Clinical trial NCT03010046: Single Dose Study of ANX005 in Healthy Volunteers
Official title: A Phase 1, Randomized, Placebo-controlled, Double Blind, Single, Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ANX005 Monotherapy and ANX005 in Combination With IVIg in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Safety and Tolerability in Healthy Volunteers
Lead sponsor: Annexon, Inc.
Sponsor class: INDUSTRY
First posted: 2017-01-04
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: Day 43
Secondary outcomes:
measure: Peak plasma concentration
timeFrame: Day 43
measure: Determine effective dose of ANX005
timeFrame: Day 43
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Day 43
measure: Terminal half-life
timeFrame: Day 43
Other outcomes:
measure: Explore relationship of AUC with PD responses in serum
timeFrame: Day 43
measure: Explore relationship of AUC with PD responses in CSF
timeFrame: Day 43
measure: Explore relationship of half-life with PD responses in serum
timeFrame: Day 43
measure: Explore relationship of half-life with PD responses in CSF
timeFrame: Day 43
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
Study officials:
affiliation: Annexon Medical Monitor
name: Sandy Calman, MD
role: STUDY_DIRECTOR
affiliation: Nucleus Network Ltd
name: Jason Lickliter, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lansita JA, Mease KM, Qiu H, Yednock T, Sankaranarayanan S, Kramer S. Nonclinical Development of ANX005: A Humanized Anti-C1q Antibody for Treatment of Autoimmune and Neurodegenerative Diseases. Int J Toxicol. 2017 Nov/Dec;36(6):449-462. doi: 10.1177/1091581817740873. Epub 2017 Dec 4.