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Huntington's DiseasePhase 1/2NCT04120493

Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease

A Phase 1/2 study testing intra-striatal rAAV5-miHTT in people with Huntington's Disease, run by UniQure Biopharma B.V. at 12 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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 1/2, multicenter, first-in-human (FIH) study. Read more about this study

Who is it for?
Ages 25 to 65 years
Conditions the study is for
Huntington's Disease
What is being tested?
intra-striatal rAAV5-miHTT
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
43 participants
Where
12 sitesUnited States
Study dates
6 Sep 2019to Dec 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able and willing to provide written informed consent prior to the study and study-related procedure
  • Participants 25 to 65 years of age of both sexes
  • Cohorts 1, 2, \& 4: Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and EITHER a diagnostic confidence 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
  • Cohort 3: Early manifest HD as defined by a UHDRS TFC score of ≥ 11 and EITHER a DCL of 4 or a DCL of 3 with either a positive "Yes" response to UHDRS Question 80 (multidimensional manifest diagnosis on motor, cognitive, behavioral, functional) or DSM5 criteria for cognitive disorder (Movement Disorder Society Task Force criteria).
  • HTT gene expansion testing with the presence of ≥40 CAG repeats
  • Striatal MRI volume requirements per hemisphere:
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  • Cohorts 1, 2, \& 3: Putamen ≥2.5 cm^3 (per side); Caudate ≥2.0 cm^3 (per side)
  • Cohort 4: Putamen <2.5 cm^3 (on either side); Caudate <2.0 cm^3 (on either side)
  • 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
  • Able and willing to comply with all procedures and the study visit schedule as outlined in the protocol
  • All female participants 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.

Who cannot join

  • Evidence of suicide risk
  • Receipt of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
  • 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.
  • Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter
  • Any history of gene therapy, RNA or DNA targeted HD specific investigational agents, such as antisense oligonucleotides (ASOs), cell transplantation or any other experimental brain surgery.
  • Any contraindication to 3.0 Tesla MRI as per local guidelines
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  • Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder
  • Any contraindication to lumbar puncture as per local guidelines
  • 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
  • Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study
  • Current or recurrent disease, (including pre-existing cardiovascular or pulmonary conditions) infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a participant's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule
  • Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients
  • Any known allergy to gadoteridol (ProHance)
  • 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 h. Partial thromboplastin time (PTT) >1.2 × ULN
  • Known allergy, sensitivity, or other contraindication to medications in the immunosuppression regimen in this protocol.
  • Any participant with an active infection (e.g., coronavirus disease 2019 [COVID-19]) at Screening or at the time of treatment that requires medical intervention. Participants may rescreen, or if screened eligible and an open surgical slot is available, may receive treatment after recovery.
  • Cohort 4 ONLY: Inability to establish a safe trajectory to administer AMT-130 to the target structures, as assessed by neuroimaging.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of Michigan Department of Neurology

    Ann Arbor, Michigan, 48105

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-0111

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Ohio State University

    Columbus, Ohio, 43210

  • CenExel Rocky Mountain Clinical Research

    Englewood, Colorado, 80113

  • The University of Texas

    Houston, Texas, 77030

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Virginia Commonwealth University VCU School of Medicine, Department of Neurology

    Richmond, Virginia, 23298

  • University of California, San Francisco

    San Francisco, California, 94158

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • University of Arizona (Surgical Site Only)

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: A Phase 1/2, Randomized, Double-Blind, Sham Control and Open-Label Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Doses of Striatally-Administered rAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT-130) in Early Manifest Huntington's Disease

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 1/2, multicenter, first-in-human (FIH) study. The first three cohorts of the study have completed enrollment, including the randomized, double-blind, sham-controlled cohorts. Cohort 4 is open-label.

Cohort 4 participants will receive high dose AMT-130.

Read the detailed description

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.

Cohort 1, 2, and 3 evaluated low dose and high dose AMT-130.

