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

• ClinicalTrials.gov Identifier: NCT04514367
• Recruitment Status: Completed
• First Posted: August 14, 2020
• Last Update Posted: January 31, 2023
• Sponsor: Annexon, Inc.
• Information provided by (Responsible Party): Annexon, Inc.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Huntington Disease	Drug: ANX005	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: ANX005 administered for up to 22 weeks
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 17, 2020
• Actual Primary Completion Date: January 28, 2022
• Actual Study Completion Date: January 28, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: ANX005; IV	Drug: ANX005; Intravenous Infusion

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of intravenous ANX005 administered for up to 22 weeks in subjects with, or at risk for, manifest Huntington's Disease [ Time Frame: Up to Week 36 ]
   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.
2. Pharmacokinetics (PK) of ANX005 [ Time Frame: Up to Week 36 ]
   As measured by ANX005 serum and cerebrospinal fluid concentrations
3. Pharmacodynamics (PD) effects of ANX005 [ Time Frame: Up to Week 36 ]
   As measured by C1q, C4a, and NfL levels in blood and/or cerebrospinal fluid concentrations

Other Outcome Measures:

1. Exploratory effects of ANX005 on measures of efficacy [ Time Frame: Up to Week 36 ]
   As measured by Unified Huntington's Disease Rating Scale '99 (UHDRS)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Annexon Investigational Site 02

Birmingham, Alabama, United States, 35294

United States, Colorado

Annexon Investigational Site 03

Englewood, Colorado, United States, 80113

United States, District of Columbia

Annexon Investigational Site 04

Washington, District of Columbia, United States, 20057

United States, North Carolina

Annexon Investigational Site 07

Durham, North Carolina, United States, 27710

United States, Ohio

Annexon Investigational Site 06

Cincinnati, Ohio, United States, 45221

United States, Washington

Annexon Investigational Site 08

Kirkland, Washington, United States, 98034

Sponsors and Collaborators

Annexon, Inc.

Investigators

• Study Director: Benjamin Hoehn, MD; Annexon, Inc.

More Information

• Responsible Party: Annexon, Inc.
• ClinicalTrials.gov Identifier: NCT04514367
• Other Study ID Numbers: ANX005-HD-01
• First Posted: August 14, 2020
• Last Update Posted: January 31, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Huntington Disease; 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; Cognition Disorders; Neurocognitive Disorders; Mental Disorders