Summary

Eligibility
for people ages 25-65 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Michael Geschwind, MD, Ph.D.
Headshot of Michael Geschwind
Michael Geschwind

Description

Summary

This is the first study of AMT-130 in patients with early manifest HD and is designed to establish safety and proof-of-concept (PoC). CT-AMT-130-01 is a Phase I/II, randomized, multicenter, dose escalation, double-blind, imitation surgery, first-in-human (FIH) study.

Official Title

A Phase I/II, Randomized, Double-Blind, Sham Control Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Ascending Doses of Striatally-Administered rAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT-130) in Early Manifest Huntington's Disease

Details

AMT-130 is an investigational, single administration gene therapy intended to modify the disease course for HD. Preclinical studies have shown that AMT-130 lowers huntingtin protein and is associated with decreased progression of Huntington's Disease signs in animal models. This trial consists of a blinded 12-month (Cohort 1 & 2) and 12-month (Cohort 3A & 3B) Core Study Period to evaluate the safety and potential impact of AMT-130 on disease progression and an unblinded 4-year Long-Term Period with periodic follow-up visits to evaluate the safety of AMT-130 and disease progression in treated individuals. Cohort 2 Sham participants who do not cross over to receive AMT-130 treatment will have the opportunity to participate in the Optional Extended Follow-Up Period and will be followed for an additional 2 years. Following completion of the 12-month (Cohort 1 & 2) or 12-month (Cohort 3A & 3B) blinded post treatment follow-up period, once the crossover has been activated after review of data by the DSMB, subjects randomized to the imitation (sham) procedure who continue to meet inclusion/exclusion criteria will be allowed to crossover to receive AMT-130 treatment.

Keywords

Huntington's Disease, Gene therapy, AAV (adeno-associated virus), serotype 5 AAV (adeno-associated virus), serotype 5, Viral vector, miHTT, muHTT, Huntington's Disease (HD), Huntington Disease, intra-striatal rAAV5-miHTT

Eligibility

You can join if…

Open to people ages 25-65

  1. Able and willing to provide written informed consent prior to the study and study-related procedure
  2. Subjects 25 to 65 years of age of both sexes
  3. Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and EITHER a diagnostic classification level (DCL) of 4 OR a DCL of 3 if the subject either meets the definition of multidimensional manifest HD (UHDRS question 80) or has cognitive symptoms
  4. HTT gene expansion testing with the presence of ≥40 CAG repeats
  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.

You CAN'T join if...

  1. Evidence of suicide risk
  2. Receipt of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
  3. Participation in an investigational trial or investigational paradigm (such as exercise/physical activity, cognitive therapy, brain stimulation) within 60 days prior to Screening or anytime 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): a. Alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) b. Aspartate aminotransferase (AST) >2 × ULN c. Total bilirubin >2 × ULN d. Alkaline phosphatase (ALP) >2 × ULN e. Creatinine >1.5 × ULN f. Platelet count <100,000/mm3g.Prothrombin time (PT) >1.2 × ULN
  14. Partial thromboplastin time (PTT) >1.2 × ULN
  15. . Known documented COVID-19 requiring hospitalization, with a history of symptomatic diabetes or immune compromise, or with residual respiratory or cardiac symptom associated with COVID-19

Locations

  • University of California, San Francisco accepting new patients
    San Francisco California 94158 United States
  • University of Washington Medical Center accepting new patients
    Seattle Washington 98195 United States

Lead Scientist at UCSF

  • Michael Geschwind, MD, Ph.D.
    Dr. Geschwind received his M.D.and Ph.D. in neuroscience through the National Institutes of Health (NIH)-sponsored Medical Scientist Training Program (MSTP) at the Albert Einstein College of Medicine in New York.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
UniQure Biopharma B.V.
ID
NCT04120493
Phase
Phase 1/2 Huntington's Disease Research Study
Study Type
Interventional
Participants
Expecting 44 study participants
Last Updated