Trial Outcomes & Findings for An Open Label Study of ANX005 in Participants With, or at Risk for, Manifest Huntington's Disease (NCT NCT04514367)

NCT ID: NCT04514367

Last Updated: 2026-08-25

Results Overview

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'.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

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

Results posted on

2026-08-25

Participant Flow

Participant milestones

Participant milestones
Measure
ANX005
Participants received induction dosing of ANX005 administered by intravenous (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.
Overall Study
STARTED
28
Overall Study
Received at Least 1 Dose of Study Drug
28
Overall Study
Per Protocol Set
23
Overall Study
Pharmacokinetic (PK) Analysis Set
28
Overall Study
COMPLETED
25
Overall Study
NOT COMPLETED
3

Reasons for withdrawal

Reasons for withdrawal
Measure
ANX005
Participants received induction dosing of ANX005 administered by intravenous (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.
Overall Study
Withdrawal by Subject
1
Overall Study
Adverse Event
2

Baseline Characteristics

Per protocol set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
ANX005
n=28 Participants
Participants received 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.
Age, Continuous
49.7 years
STANDARD_DEVIATION 12.51 • n=28 Participants
Sex: Female, Male
Female
12 Participants
n=28 Participants
Sex: Female, Male
Male
16 Participants
n=28 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=28 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
27 Participants
n=28 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=28 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=28 Participants
Race (NIH/OMB)
Asian
0 Participants
n=28 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=28 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=28 Participants
Race (NIH/OMB)
White
28 Participants
n=28 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=28 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=28 Participants
Complement C4a in Cerebrospinal Fluid (CSF)
15.16 micrograms (µg)/liter (L)
STANDARD_DEVIATION 6.092 • n=23 Participants • Per protocol set
CSF Neurofilament Light Chain (NfL) Level
3236.1 nanograms (ng)/L
STANDARD_DEVIATION 816.74 • n=23 Participants • Per protocol set
Blood NfL Level
39.51 ng/L
STANDARD_DEVIATION 11.661 • n=23 Participants • Per protocol set
Blood C1q
85.589 µg/mL
STANDARD_DEVIATION 14.0165 • n=28 Participants
CSF C1q
0.2297 µg/mL
STANDARD_DEVIATION 0.06239 • n=28 Participants

PRIMARY outcome

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

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

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'.

Outcome measures

Outcome measures
Measure
ANX005
n=28 Participants
Participants received 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Any TEAEs
28 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
SAEs
2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
AEs related to ANX005
28 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
SAEs related to ANX005
2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Grade ≥3 AEs
12 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Grade ≥3 AEs related to ANX005
11 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
AEs leading to study discontinuation
2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
AEs leading to discontinuation of study medications
4 Participants

PRIMARY outcome

Timeframe: Day 1

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure
ANX005
n=28 Participants
Participants received 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.
Actual Dose of ANX005 Administered on Day 1
75.0624 milligrams (mg)/kilogram (kg)
Standard Deviation 2.6694

PRIMARY outcome

Timeframe: Week 22

Population: Safety population included all enrolled participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure
ANX005
n=23 Participants
Participants received 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.
Actual Dose of ANX005 Administered on Week 22
102.6609 mg/kg
Standard Deviation 2.7408

PRIMARY outcome

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

Population: PK analysis set included all participants who received any amount of ANX005 and had evaluable ANX005 concentration data.

Outcome measures

Outcome measures
Measure
ANX005
n=28 Participants
Participants received 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.
Area Under the Concentration Versus Time Curve From Time 0 to t (AUC0-t) of ANX005 at Day 1
4290 days*µg/milliliter (mL)
Standard Deviation 818

PRIMARY outcome

Timeframe: Predose at Baseline (Day 1)

Population: PK analysis set included all participants who received any amount of ANX005 and had evaluable ANX005 concentration data.

Outcome measures

Outcome measures
Measure
ANX005
n=28 Participants
Participants received 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.
CSF Free Complement Component 1q (C1q) at Day 1
0.2297 µg/mL
Standard Deviation 0.06239

PRIMARY outcome

Timeframe: Predose at Baseline (Day 1)

Population: PK analysis set included all participants who received any amount of ANX005 and had evaluable ANX005 concentration data.

