Single Dose Study of ANX005 in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Safety and Tolerability in Healthy Volunteers

Intervention / Treatment
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* Drug: ANX005
* Drug: IVIg
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANX005 Monotherapy<br>ANX005 intravenous infusion | Drug: ANX005<br>* Single ascending dose intravenous infusion<br>|
| Experimental: ANX005 and IVIg Combination Therapy<br>ANX005 intravenous infusion in combination with intravenous immunoglobulin (IVIg) | Drug: ANX005<br>* Single ascending dose intravenous infusion<br>Drug: IVIg<br>* IVIg infusion in Cohorts 4b and 5b only. Randomized to ANX005 followed by IVIg or placebo followed by IVIg.<br>|
| Placebo Comparator: Placebo<br>Placebo intravenous infusion | Drug: Placebos<br>* 0.9% saline intravenous infusion<br>|

What is the study measuring?
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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 |