An Open Label Study of ANX005 in Subjects With, or at Risk for, Manifest Huntington's Disease

A Phase 2a Open Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous ANX005 in Subjects With, or at Risk for, Manifest Huntington's Disease

This study is a multi-center, open-label study of intravenous (IV) ANX005 in subjects with, or at risk for, manifest Huntington's Disease (HD).

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: ANX005

Detailed Description

The objective of this study is to evaluate the effects of intravenous ANX005 administered for up to 22 weeks in subjects with, or at risk for, manifest Huntington's Disease.

Subjects will receive induction dosing of ANX005 administered by IV infusion on Days 1 and 5 or 6, followed by maintenance dosing every 2 weeks through Week 22, with follow up visits on Weeks 24, 28, and 36.

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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Annexon Investigational Site 02
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Annexon Investigational Site 03
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Annexon Investigational Site 04
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Annexon Investigational Site 07
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • Annexon Investigational Site 06
  • Washington
    • Kirkland, Washington, United States, 98034
      • Annexon Investigational Site 08

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of or at risk for Huntington's disease: Genetically confirmed disease by direct DNA testing, total CAG-Age Product (CAP) score > 400 and UHDRS independence score ≥ 80.
2. Able to walk independently and self-sufficient in basic activities of daily living (e.g. eating, dressing, bathing).
3. All HD concomitant medications stable.
4. If female, must be postmenopausal (no menses for at least 2 years without an alternative medical cause), surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or agree to use highly effective methods of contraception.
5. Males with a woman of childbearing potential partner must agree to use highly effective methods of contraception.
6. Previously vaccinated against encapsulated bacterial pathogens (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) or willing to undergo vaccination.
7. Able to tolerate EEG and lumbar puncture (LP) procedures.

Exclusion Criteria:

1. Be at risk of suicide or self-harm within the preceding 12 months.
2. Chorea and/or cognitive deficits severe enough to interfere with study assessments.
3. Subjects with body weight > 150 kg.
4. Clinically significant findings on the screening laboratory testing or physical examination that are not specific to HD and may interfere with the conduct of the study or the interpretation of the data or increase subject risk.
5. Signs and symptoms of, or a diagnosis consistent with a chronic autoimmune disorder and/or an ANA titer ≥ 1:160.
6. History of previous infusion reactions, sensitivities, allergic, or anaphylactic reactions to previous medications, environmental stimuli or other substances.
7. Use of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
8. Prior treatment with any monoclonal antibody.
9. Presence of an implanted deep brain stimulation device.
10. Any history of gene therapy, RNA or DNA targeted HD specific investigational agents such as antisense oligonucleotides, cell transplantation or any experimental brain surgery.
11. Brain and spinal pathology that may interfere with cerebrospinal fluid homeostasis and circulation, increases intracranial pressure (implanted shunt or catheter), malformations or tumor.
12. Contraindication to undergoing an LP.
13. Hypersensitivity to any of the excipients in the ANX005 drug product.
14. Clinically significant intercurrent illness, medical condition, or medical history (including neurological or mental illness, HIV, any active infection, including Hepatitis B or C) that would jeopardize the safety of the subject, limit participation, or compromise the interpretation of the data derived from the subject.
15. Any known genetic deficiencies of the complement-cascade system.
16. History of chronic oral or intravenous steroid use or immunosuppressant medication use.
17. Hemoglobin, bilirubin, or lactate dehydrogenase (LDH) values that are outside normal limits and clinically significant or suggestive of hemolytic anemia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ANX005; IV	Drug: ANX005; Intravenous Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of intravenous ANX005 administered for up to 22 weeks in subjects with, or at risk for, manifest Huntington's Disease	As measured by incidence of TEAEs, SAEs, AEs related to ANX005, SAEs related to ANX005, Grade 3 or higher AEs, Grade 3 or higher AEs related to ANX005, AEs leading to study or treatment discontinuation.	Up to Week 36
Pharmacokinetics (PK) of ANX005	As measured by ANX005 serum and cerebrospinal fluid concentrations	Up to Week 36
Pharmacodynamics (PD) effects of ANX005	As measured by C1q, C4a, and NfL levels in blood and/or cerebrospinal fluid concentrations	Up to Week 36

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory effects of ANX005 on measures of efficacy	As measured by Unified Huntington's Disease Rating Scale '99 (UHDRS)	Up to Week 36

Collaborators and Investigators

• Sponsor: Annexon, Inc.
• Investigators: Study Director: Benjamin Hoehn, MD, Annexon, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Actual): January 28, 2022
• Study Completion (Actual): January 28, 2022

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: June 10, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: ANX005-HD-01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No