Outcome measures

Outcome measures
Measure
ANX005
n=28 Participants
Participants received 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.
Blood Free C1q at Day 1
85.589 µg/mL
Standard Deviation 14.0165

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Per protocol set included all participants who completed all 13 infusions of ANX005 and did not have major protocol violations. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure
ANX005
n=22 Participants
Participants received 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.
Change From Baseline in Complement C4a in CSF at Week 24
38.18 µg/L
Standard Deviation 14.423

PRIMARY outcome

Timeframe: Baseline, Week 36

Population: Per protocol set included all participants who completed all 13 infusions of ANX005 and did not have major protocol violations. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure
ANX005
n=20 Participants
Participants received 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.
Change From Baseline in Complement C4a in CSF at Week 36
23.28 µg/L
Standard Deviation 9.570

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Per protocol set included all participants who completed all 13 infusions of ANX005 and did not have major protocol violations. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure
ANX005
n=22 Participants
Participants received 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.
Change From Baseline in CSF NfL Level at Week 24
318.0 ng/L
Standard Deviation 618.66

PRIMARY outcome

Timeframe: Baseline, Week 36

Population: Per protocol set included all participants who completed all 13 infusions of ANX005 and did not have major protocol violations. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure
ANX005
n=20 Participants
Participants received 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.
Change From Baseline in CSF NfL Level at Week 36
508.6 ng/L
Standard Deviation 919.43

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Per protocol set included all participants who completed all 13 infusions of ANX005 and did not have major protocol violations.

Outcome measures

Outcome measures
Measure
ANX005
n=23 Participants
Participants received 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.
Change From Baseline in Blood NfL Level at Week 24
-6.53 ng/L
Standard Deviation 10.112

PRIMARY outcome

Timeframe: Baseline, Week 36

Population: Per protocol set included all participants who completed all 13 infusions of ANX005 and did not have major protocol violations. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure
ANX005
n=22 Participants
Participants received 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.
Change From Baseline in Blood NfL Level at Week 36
-2.20 ng/L
Standard Deviation 13.146

Adverse Events

ANX005

Serious events: 2 serious events
Other events: 28 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
ANX005
n=28 participants at risk
Participants received 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.
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
3.6%
1/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders
Pneumonitis
3.6%
1/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure
ANX005
n=28 participants at risk
Participants received 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.
Skin and subcutaneous tissue disorders
Rash
53.6%
15/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders
Rash maculo-papular
35.7%
10/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders
Pruritus
28.6%
8/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders
Rash macular
10.7%
3/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders
Rash pruritic
10.7%
3/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders
Dizziness
21.4%
6/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders
Headache
17.9%
5/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders
Dizziness postural
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders
Lethargy
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders
Syncope
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders
Nausea
17.9%
5/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders
Vomiting
14.3%
4/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders
Oral pain
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations
COVID-19
14.3%
4/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations
Urinary tract infection
10.7%
3/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Investigations
Blood chloride increased
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Investigations
White blood cell count decreased
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
General disorders
Fatigue
10.7%
3/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications
Fall
10.7%
3/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications
Puncture site pain
10.7%
3/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Psychiatric disorders
Irritability
10.7%
3/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Cardiac disorders
Tachycardia
14.3%
4/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders
Neck pain
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders
Pain in extremity
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders
Cough
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders
Epistaxis
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders
Flushing
10.7%
3/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders
Hypotension
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders
Orthostatic hypotension
7.1%
2/28 • From first dose of study drug up to end of study (Week 36)
Safety population included all enrolled participants who received at least 1 dose of study drug.

Additional Information

Study Coordinator

Annexon, Inc.

Phone: 1-650-822-5500

Results disclosure agreements

  • Principal investigator is a sponsor employee Written approval from the Sponsor is required before disclosing any information relative to this clinical study, and no publications initiated by Investigators may be published until all protocol-defined results are published in a manuscript. The details and processes of producing and reviewing reports, manuscripts, and presentations based on the data from this study are described in the clinical study agreement between the Sponsor and the institution of the Investigator.
  • Publication restrictions are in place

Restriction type: OTHER