Safety and Tolerability in Healthy Volunteers
Conditions
Brief summary
This is a single-center, randomized, double-blind, placebo-controlled, ascending, single-infusion, sequential group study. Single, ascending doses will be administered to approximately 64 subjects, with an option for 1 additional multi-dose cohort in approximately 8 subjects. The primary objective is to evaluate the safety of ANX005 administered as an intravenous infusion as a single agent and in combination with intravenous immunoglobulin (IVIg). The optional multi-dose cohort will evaluate either additional subjects at the maximum tolerated dose or ANX005 administered as 2 infusions.
Interventions
DRUGANX005
Single ascending dose intravenous infusion
DRUGIVIg
IVIg infusion in Cohorts 4b and 5b only. Randomized to ANX005 followed by IVIg or placebo followed by IVIg.
DRUGPlacebos
0.9% saline intravenous infusion
Sponsors
Annexon, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male and females 18 years and older * Females must be postmenopausal, surgically sterilized, or willing and able to use 2 methods of contraception throughout the study and for 1 month after the final study visit * Willing and able to undergo vaccination if not vaccinated recently
Exclusion criteria
* History of any autoimmune disease, meningitis, septicemia or pneumonia * History of hypercoagulable diseases, hyperviscosity, thrombosis, renal dysfunction or acute renal failure * Known genetic deficiencies of the complement cascade system * History of conditions whose symptoms and effects could alter protein catabolism or IgG utilization, e.g. protein-losing enteropathies or nephrotic syndrome * Body weight less than 50 kg or greater than 100 kg * Hypersensitivity or allergic reactions to any excipients in the ANX005 drug product * (Cohorts 4b and 5b) Known selective IgA deficiency or presence of antibodies to IgA at screening * (Cohorts 4b and 5b) Prior reaction or hypersensitivity to blood products, including IVIg or any of the excipients in IVIg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with treatment-related adverse events as assessed by CTCAE v4.03 | Day 43 | Safety is assessed throughout the study. Day 43 is the last visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak plasma concentration | Day 43 | — |
| Determine effective dose of ANX005 | Day 43 | Percent of subjects with a biologic response, defined as a reduction of serum CH50 percent change from baseline at 21 and 28 days after the first ANX005 infusion |
| Area under the plasma concentration versus time curve (AUC) | Day 43 | — |
| Terminal half-life | Day 43 | — |
Other
| Measure | Time frame |
|---|---|
| Explore relationship of AUC with PD responses in CSF | Day 43 |
| Explore relationship of half-life with PD responses in serum | Day 43 |
| Explore relationship of half-life with PD responses in CSF | Day 43 |
| Explore relationship of AUC with PD responses in serum | Day 43 |
Countries
Australia
Outcome results
None listed