Huntington’s disease
Conditions
Interventions
Experimental group:ER2001 Injection
Control group:Placebo injection solution
Sponsors
The First Affiliated Hospital,Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
25 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Age 25–55 years (including 25 and 55 years), any gender; 2. Diagnosis of manifest HD, defined as a Diagnostic Confidence Level (DCL) score of 4; 3. HD stage I–II, with UHDRS-TFC score between 10 and 13; 4. HTT gene CAG repeat count >=40 (if there is no compliant test report showing this standard is met, peripheral blood samples need to be collected during the screening period and sent to the central laboratory for testing); 5. Able to undergo and tolerate MRI scans (e.g., no claustrophobia, no severe chorea or other conditions preventing MRI scanning or causing intolerance to scanning, no intrauterine contraceptive device, metallic braces, or other metal implants unsuitable for MRI); 6. Able to tolerate blood draws and lumbar puncture; 7. Medical, psychiatric, and neurological status stable within 12 weeks prior to enrollment; 8. All medications for HD-related motor, behavioral, and cognitive symptoms must have been stable for 12 weeks prior to screening; 9. Adequate organ function: (1) Hematological system (not having received transfusion or hematopoietic growth factor therapy within 14 days) 1) Absolute neutrophil count (ANC) >=1.5×10^9/L; 2) Platelets (PLT) >=125×10^9/L; 3) Hemoglobin (Hb) >=100 g/L; (2) Liver function 1) Total bilirubin (TBIL) =60 mL/min (Cockcroft-Gault formula); (4) Coagulation function 1) Activated partial thromboplastin time (APTT) <=1.5×ULN; 2) International normalized ratio (INR) <=1.5×ULN; 10. Female subjects of childbearing potential must have a negative pregnancy test at screening and before dosing; all male and female subjects of reproductive potential must agree to implement effective contraception from the date of signing the informed consent until six months after the last dose of study drug using a highly effective and reliable method; 11. Willing to voluntarily participate in the clinical trial and sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1. A history of attempted suicide or suicidal ideation, and planning suicide within the 12 months prior to screening (i.e., active suicidal ideation) leading to the need to visit a hospital and/or change the level of care according to the investigator's judgment, with the C-SSRS confirming current suicidal ideation. If suicidal ideation is present, a risk assessment should be conducted by a qualified mental health professional to evaluate whether it is safe for the patient to participate in the study. Participants with a history of mild passive suicidal ideation in the past 12 months (i.e., occasionally feeling life is not worth living or is very difficult) but without attempted suicide or hospitalisation are generally acceptable, but the final decision to participate in the study should be made with caution and in consultation with a qualified mental health professional. 2.Currently using antidepressants or benzodiazepines, and the dosage has not been stabilised within the 12 weeks prior to enrollment. 3.Currently has active psychosis, disturbed consciousness, or violent behavior. 4.Use within 12 weeks prior to enrollment: antipsychotics prescribed for primary independent mental disorders (i.e., schizophrenia, schizoaffective disorder, type I bipolar disorder, severe with psychotic features), cholinesterase inhibitors, memantine, amantadine, or riluzole. 5.Currently using antipsychotics due to motor symptoms or emotional instability (i.e., short tempered or aggressive behavior), and/or having an unstable dosage of tetrabenazine, valbenazine, or deutetrabenazine for at least 12 weeks prior to enrollment or expected dosage adjustment during the study. 6.According to the researchers' judgment, within the 12 months prior to enrollment, the abuse of drugs (i.e., cannabis, opiates, stimulants, hallucinogens, designer drugs) and/or alcoholism, or psychological or physiological dependence on these substances, is defined as improper use that leads to the inability to complete primary work or fulfill social responsibilities, or use in situations that cause bodily harm or legal problems, and may warrant clinical attention. 7.History of haemorrhagic diathesis or coagulopathy; platelet count below the lower limit of the normal range, as long as the researcher confirms there is currently no evidence of haemorrhagic diathesis or coagulation dysfunction, a platelet count between125-150×10^9/Lis permissible. 8.Use of antiplatelet or anticoagulant therapy, including but not limited to aspirin (unless 450 ms, etc.; (2) Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurring within 6 months before the first administration; (3) New York Heart Association (NYHA) functional class >=II or left ventricular ejection fraction (LVEF) 1000 IU/mL or >2500 copies/mL, HCV-RNA >=103 copies/mL); presence of other active viral hepatitis or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events related to ER2001, laboratory test results with clinically significant abnormalities (dose-limiting toxicity, maximum tolerated dose, recommended dose, etc.); | — |
Secondary
| Measure | Time frame |
|---|---|
| The concentration of HTT protein at various detection time points in peripheral blood/cerebrospinal fluid;Maximum concentration of ER2001 (DNA, siRNA HTT) in peripheral blood (Cmax), corresponding time to maximum count (Tmax), area under the count time curve (AUC), and other relevant PK parameters; | — |
Countries
China
Contacts
Public ContactJinsheng Zeng
The First Affiliated Hospital,Sun Yat-sen University
Outcome results
None listed