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A Single and Multiple Ascending Dose Study of ANX009 in Normal Healthy Volunteers (NHV)

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04535752
Recruitment Status : Not yet recruiting
First Posted : September 2, 2020
Last Update Posted : September 2, 2020
Sponsor:
Collaborator:
Nucleus Network Ltd
Information provided by (Responsible Party):
Annexon, Inc.

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmakokinetics and pharmacodynamics of single and repeated doses of ANX009

Condition or disease Intervention/treatment Phase
Safety and Tolerability in Healthy Volunteers Drug: ANX009 Drug: Placebo Phase 1

Detailed Description:

In this first in human, phase 1, randomized, double-blind, placebo-controlled study, single and multiple ascending doses of ANX009 or placebo will be administered to 48 healthy subjects.

Single Ascending Dose (SAD): Each SAD subject will participate for approximately 4 weeks (3 nights in-clinic confinement).

Multiple Ascending Dose: Each MAD subject will participate for approximately 6 weeks (17 nights in-clinic confinement).

All subjects will be contacted (in clinic visit or phone call) 6 months after study completion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official 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)
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : May 1, 2021
Estimated Study Completion Date : May 1, 2021

Arm Intervention/treatment
Experimental: ANX009, Single Ascending Doses
Single dose of ANX009 with a 7-day follow-up before escalation to the next dose level.
Drug: ANX009
Single ascending dose

Placebo Comparator: Placebo, Single Ascending Doses
Single doses of matching placebo
Drug: Placebo
Placebo matching ANX009

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

Placebo Comparator: Placebo, Multiple doses
Matching placebo once daily on Days 1-14
Drug: Placebo
Placebo matching ANX009




Primary Outcome Measures :
  1. Safety: Number of Participants Who Experienced Treatment-Emergent Adverse Events [ Time Frame: [Time Frame: Up to Day 29 for SAD; up to Day 43 for MAD] ]
    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).


Secondary Outcome Measures :
  1. Pharmacodynamics: Total Amount of Complement Protein in Blood (CH50) [ Time Frame: Up to Week 6 ]
    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.

  2. Pharmacodynamics: Amount of C1 in Blood (C1q) [ Time Frame: Up to Week 6 ]
    Serum samples will be obtained to determine the amount of C1q. C1q will be measured using a validated enzyme-linked immunosorbent assay (ELISA) method.

  3. Pharmacokinetic: Maximum Observed Serum Concentration (Cmax) of ANX009 [ Time Frame: 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) ]
    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.

  4. Pharmacokinetic: Time to Maximum Observed Serum Concentration (Tmax) of ANX009 [ Time Frame: 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) ]
    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.

  5. Pharmacokinetic: Area Under the ANX009 Serum Concentration-Time Curve to Last Sample (AUC 0-t) and extrapolated through infinity (AUC 0-inf) [ Time Frame: 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) ]
    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.

  6. Pharmacokinetic: Terminal Half-Life (t1/2) of ANX009 [ Time Frame: 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) ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04535752


Contacts
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Contact: Eric Humphriss, MBA 650-822-5511 ehumphriss@annexonbio.com

Locations
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Australia
Site 1
Melbourne, Australia
Contact: Jason Lickliter, MD         
Sponsors and Collaborators
Annexon, Inc.
Nucleus Network Ltd
Investigators
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Study Director: Eric Humphriss, MBA Annexon Director, Global Clinical Operations
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Responsible Party: Annexon, Inc.
ClinicalTrials.gov Identifier: NCT04535752    
Other Study ID Numbers: ANX009-NHV-01
First Posted: September 2, 2020    Key Record Dates
Last Update Posted: September 2, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No