A Phase I Clinical Study of ER2001 Injection for the Treatment of Early Manifest Huntington's Disease.

NCT ID: NCT07339514

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-11
• Study Completion Date: 2026-05-30

Brief Summary

This is a dose escalation and expansion clinical study to evaluate the safety, tolerability, PK profile and preliminary efficacy of ER2001 Injection vs. placebo in subjects with definitive diagnosis of early manifest HD.

The study consists of a dose escalation phase (Part A, an open-label without placebo, which will be carried out firstly) and a dose expansion phase (Part B,randomized, blinded, placebo-controlled), both of which include a screening period (4 week prior to the first administration), a treatment period (for 6 consecutive weeks, once a week [QW] for 6 weeks), and a safety follow-up period (24 weeks).

Detailed Description

Two dose levels will be included in the dose escalation phase, and subjects will be in cohorts (Cohort 1, and Cohort 2) in sequence to receive the investigational drug. Either 3 or 6 subjects will be enrolled in each cohort. Dose escalation from the current cohort to the next cohort will be determined through joint review by the sponsor and the IDMC, typically based on the number of DLT(dose-limiting toxicity)s observed in subjects. If one DLT occurs in a cohort, additional 3 subjects will be enrolled in that cohort, with a total of 6 subjects. If one DLT occurs in the low-dose cohort while the administration is ongoing in the high-dose cohort, recruitment of subjects in the high-dose cohort should be held until all enrolled subjects have completed their dosing regimen and a safety assessment of at least 7 days after completion of the treatment. In addition, the IDMC will hold a meeting to decide whether further actions are necessary, e.g., dose interruption or reduction for subjects in the high-dose cohort. If two DLTs occur in a cohort, the dose will be discontinued in that cohort and any active higher dose cohorts. No more than one subject within the same cohort should initiate the treatment on the same day.

Based on review of safety, tolerability, PK and exploratory PD results in the dose escalation phase, dose expansion will be performed in 1 or 2 cohort(s) at the recommended dose levels. For the dose expansion phase, 9 subjects (including 3 subjects in the placebo control group) will be enrolled for each dose level cohort.

Conditions

Huntington Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1.ER2001 - 0.08mg/kg

The planned duration of the treatment is 6 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 2, 3, 4, 5, and 6.

Group Type: ACTIVE_COMPARATOR

ER2001 intravenous injection

Intervention Type: DRUG

The drug dose is 0.08mg/kg, or 0.32mg/kg. The planned duration of each patient's treatment is 6 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 2, 3, 4, 5, and 6.

2.ER2001 - 0.32mg/kg

The planned duration of the treatment is 6 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 2, 3, 4, 5, and 6.

Group Type: ACTIVE_COMPARATOR

ER2001 intravenous injection

Intervention Type: DRUG

The drug dose is 0.08mg/kg, or 0.32mg/kg. The planned duration of each patient's treatment is 6 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 2, 3, 4, 5, and 6.

3.Placebo Intravenous Injection

The planned duration of the treatment is 6 weeks, and Placebo will be administrated intravenously at the first day of weeks 1, 2, 3, 4, 5, and 6.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo Injection, The planned duration of the treatment is 6 weeks, and Placebo will be administrated intravenously at the first day of weeks 1, 2, 3, 4, 5, and 6.

Interventions

ER2001 intravenous injection

The drug dose is 0.08mg/kg, or 0.32mg/kg. The planned duration of each patient's treatment is 6 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 2, 3, 4, 5, and 6.

Intervention Type: DRUG

Placebo

Placebo Injection, The planned duration of the treatment is 6 weeks, and Placebo will be administrated intravenously at the first day of weeks 1, 2, 3, 4, 5, and 6.

Intervention Type: DRUG

Eligibility Criteria

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 10 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) > 450 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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ExoRNA Bioscience

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

jinsheng zeng, Ph.D

Role: STUDY_CHAIR

First Affiliated Hospital of Sun Yat-sen University

pingyi xu, Ph.D

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Guangzhou Medical University

huifang shang, Ph.D

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Countries

China

Other Identifiers

CTR20243121

Identifier Type: REGISTRY

Identifier Source: secondary_id

ER2001-102

Identifier Type: -

Identifier Source: org_study_id