Single Dose Study of ANX005 in Healthy Volunteers

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

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.

Study Overview

• Status: Terminated
• Conditions: Safety and Tolerability in Healthy Volunteers
• Intervention / Treatment: Drug: ANX005; Drug: IVIg; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ANX005 Monotherapy; ANX005 intravenous infusion	Drug: ANX005; Single ascending dose intravenous infusion
EXPERIMENTAL: ANX005 and IVIg Combination Therapy; ANX005 intravenous infusion in combination with intravenous immunoglobulin (IVIg)	Drug: ANX005; Single ascending dose intravenous infusion; Drug: IVIg; IVIg infusion in Cohorts 4b and 5b only. Randomized to ANX005 followed by IVIg or placebo followed by IVIg.
PLACEBO_COMPARATOR: Placebo; Placebo intravenous infusion	Drug: Placebos; 0.9% saline intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with treatment-related adverse events as assessed by CTCAE v4.03	Safety is assessed throughout the study. Day 43 is the last visit.	Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration		Day 43
Determine effective dose of ANX005	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	Day 43
Area under the plasma concentration versus time curve (AUC)		Day 43
Terminal half-life		Day 43

Other Outcome Measures

Outcome Measure	Time Frame
Explore relationship of AUC with PD responses in serum	Day 43
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

Collaborators and Investigators

• Sponsor: Annexon, Inc.
• Investigators: Study Director: Sandy Calman, MD, Annexon Medical Monitor

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (ACTUAL): June 1, 2018
• Study Completion (ACTUAL): June 1, 2018

Study Registration Dates

• First Submitted: December 21, 2016
• First Submitted That Met QC Criteria: January 3, 2017
• First Posted (ESTIMATE): January 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: ANX005-CP01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO