Single Dose Study of ANX005 in Healthy Volunteers

NCT03010046 — Phase 1, Terminated, 27 participants, Annexon, Inc.

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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

Registry	NCT03010046
Status	Terminated - ANX005 well tolerated at doses studied; study discontinued and initiated in patient population
Phase	Phase 1
Study type	Interventional; randomized, parallel, masking: triple, treatment
Enrollment	27 (Actual)
Sponsor	Annexon, Inc. (Industry)
Conditions	Safety and Tolerability in Healthy Volunteers
Interventions	ANX005, IVIg, Placebos (Drug)
Dates	start 2016-12-01, primary completion 2018-06-01, completion 2018-06-01, first posted 2017-01-04, last updated 2020-08-20
Locations	1 site in Australia

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
ANX005 Monotherapy	Experimental	Drug: ANX005	ANX005 intravenous infusion
ANX005 and IVIg Combination Therapy	Experimental	Drug: ANX005; Drug: IVIg	ANX005 intravenous infusion in combination with intravenous immunoglobulin (IVIg)
Placebo	Placebo comparator	Drug: Placebos	Placebo intravenous infusion

ANX005 (Drug): Single ascending dose intravenous infusion
IVIg (Drug): IVIg infusion in Cohorts 4b and 5b only. Randomized to ANX005 followed by IVIg or placebo followed by IVIg.
Placebos (Drug): 0.9% saline intravenous infusion

+Outcome measures

Primary outcomes

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 outcomes

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 outcomes

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]

+Eligibility

Sex: All, ages: 18 Years to any, accepts healthy volunteers

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.

+Locations (1)

Facility	City	Country	Status
Nucleus Network	Melbourne, Victoria	Australia

+Publications

Results publication: 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. PMID 29202623

+Investigators

Sandy Calman, MD, Study director, Annexon Medical Monitor
Jason Lickliter, MBBS PhD, Principal investigator, Nucleus Network Ltd

My Notes

Public

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