We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04535752




Registration number
NCT04535752
Ethics application status
Date submitted
24/08/2020
Date registered
2/09/2020
Date last updated
2/09/2020

Titles & IDs
Public title
A Single and Multiple Ascending Dose Study of ANX009 in Normal Healthy Volunteers (NHV)
Scientific title
A Phase 1, Randomized, Double-blind, Placebo-controlled Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Subcutaneous ANX009 in Normal Healthy Volunteers (NHV)
Secondary ID [1] 0 0
ANX009-NHV-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Safety and Tolerability in Healthy Volunteers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ANX009
Treatment: Drugs - ANX009
Treatment: Drugs - Placebo

Experimental: ANX009, Single Ascending Doses - Single dose of ANX009 with a 7-day follow-up before escalation to the next dose level.

Placebo Comparator: Placebo, Single Ascending Doses - Single doses of matching placebo

Experimental: ANX009, Multiple Ascending Doses - ANX009 once daily on Days 1-14

Placebo Comparator: Placebo, Multiple doses - Matching placebo once daily on Days 1-14


Treatment: Drugs: ANX009
Single ascending dose

Treatment: Drugs: ANX009
Multiple ascending dose

Treatment: Drugs: Placebo
Placebo matching ANX009

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety: Number of Participants Who Experienced Treatment-Emergent Adverse Events - Incidence and severity of treatment-emergent adverse events (AEs). AEs will be coded using MedDRA and severity of AEs will be graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE).
Timepoint [1] 0 0
[Time Frame: Up to Day 29 for SAD; up to Day 43 for MAD]
Secondary outcome [1] 0 0
Pharmacodynamics: Total Amount of Complement Protein in Blood (CH50) - Serum samples will be obtained to determine the amount of CH50. CH50 will be measured at a local laboratory. CH50 will be measured at a local laboratory.
Timepoint [1] 0 0
Up to Week 6
Secondary outcome [2] 0 0
Pharmacodynamics: Amount of C1 in Blood (C1q) - Serum samples will be obtained to determine the amount of C1q. C1q will be measured using a validated enzyme-linked immunosorbent assay (ELISA) method.
Timepoint [2] 0 0
Up to Week 6
Secondary outcome [3] 0 0
Pharmacokinetic: Maximum Observed Serum Concentration (Cmax) of ANX009 - Single-dose Cmax (Day 1 in SAD and MAD) and multiple-dose Cmax (Day 14 in MAD) will be determined. Blood samples will be obtained, and serum concentrations determined using a validated ELISA method.
Timepoint [3] 0 0
Pre-dose, immediately after dose, and 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 1 (SAD and MAD) and 36, 48, and 72 hours post-dose Day 1 (SAD)
Secondary outcome [4] 0 0
Pharmacokinetic: Time to Maximum Observed Serum Concentration (Tmax) of ANX009 - Tmax will be determined on Day 1 in SAD and MAD and on Day 14 in MAD. Blood samples will be obtained, and serum concentrations determined using a validated enzyme-linked immunosorbent assay (ELISA) method.
Timepoint [4] 0 0
Pre-dose, immediately after dose, and 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 1 (SAD and MAD) and 36, 48, and 72 hours post-dose Day 1 (SAD)
Secondary outcome [5] 0 0
Pharmacokinetic: Area Under the ANX009 Serum Concentration-Time Curve to Last Sample (AUC 0-t) and extrapolated through infinity (AUC 0-inf) - AUC 0-t will be determined on Day 1 in SAD and on Day 14 in MAD. Blood samples will be obtained, and serum concentrations determined using a validated enzyme-linked immunosorbent assay (ELISA) method.
Timepoint [5] 0 0
Pre-dose, immediately after dose, and 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 1 (SAD and MAD) and 36, 48, and 72 hours post-dose Day 1 (SAD)
Secondary outcome [6] 0 0
Pharmacokinetic: Terminal Half-Life (t1/2) of ANX009 - Half-life will be determined on Day 1 in SAD and on Day 1 and Day 14 in MAD. Blood samples will be obtained, and serum concentrations determined using a validated enzyme-linked immunosorbent assay (ELISA) method
Timepoint [6] 0 0
Pre-dose, immediately after dose, and 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 1 (SAD and MAD) and 36, 48, and 72 hours post-dose Day 1 (SAD)

Eligibility
Key inclusion criteria
1. Healthy male and non-pregnant, non-lactating female volunteers =18 to 59 years of age.

2. Females must be postmenopausal, surgically sterilized or willing and able to use
highly effective methods of contraception from screening through the final study
visit.

3. Males with a partner of childbearing potential must agree to use contraception from
Screening through the final study visit.

4. Documented history within 5 years of screening of previous vaccination against
encapsulated bacterial pathogens (MAD cohorts only).

5. Complete the full sequence of protocol-related doses, procedures and evaluations.

6. No alcohol and drugs of abuse at screening and baseline or through study completion.

7. Discontinue use of nutritional supplements and prescription and over-the-counter
medications (vitamins are allowed).

8. No new tattoos/piercings or elective surgery from screening through the End of Study
visit

9. Ability to understand and provide written informed consent.
Minimum age
18 Years
Maximum age
59 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects must not meet any of the following criteria:

1. Clinically significant, ongoing illness or medical condition that would jeopardize the
safety of the subject, limit participation, or compromise the interpretation of the
safety data derived from the subject.

2. Clinically significant findings on the screening or Baseline ECG or physical
examination.

3. Clinically significant abnormalities on screening or Baseline laboratory assessments.

4. An ANA titer = 1:160.

5. History of any autoimmune disease.

6. History of meningitis or septicemia.

7. Clinically significant infection that required medical intervention (not including
antibiotic prophylaxis) within 1 month prior to study drug dosing.

8. Known genetic deficiencies of the complement cascade system or immunodeficiency.

9. Treatment with an investigational therapeutic agent within 30 days prior to study drug
dosing.

10. Use of immunosuppressants or corticosteroids within 30 days prior to study drug
dosing.

11. Active alcohol abuse, drug abuse or substance abuse.

12. Hypersensitivity to any of the excipients in the ANX009 drug product or active
substance.

13. History of previous sensitivities or allergic or anaphylactic reactions to previous
medication injections.

14. Positive for HIV Ab, Hepatitis C Ab or Hepatitis B surface antigen (HBsAg) at
screening.

15. Body weight less than 50 kg or greater than 125 kg.

16. BMI less than 18 or greater than 30 (Asians greater than 27).

17. Current smoker defined as any occasional or daily smoking of tobacco products

Study design
Purpose of the study
Basic Science
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Site 1 - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Annexon, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Nucleus Network Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmakokinetics and
pharmacodynamics of single and repeated doses of ANX009
Trial website
https://clinicaltrials.gov/show/NCT04535752
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eric Humphriss, MBA
Address 0 0
Annexon Director, Global Clinical Operations
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Eric Humphriss, MBA
Address 0 0
Country 0 0
Phone 0 0
650-822-5511
Fax 0 0
Email 0 0
ehumphriss@annexonbio.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04535752