Huntington Disease
Conditions
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).
Detailed description
The objective of this study is to evaluate the effects of IV ANX005 administered for up to 22 weeks in participants with, or at risk for, manifest HD. 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 through Week 22, with follow up visits on Weeks 24, 28, and 36. All participants will be contacted (in clinic visit or phone call) 6 months after study completion.
Interventions
DRUGANX005
Intravenous Infusion
Sponsors
Annexon, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
ANX005 administered for up to 22 weeks
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Able to walk independently and self-sufficient in basic activities of daily living (for example, 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 electroencephalogram (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. Participants with body weight \> 150 kilograms (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 participant risk. 5. Signs and symptoms of, or a diagnosis consistent with a chronic autoimmune disorder and/or an antinuclear antibody (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, ribonucleic acid (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, 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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug up to end of study (Week 36) | 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'. |
| 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 | — |
Countries
United States
Contacts
STUDY_DIRECTORBenjamin Hoehn, MD
Annexon, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 49.7 years STANDARD_DEVIATION 12.51 |
| Blood C1q | 85.589 µg/mL STANDARD_DEVIATION 14.0165 |
| Blood NfL Level | 39.51 ng/L STANDARD_DEVIATION 11.661 |
| Complement C4a in Cerebrospinal Fluid (CSF) | 15.16 micrograms (µg)/liter (L) STANDARD_DEVIATION 6.092 |
| CSF C1q | 0.2297 µg/mL STANDARD_DEVIATION 0.06239 |
| CSF Neurofilament Light Chain (NfL) Level | 3236.1 nanograms (ng)/L STANDARD_DEVIATION 816.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 28 / 28 |
| serious Total, serious adverse events | 2 / 28 |
Outcome results
None listed