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

An Open-Label, Dose Escalation Early Phase 1 Study of ER2001 Intravenous Injection in Adults With Early Manifest Huntington's Disease

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.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: ER2001 injection

Detailed Description

Participants will receive totally 8 intravenous injections of ER2001 on the first day of the study, after 2 weeks they will receive 6 injections at weekly intervals, followed by 1 injections at 6 weeks interval. The treatment period of 14 weeks will be followed by an observation phase of 84 days . A modified 3 plus 3 dose-escalation design will be employed with escalating rules set according to the incidence of dose-limiting toxicity (DLT). The first cohort of 1-6 participants will receive a low dose. After safety analysis the next cohort of 3-6 will received a higher dose. Planned doses for increase in subsequent cohorts are 0.04, 0.08, 0.16, and 0.32 mg/kg. Decision to proceed to the next higher dose cohort will be based upon a safety review of the included participants. Treatment will continue until intolerable toxicity or as per patient preference.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • First Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. 25 Years to 55 Years. Gender is not limited.
3. 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.
4. HTT gene expansion testing with the presence of ≥40 CAG repeats.
5. Ability to undergo and tolerate MRI scans.
6. Ability to undergo and tolerate lumbar puncture.
7. All HD medications given for motor, behavioral, and cognitive symptoms have been stable for 3 months prior to Screening.
8. Other concomitant medications have been stable for 1 month prior to Screening.
9. organ function measured prior to administration of study treatment.
10. 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.

Exclusion Criteria:

1. 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.
2. Current active psychosis, confusional state, or violent behavior.
3. 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.
4. 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.)
5. Patients with HIV, Treponema pallidum, Hepatitis B, or Hepatitis C infection.
6. Need to take antiretroviral drugs, including antiretroviral drugs as preventive treatment.
7. 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.
8. Clinical diagnosis of chronic migraines.
9. Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter.
10. Preexisting structural brain lesions (such as tumor, arteriovenous malformation) as assessed by a centrally read MRI scan during the screening period.
11. Any history of gene therapy, RNA or DNA investigational agents, such as antisense oligonucleotides (ASO), cell transplantation or any other experimental brain surgery.
12. Treatment with investigational therapy within 4 weeks prior to screening or 5 drug elimination half-lives of investigational therapy, whichever is longer.
13. Unable or unsafe to perform lumbar puncture on the patient.
14. In the Investigator's judgment, that Parkinson's disease, multiple system atrophy and other dystonia diseases may be combined.
15. Patients who are hypersensitive to any ingredients in the formulation of ER2001.
16. Malignancy within 5 years of screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
17. Concurrent or planned concurrent participation in any interventional clinical study, including explicit pharmacological and non-pharmacological interventions. Observational studies are acceptable.
18. Any serious medical condition or clinically significant laboratory, vital signs, or abnormalities at screening that, in the Investigator's judgment, precludes the patient's safe participation in and completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ER2001 Injection; 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; 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.; Other Names: ER2001 intravenous injection solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	To assess the Pharmacokinetics (PK) of ER2001 injection.	Approximately 3.5 months
Terminal half-life (t1/2)	To assess the Pharmacokinetics (PK) of ER2001 injection.	Approximately 3.5 months
Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUC0-t)	To assess the Pharmacokinetics (PK) of ER2001 injection.	Approximately 3.5 months
Maximum concentration (Cmax) in cerebrospinal fluid (CSF)	To assess the Pharmacokinetics (PK) of ER2001 injection.	Approximately 3.5 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	To collect the incidence of Anti-Drug Antibodies (ADAs).	approximately- 6.5 months
Change from baseline in the concentration of mutant huntingtin (mHTT) protein in cerebrospinal fluid (CSF)	To assess the dose-response relationship of ER2001 injection on mHTT protein change from baseline in cerebrospinal fluid (CSF).	approximately- 6.5 months
Change from baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) score	UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. The UHDRS TFC comprises 5 functional domains associated with disability (occupation, finances, domestic chores, activities of daily living, and care level), with scores on each item ranging from 0 to either 2 or 3. The TFC total score is the sum of the 5 TFC items and can range from 0 to 13, with greater scores indicating higher functioning. Negative change from baseline indicates worsening.	approximately- 6.5 months
Change from baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score (TMS) score	UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.	approximately- 6.5 months

Collaborators and Investigators

• Sponsor: ExoRNA Bioscience
• Investigators: Study Chair: Xia Meng, Ph.D, ExoRNA Bioscience

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2023
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: May 25, 2023
• First Submitted That Met QC Criteria: August 29, 2023
• First Posted (Actual): September 6, 2023

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Genetic Diseases, Inborn; Neurocognitive Disorders; Cognition Disorders; Dementia; Neurodegenerative Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Dyskinesias; Chorea; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Huntington Disease
• Other Study ID Numbers: ER2001-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No