Safety and Efficacy of AMT-130 in European Adults with Early Manifest Huntington Disease

Phase 1

Conditions: Huntington Disease
MedDRA version: 20.0Level: PTClassification code 10070668Term: Huntington's diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2020-001461-36-DE

Lead Sponsor: uniQure biopharma B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 15

Inclusion Criteria

1. Able and willing to provide written informed consent prior to the study and any study related procedure.
2. Male and female subjects 25 to 65 years of age.
3. Early manifest HD as defined by a UHDRS TFC score of 9 to 13 and EITHER
- a. a DCL of 4 OR
- b. a DCL of 3 with either a positive (Yes”) response to the UHDRS Question 80 (multidimensional manifest diagnosis on motor, cognitive, behavioral, functional) or DSM5 2criteria for cognitive disorder (American Psychiatric Association, 2013; MDS Task Force criteria).
4. HTT gene expansion testing with the presence of =40 CAG repeats (confirmed by genetic testing at central laboratory).
5. Striatal MRI volume requirements per hemisphere:
• Putamen =2.5 cm3 (per side)
• Caudate =2.0 cm3 (per side)
6. All HD concomitant medications (addressing motor, behavioral and cognitive symptoms) must be stable for 3 months prior to Screening with no change in clinical symptoms requiring change in medication prior to anticipated administration procedure.
7. Able and willing to comply with all procedures and the study visit schedule as outlined in the protocol.
8. All female subjects of childbearing potential (FOCP) must have a negative serum pregnancy test at Screening (and Visit 1A, as appropriate), a negative pregnancy urine dipstick at Baseline and not be breastfeeding. All FOCPs and sexually mature males must be compliant with a highly effective birth control method as outlined in Section 4.5 of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Evidence of suicide risk, defined as:
• Suicide attempt within 1 year prior to Screening (Visit 1/1A).
• Suicidal ideation as defined by a positive response to question 5 on the C-SSRS Suicidal Ideation Section within 60 days prior to Screening (Visit 1/1A)
• Significant risk of suicide as judged by the Investigator
2. Receipt of an experimental agent within 60 days or 5 half-lives prior to Screening or anytime over the duration of this study.
3. Participation in an investigational trial or investigational paradigm (e.g. exercise/physical activity, cognitive therapy, brain stimulation) within 60 days prior to Screening or any time over the duration of this study.
4. Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter.
5. Any history of gene therapy, RNA or DNA targeted HD specific investigational agents, such as antisense oligonucleotides (ASO), cell transplantation, or any other experimental brain surgery.
6. Any contraindication to 3.0 Tesla MRI as per local guidelines.
7. Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder.
8. Any contraindication to lumbar puncture as per local guidelines.
9. 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.
10. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.
11. 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.
12. Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.
13. Screening laboratory values (as measured by the central laboratory):
• Alanine aminotransferase (ALT) >2 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) >2 × ULN
• Total bilirubin >2 × ULN
• Alkaline phosphatase (ALP) >2 × ULN
• Creatinine >1.5 × ULN
• Platelet count <100,000/mm3
• Prothrombin time (PT) >1.2 x ULN
• Partial thromboplastin time (PTT) >1.2 x ULN
14. Known, documented infection with COVID-19 based upon any testing methodology:
o Within 8 weeks of anticipated Visit 2 (Baseline) for an asymptomatic patient or a patient who recovered from only mild, non-respiratory symptoms.
o Within 12 weeks of anticipated Visit 2 (Baseline) for a symptomatic patient (e.g., cough, dyspnea) who did not require hospitalization.
o At any time for a symptomatic patient who is diabetic, immunocompromised, or hospitalized.
o For any patient not already excluded by the above:
- Within 8 weeks of anticipated Visit 2 (Baseline) for any patient with residual respiratory or cardiac symptoms, such as fatigue, shortness of breath, and chest pain.
- Any patient with neurological symptoms associated with a symptomatic COVID-19 infection that might complicate assessment of HD progression.
- Any patient with a positive COVID-19 test between Visit 2 (Baseline) and Visit 3 (Treatment).