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Huntington DiseasePhase 1/2NCT05243017

Safety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease

A Phase 1/2 study testing intra-striatal rAAV5-miHTT in people with Huntington Disease, run by UniQure Biopharma B.V. at 4 sites in 2 countries.

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 second study of AMT-130 in patients with early manifest HD and is designed as part of an integrated two-study phase I/II program under a single data safety monitoring board (DSMB) with staggered enrollment based upon continued demonstration of safety of AMT-130 administration. Read more about this study

Who is it for?
Ages 25 to 65 years
Conditions the study is for
Huntington Disease
What is being tested?
intra-striatal rAAV5-miHTT
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
4 sitesin 2 countries
Study dates
7 Oct 2021to 7 Oct 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.
  • Male and female participants 25-65 years of age.
  • Cohorts 1 \& 2:
  • a DCL of 4 OR
  • 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 criteria for cognitive disorder (American Psychiatric Association, 2013; MDS Task Force criteria).
  • Cohort 3:
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  • a DCL of 4 OR
  • 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 criteria for cognitive disorder (American Psychiatric Association, 2013; MDS Task Force criteria).
  • HTT gene expansion testing with the presence of ≥40 CAG repeats (confirmed by genetic testing at central laboratory).
  • Striatal MRI volume requirements per hemisphere:
  • Putamen ≥2.5 cm3 (per side)
  • Caudate ≥2.0 cm3 (per 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 (FCOP) must have 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 highly effective birth control method as outlined in Section 4.5.

Who cannot join

  • 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 Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Section within 60 days prior to Screening (Visit 1/1A)
  • Significant risk of suicide as judged by the Investigator
  • 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, etc.) within 60 days prior to Screening or anytime over the duration of this study.
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  • 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 lumbar puncture or 3.0 Tesla MRI as per local guidelines.
  • Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder.
  • Any contraindication to 3.0 Tesla MRI 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 a neurosurgical procedure (10+ hour surgical 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):
  • 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 × ULN
  • Partial thromboplastin time (PTT) >1.2 × ULN
  • Known immunocompromised status including participants who have undergone organ transplantation or who test positive at Screening for the human immunodeficiency virus (HIV); or who are at risk of pathogen reactivation if immunosuppressed, including participants who test positive at screening for hepatitis C virus antibody (anti-HCV), hepatitis C virus ribonucleic acid (HCV RNA), hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc); or who have history of active tuberculosis or a positive tuberculosis blood test during screening. For participants with an indeterminate tuberculosis blood test result or positive tuberculosis test result, repeat testing is recommended.
  • Known allergy, sensitivity, or other contraindication to immunosuppression regimens 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.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Poland2 sites

  • Instytut Psychiatrii i Neurologii

    Warsaw

  • Interventional Neuro Center

    Warsaw

Other trials in Poland

United Kingdom2 sites

  • Cardiff University

    Cardiff

  • National Hospital for Neurology & Neurosurgery

    London

Other trials in United Kingdom

About this study

Official title: A Phase Ib/II Randomized, Double-Blind 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 second study of AMT-130 in patients with early manifest HD and is designed as part of an integrated two-study phase I/II program under a single data safety monitoring board (DSMB) with staggered enrollment based upon continued demonstration of safety of AMT-130 administration.

Cohort 3 participants will receive either high or low dose (1:1 randomization). Participants enrolled in Cohort 3 will also receive an immunosuppression regimen consisting of dexamethasone, sirolimus, and rituximab.

Read the detailed description

The aim of the European study is to build upon the safety demonstrated in the first human dose (FHD) randomized, double blind, sham-controlled sequential dose escalation study (CT-AMT-130-01; clinicaltrials.gov NCT04120493) being conducted in the US and expand the number of patients exposed to the two doses to provide sufficient sample size for comparisons of safety and efficacy. CT-AMT-130-02 is a Phase Ib/II open-label (Cohorts 1 \& 2), randomized (Cohort 3 only) sequential multiple dose study that will be conducted in approximately 5 to 8 European HD centers; 2 of these centers will serve as surgical sites. Both studies will share a common set of clinical, safety, imaging, and biomarker evaluations over 5 years of follow-up. The DSMB will evaluate safety and other parameters to enable the staggered treatment of patients within each of the dosing cohorts

Cohort 3 participants will receive either high or low dose AMT-130. Following completion of the Month 36 visit, they will be unblinded to their treatment arm. Cohort 3 will further evaluate the safety and exploratory efficacy data of low or high dose AMT-130. Cohort 3 participants will also receive pre and post-operative immunosuppressant therapies composed of dexamethasone, sirolimus, and rituximab.

