The Safety and Tolerability Study With ER2001 Intravenous Injection in Adults With Early Manifest Huntington's Disease

NCT06024265 | Completed Early Phase 1

• 1 other identifier: ER2001-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, dose escalation clinic trial of ER2001 intravenous injection to evaluate safety, tolerability and pharmacokinetics of ascending single and multiple doses of intravenously administered ER2001 in patients with early manifest Huntington's Disease. Furthermore, pharmacodynamics in particular target engagement, and early clinical signs of efficacy will be assessed. This study will evaluate increasing doses of ER2001 in sequential cohorts. ER2001 was escalated over 4 dose levels . The planned duration of this treatment is 14 weeks.

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of adverse events (AEs) and serious adverse events (SAEs)

  To evaluate the safety and tolerability of ER2001 injection.

  Approximately 6.5 months

Secondary Outcomes (4)

• Peak Plasma Concentration (Cmax)

  Approximately 3.5 months

• Terminal half-life (t1/2)

  Approximately 3.5 months

• Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUC0-t)

  Approximately 3.5 months

• Maximum concentration (Cmax) in cerebrospinal fluid (CSF)

  Approximately 3.5 months

Other Outcomes (4)

• Immunogenicity

  approximately- 6.5 months

• Change from baseline in the concentration of mutant huntingtin (mHTT) protein in cerebrospinal fluid (CSF)

  approximately- 6.5 months

• Change from baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) score

  approximately- 6.5 months

Study Arms (1)

ER2001 Injection

EXPERIMENTAL

The minimum initial dose is 0.04mg/kg, then escalate to 0.08mg/kg, 0.16mg/kg and 0.32mg/kg. The planned duration of the treatment is 14 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 3, 4, 5, 6, 7, 8, and 14.

Drug: ER2001 injection

Interventions

ER2001 injection DRUG

The minimum initial dose is 0.04mg/kg, then escalate to 0.08mg/kg, 0.16mg/kg and 0.32mg/kg. The planned duration of the treatment is 14 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 3, 4, 5, 6, 7, 8, and 14.

Also known as: ER2001 intravenous injection solution

ER2001 Injection

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient has documented ability to understand the written study informed consent forms (ICFs) at the time of screening and has provided signed written informed consent prior to any study procedures.
• Years to 55 Years. Gender is not limited.
• Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and a diagnostic classification level (DCL) of 4.
• HTT gene expansion testing with the presence of ≥40 CAG repeats.
• Ability to undergo and tolerate MRI scans.
• Ability to undergo and tolerate lumbar puncture.
• All HD medications given for motor, behavioral, and cognitive symptoms have been stable for 3 months prior to Screening.
• Other concomitant medications have been stable for 1 month prior to Screening.
• organ function measured prior to administration of study treatment.
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential. Male patients must use a condom during treatment and for 6 months after the last dose of ER2001 when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.

You may not qualify if:

• History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening.
• Current active psychosis, confusional state, or violent behavior.
• Bleeding tendency or history of coagulation disorder; As long as the investigator confirms that there is no evidence of bleeding tendency or coagulation dysfunction at present.
• ECG with corrected QT interval (QTc) \> 480 ms and/or indication of uncontrolled cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction,congestive heart failure, electrolyte disturbances, etc.)
• Patients with HIV, Treponema pallidum, Hepatitis B, or Hepatitis C infection.
• Need to take antiretroviral drugs, including antiretroviral drugs as preventive treatment.
• Current or recurrent disease, infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a subject's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule.
• Clinical diagnosis of chronic migraines.
• Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter.
• Preexisting structural brain lesions (such as tumor, arteriovenous malformation) as assessed by a centrally read MRI scan during the screening period.
• Any history of gene therapy, RNA or DNA investigational agents, such as antisense oligonucleotides (ASO), cell transplantation or any other experimental brain surgery.
• Treatment with investigational therapy within 4 weeks prior to screening or 5 drug elimination half-lives of investigational therapy, whichever is longer.
• Unable or unsafe to perform lumbar puncture on the patient.
• In the Investigator's judgment, that Parkinson's disease, multiple system atrophy and other dystonia diseases may be combined.
• Patients who are hypersensitive to any ingredients in the formulation of ER2001.

Sponsors & Collaborators

• ExoRNA Bioscience: lead

Study Sites (1)

First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510080, China

Location

Related Publications (1)

• Zhang L, Wu T, Shan Y, Li G, Ni X, Chen X, Hu X, Lin L, Li Y, Guan Y, Gao J, Chen D, Zhang Y, Pei Z, Chen X. Therapeutic reversal of Huntington's disease by in vivo self-assembled siRNAs. Brain. 2021 Dec 16;144(11):3421-3435. doi: 10.1093/brain/awab354.

  PMID: 34918046 BACKGROUND

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

Study Officials

• Xia Meng, Ph.D

  ExoRNA Bioscience

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: As designed, the single group will be divided into four cohorts. The first cohort of 1-6 participants will receive an initial dose, followed by a safety review of the included participants. If the safety is confirmed and decision made to proceed to the next higher dose, the next cohort of 3-6 participants will receive a higher dose. The planned increasing doses are 0.04, 0.08, 0.16, and 0.32 mg/kg, respectively in subsequent.

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: September 6, 2023
• Study Start: April 4, 2023
• Primary Completion: January 31, 2025
• Study Completion: September 4, 2025
• Last Updated: December 19, 2025

Record last verified: 2025-10

Locations

CN (1)