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

NCT04514367 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ANX005-HD-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (12)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. Serious AEs (SAEs) included death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was any AE with an onset on or after the day of infusion through Week 36 (end of study). AEs were graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE): Grade: 1=Mild, 2=Moderate, 3=Severe or medically significant but not immediately life-threatening. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.

  From first dose of study drug up to end of study (Week 36)

• Actual Dose of ANX005 Administered on Day 1

  Day 1

• Actual Dose of ANX005 Administered on Week 22

  Week 22

• Area Under the Concentration Versus Time Curve From Time 0 to t (AUC0-t) of ANX005 at Day 1

  Pre-dose up to 4 hours post-dose on Day 1

• CSF Free Complement Component 1q (C1q) at Day 1

  Predose at Baseline (Day 1)

• Blood Free C1q at Day 1

  Predose at Baseline (Day 1)

• Change From Baseline in Complement C4a in CSF at Week 24

  Baseline, Week 24

• Change From Baseline in Complement C4a in CSF at Week 36

  Baseline, Week 36

• Change From Baseline in CSF NfL Level at Week 24

  Baseline, Week 24

• Change From Baseline in CSF NfL Level at Week 36

  Baseline, Week 36

• Change From Baseline in Blood NfL Level at Week 24

  Baseline, Week 24

• Change From Baseline in Blood NfL Level at Week 36

  Baseline, Week 36

Study Arms (1)

ANX005

EXPERIMENTAL

Participants will receive induction dosing of ANX005 administered by IV infusion on Days 1 and 5 or 6, followed by maintenance dosing every 2 weeks (Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22) with follow up visits on Weeks 24, 28, and 36.

Drug: ANX005

Interventions

ANX005 DRUG

Intravenous Infusion

ANX005

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of or at risk for HD: Genetically confirmed disease by direct deoxyribonucleic acid (DNA) testing, total cytosine-adenine-guanine (CAG)-Age Product (CAP) score \> 400 and UHDRS independence score ≥ 80.
• Able to walk independently and self-sufficient in basic activities of daily living (for example, eating, dressing, bathing).
• All HD concomitant medications stable.
• 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.
• Males with a woman of childbearing potential partner must agree to use highly effective methods of contraception.
• Previously vaccinated against encapsulated bacterial pathogens (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) or willing to undergo vaccination.
• Able to tolerate electroencephalogram (EEG) and lumbar puncture (LP) procedures.

You may not qualify if:

• Be at risk of suicide or self-harm within the preceding 12 months.
• Chorea and/or cognitive deficits severe enough to interfere with study assessments.
• Participants with body weight \> 150 kilograms (kg).
• 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 participant risk.
• Signs and symptoms of, or a diagnosis consistent with a chronic autoimmune disorder and/or an antinuclear antibody (ANA) titer ≥ 1:160.
• History of previous infusion reactions, sensitivities, allergic, or anaphylactic reactions to previous medications, environmental stimuli or other substances.
• Use of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
• Prior treatment with any monoclonal antibody.
• Presence of an implanted deep brain stimulation device.
• Any history of gene therapy, ribonucleic acid (RNA) or DNA targeted HD specific investigational agents such as antisense oligonucleotides, cell transplantation or any experimental brain surgery.
• Brain and spinal pathology that may interfere with cerebrospinal fluid homeostasis and circulation, increases intracranial pressure (implanted shunt or catheter), malformations or tumor.
• Contraindication to undergoing an LP.
• Hypersensitivity to any of the excipients in the ANX005 drug product.
• Clinically significant intercurrent illness, medical condition, or medical history (including neurological or mental illness, human immunodeficiency virus \[HIV\], any active infection, including Hepatitis B or C) that would jeopardize the safety of the participant, limit participation, or compromise the interpretation of the data derived from the participant.
• Any known genetic deficiencies of the complement-cascade system.

Sponsors & Collaborators

• Annexon, Inc.: lead

Study Sites (6)

Annexon Investigational Site 02

Birmingham, Alabama, 35294, United States

Location

Annexon Investigational Site 03

Englewood, Colorado, 80113, United States

Location

Annexon Investigational Site 04

Washington D.C., District of Columbia, 20057, United States

Location

Annexon Investigational Site 07

Durham, North Carolina, 27710, United States

Location

Annexon Investigational Site 06

Cincinnati, Ohio, 45221, United States

Location

Annexon Investigational Site 08

Kirkland, Washington, 98034, United States

Location

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Study Coordinator
• Organization: Annexon, Inc.

clinicaltrials@annexonbio.com

1-650-822-5500

Study Officials

• Benjamin Hoehn, MD

  Annexon, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: ANX005 administered for up to 22 weeks

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: August 14, 2020
• Study Start: September 29, 2020
• Primary Completion: August 29, 2022
• Study Completion: August 29, 2022
• Last Updated: August 25, 2026
• Results First Posted: August 25, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)