Being tested
intra-striatal rAAV5-miHTT
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

Study groups in NCT05243017
Study groupRoleWhat they receive
Cohort 1ExperimentalLow dose AMT-130 (6 × 10^12 gc/subject)
Receives: Genetic: intra-striatal rAAV5-miHTT
Cohort 2ExperimentalHigh dose AMT-130 (6 × 10^13 gc/subject)
Receives: Genetic: intra-striatal rAAV5-miHTT
Cohort 3ExperimentalLow dose AMT-130 (6 × 10^12 gc/subject) High dose AMT-130 (6 × 10^13 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. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by Adverse Events

    Evaluation will be assessed by;

    • Type and incidence of Adverse Events (AEs)

    Measured: 6 months

  2. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by Vital Signs - Blood Pressure

    Evaluation will be assessed by;

    • Changes from baseline in blood pressure (mmHg)

    Measured: 6 months

  3. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by Vital Signs - Respiratory Rate

    Evaluation will be assessed by;

    • Changes from baseline in respiratory rate (BPM)

    Measured: 6 months

  4. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by Vital Signs - Heart Rate

    Evaluation will be assessed by;

    • Changes from baseline in heart rate (BPM)

    Measured: 6 months

  5. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by Electrocardiograms

    Evaluation will be assessed by;

    • Changes from baseline in electrocardiograms (ECGs) for any clinically significant abnormalities or clinically significant worsening. (normal or abnormal)

    Measured: 6 months

  6. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by changes documented in the neurological examinations

    Evaluation will be assessed by;

    • Changes from baseline in neurological examinations including mental status, cranial nerves, sensory, motor, fine motor, reflexes, and gait (normal or abnormal)

    Measured: 6 months

  7. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by changes documented in the physical examinations

    Evaluation will be assessed by;

    • Changes from baseline in physical examinations assessed by physical appearance, HEENT, Neck, Chest and Lungs, Cardiovascular, Abdomen, Musculoskeletal, and Genitourinary (normal or abnormal)

    Measured: 6 months

  8. Evaluate the safety and tolerability by number of participants with clinically significant changes in laboratory tests - Clinical Chemistry

    Evaluation will be assessed by;

    • Changes from baseline in Clinical Chemistry laboratory tests with clinical significance.

    Measured: 6 months

  9. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by number of participants with clinically significant laboratory tests - hematology

    Evaluation will be assessed by;

    • Changes from baseline in hematology laboratory tests with clinical significance.

    Measured: 6 months

  10. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by number of participants with clinical significant laboratory tests - urinalysis

    Evaluation will be assessed by;

    • Change from baseline in routine urinalysis test with clinical significance.

    Measured: 6 months

  11. Evaluate the safety and tolerability o by number of participants with clinical significant changes in cerebrospinal fluid (CSF) analysis

    Evaluation will be assessed by;

    • Change from baseline in CSF analysis with clinical significance.

    Measured: 6 months

  12. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by vector shedding

    Evaluation will be assessed by;

    • Change over time in AAV5 vector shedding

    Measured: 6 months

  13. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by laboratory testing serum and CSF for biomarkers

    Evaluation will be assessed by;

    • Change over time in microglial activation (YKL-40) (pg/mL)

    Measured: 6 months

  14. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by laboratory testing serum and CSF for biomarkers

    Evaluation will be assessed by;

    • Change over time in antibodies against AAV5 (g/L)

    Measured: 6 months

  15. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by laboratory testing serum and CSF for biomarkers

    Evaluation will be assessed by;

    • Change over time in cytokines (pg/mL)

    Measured: 6 months

  16. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by laboratory testing serum and CSF for biomarkers

    Evaluation will be assessed by;

    • Change over time in ELISpot

    Measured: 6 months

  17. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by laboratory testing serum and CSF for biomarkers

    Evaluation will be assessed by;

    • Change over time in astroglial activation (GFAP) (pg/mL)

    Measured: 6 months

  18. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by cognitive assessment

    Evaluation will be assessed by;

    • Change from baseline to Day 14 and Month 1 in the Montreal Cognitive Assessment (MoCA)

    Measured: 6 months

  19. Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by number of participants with changes in MRI

    Evaluation will be assessed by;

    • Change from baseline will be measured by edema, inflammation, volume loss, and structural changes as measured by the following MRI pulse sequences, T1, T2 and diffusion MRI (dMRI)

    Measured: 6 months

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 60

Timeline

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

  1. First posted16 Feb 2022
  2. Study start7 Oct 2021
  3. Primary completionMar 2029 (estimated)
  4. Study completion7 Oct 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
Randomised
Intervention model
Sequential
Model description
The first cohort will be treated with low dose, and a total of 6 enrolled participants is anticipated. The second cohort will be treated with high dose, and a total of 9 enrolled participants is anticipated. The third cohort is randomized 1:1 high to low dose randomization.
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05243017
Sponsor's protocol ID
CT-AMT-130-02
Status last verified
Mar 2025
First submitted
1 Nov 2021
Last updated
10 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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

  • Ma YM, Zhao L. Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases. Behav Neurol. 2023 Nov 23;2023:8537296. doi: 10.1155/2023/8537296. eCollection 2023.

    PubMed 38058356

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing intra-striatal rAAV5-miHTT in people with Huntington Disease, run by UniQure Biopharma B.V. at 4 sites in 2 countries.

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 15 inclusion and 28 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 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Poland, United Kingdom. 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. 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?

Evaluate the safety and tolerability of bilateral striatal delivery of AMT-130 as a total HTT gene lowering therapy in adult subjects with early manifest HD assessed by Adverse Events (time frame: 6 months). The study lists 19 primary outcomes in all. 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 NCT05243017, which also lists 3 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 10 Mar 2025.

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