placebo-controlled single
ascending dose study to evaluate the safety, tolerability, PK, and PD of DNL919
administered via IV infusion.
Intervention
DNL919 or placebo
Study burden and risks
Infusion of the study drug (TREM2 antibody) might result in infusion-related
reactions. In addition, DNL919 is an investigational drug and has not been
given to human subjects before, therefore, unexpected side effects might occur
such as hypersensitivity reactions. In animals, reductions in reticulocyte and
red blood cell count (anemia) have been reported, as well as immune cell
infiltration into nerves upon repeated dosing, and myocardial degeneration and
brain necrosis upon Q1W dosing at high dose levels.
Subjects in cohort A3 and beyond might have discomfort during or after the
lumbar punctures. Moreover, subjects in cohort A6-A8 are exposed to radiation
due to the FDG-PET. Lastly, subjects in cohort A6-A8 will get an MRI scan,
which uses strong magnets that could affect metal objects inside the body.
Oyster Point Blvd 161
South San Francisco CA 94080
US
Oyster Point Blvd 161
South San Francisco CA 94080
US
Listed location countries
Age
Inclusion criteria
Healthy male participants and healthy female participants of non childbearing
potential aged between 18 and 55 years, inclusive, with a body mass index (BMI)
between 18.5 and 32 kg/m2, inclusive
Exclusion criteria
Women of childbearing potential will be excluded in this study because
reproductive toxicity studies have not yet been performed. Also, participants
with any history of clinically significant neurological, psychiatric, endocrine
(including diabetes mellitus), pulmonary, cardiovascular, gastrointestinal,
hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic
disease, or other major disorders.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-000756-10-NL |
| CCMO | NL80808.056.22 |