Cohort 4 will further evaluate the safety of high dose AMT-130 in participants with low striatal volume. All participants in Cohort 4 will receive high dose AMT-130 and will receive pre- and post-operative dexamethasone.

Cohorts 1 and 2 participants continue follow-up visits through 6 years after receipt of AMT-130. Cohorts 3 and 4 participants continue follow-up visits through 5 years after receipt of AMT-130.

Being tested
intra-striatal rAAV5-miHTT, Imitation (sham) surgery
Keywords
Gene therapy, AAV (adeno-associated virus), serotype 5 AAV (adeno-associated virus), serotype 5, Viral vector, miHTT, muHTT, Huntington's Disease (HD)
Medical subject headings
Huntington Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • intra-striatal rAAV5-miHTTGenetic

    Also called AMT-130

    One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain

  • Imitation (sham) surgeryOther

    Simulated surgical procedure with skin incisions only; no intrastriatal injections and no burr holes through the skull

Study groups in NCT04120493
Study groupRoleWhat they receive
Cohort 1ExperimentalLow dose rAAV5-miHTT (6x10^12 gc/subject). Note: gc = genome copies
Receives: Genetic: intra-striatal rAAV5-miHTT
Cohort 2ExperimentalHigh dose rAAV5-miHTT (6x10^13 gc/subject).
Receives: Genetic: intra-striatal rAAV5-miHTT
Cohorts 1, 2Sham comparatorImitation (sham) surgery
Receives: Other: Imitation (sham) surgery
Cohort 3ExperimentalLow dose rAAV5-miHTT (6x10^12 gc/subject). High dose rAAV5-miHTT (6x10^13 gc/subject).
Receives: Genetic: intra-striatal rAAV5-miHTT
Cohort 4ExperimentalHigh dose rAAV5-miHTT (6x10^13 gc/subject).
Receives: Genetic: intra-striatal rAAV5-miHTT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number and type of Adverse Events (AE)

    Safety will be assessed by adverse events (AEs) related to clinical safety laboratory tests, vital signs, electrocardiograms (ECGs), neurological and physical examinations, rAAV5 vector shedding, immunogenicity response (Cohorts 1, 2 \& 3), suicidality risk [Columbia-Suicide Severity Rating Scale [C-SSRS)], changes in global cognitive functioning [Montreal Cognitive Assessment Scale (MoCA)] and MRI measures of edema, inflammation, volume loss and structural changes.

    Measured: 12 months (Cohorts 1 & 2) and 12 months (Cohort 3)

Secondary outcomes (1)

  1. Duration of persistence of AMT-130 in the brain

    Change over time in levels of AMT-130-derived Vector DNA Expression in the Cerebrospinal Fluid (CSF)

    Measured: Collected for duration of study through month 72 (Cohorts 1 & 2) and through month 16 (Cohorts 3 & 4)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2019
  2. Study start6 Sep 2019
  3. Primary completionJun 2029 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
43 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04120493
Sponsor's protocol ID
CT-AMT-130-01
Status last verified
Oct 2025
First submitted
30 Sep 2019
Last updated
21 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pala M, Yilmaz SG. Circular RNAs, miRNAs, and Exosomes: Their Roles and Importance in Amyloid-Beta and Tau Pathologies in Alzheimer's Disease. Neural Plast. 2025 Apr 8;2025:9581369. doi: 10.1155/np/9581369. eCollection 2025.

    PubMed 40235521

  • Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017.

    PubMed 38489195

  • Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006.

    PubMed 36463457

  • Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: April 2020. J Huntingtons Dis. 2020;9(2):185-197. doi: 10.3233/JHD-200002.

    PubMed 32250312

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing intra-striatal rAAV5-miHTT in people with Huntington's Disease, run by UniQure Biopharma B.V. at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number and type of Adverse Events (AE) (time frame: 12 months (Cohorts 1 & 2) and 12 months (Cohort 3)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04120493, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2025.

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