Approval Probability
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intra-striatal rAAV5-miHTT · 2 trials · 2 indications
Evaluation will be assessed by; \- Type and incidence of Adverse Events (AEs)
Evaluation will be assessed by; \- Changes from baseline in blood pressure (mmHg)
Evaluation will be assessed by; \- Changes from baseline in respiratory rate (BPM)
Evaluation will be assessed by; \- Changes from baseline in heart rate (BPM)
Evaluation will be assessed by; \- Changes from baseline in electrocardiograms (ECGs) for any clinically significant abnormalities or clinically significant worsening. (normal or abnormal)
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)
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)
Evaluation will be assessed by; \- Changes from baseline in Clinical Chemistry laboratory tests with clinical significance.
Evaluation will be assessed by; \- Changes from baseline in hematology laboratory tests with clinical significance.
Evaluation will be assessed by; \- Change from baseline in routine urinalysis test with clinical significance.
Evaluation will be assessed by; \- Change from baseline in CSF analysis with clinical significance.
Evaluation will be assessed by; \- Change over time in AAV5 vector shedding
Evaluation will be assessed by; \- Change over time in microglial activation (YKL-40) (pg/mL)
Evaluation will be assessed by; \- Change from baseline to Day 14 and Month 1 in the Montreal Cognitive Assessment (MoCA)
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)
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.
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | EXPERIMENTAL | Low dose AMT-130 (6 × 10\^12 gc/subject) |
| Cohort 2 | EXPERIMENTAL | High dose AMT-130 (6 × 10\^13 gc/subject) |
| Cohort 3 | EXPERIMENTAL | Low dose AMT-130 (6 × 10\^12 gc/subject) High dose AMT-130 (6 × 10\^13 gc/subject) |
| Cohorts 1, 2 | SHAM_COMPARATOR | Imitation (sham) surgery |
| Cohort 4 | EXPERIMENTAL | High dose rAAV5-miHTT (6x10\^13 gc/subject). |
| Name | Type | Description |
|---|---|---|
| intra-striatal rAAV5-miHTT | GENETIC | One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain |
| Imitation (sham) surgery | OTHER | Simulated surgical procedure with skin incisions only; no intrastriatal injections and no burr holes through the skull |
Inclusion Criteria: 1. Able and willing to provide written informed consent prior to the study and study-related procedure. 2. Male and female participants 25-65 years of age. 3. Cohorts 1 \& 2: 1. a DCL of 4 OR 2. a DCL of 3 with either a positive ("Yes") response to the UHDRS Question 80 (...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Novartis AG Sponsored ADR | NVS | 2 | PHASE3 | Votoplam |
| Neurocrine Biosciences, Inc. | NBIX | 1 | PHASE3 | Valbenazine |
| Alnylam Pharmaceuticals, Inc | ALNY | 1 | PHASE1 | ALN-HTT02 |
| uniQure N.V. | QURE | 2 | PHASE1 | intra-striatal rAAV5-miHTT |
| Sarepta Therapeutics, Inc. | SRPT | 1 | PHASE1 | SRP-1005 |
Intra-striatal rAAV5-miHTT, also known as AMT-130, is an investigational gene therapy being developed for Huntington's disease. It is administered directly into the striatum of the brain and is currently being studied in adults with early manifest Huntington's disease.
Intra-striatal rAAV5-miHTT is designed to deliver a microRNA that targets the huntingtin gene, which is the gene responsible for Huntington's disease. By reducing the expression of the mutant huntingtin protein, the therapy aims to address the underlying cause of the disease.
Intra-striatal rAAV5-miHTT is being developed by uniQure N.V., a biopharmaceutical company traded on NASDAQ under the ticker symbol QURE. The therapy is also referred to as AMT-130 in clinical trials.
Intra-striatal rAAV5-miHTT is currently in Phase 1 clinical development. It is an investigational therapy and has not been approved by regulatory authorities. The ongoing trials are designed to evaluate its safety and provide proof-of-concept in patients with early manifest Huntington's disease.
Intra-striatal rAAV5-miHTT is being studied in two Phase 1 clinical trials. The first, NCT04120493, is a safety and proof-of-concept study in the United States with 43 participants. The second, NCT05243017, is a safety and efficacy study in Poland and the United Kingdom with 14 participants. Both trials are active but not recruiting.
Yes, intra-striatal rAAV5-miHTT is also known as AMT-130. The name intra-striatal rAAV5-miHTT describes the delivery method and the active agent, while AMT-130 is the product code used by the developer, uniQure, in clinical trial documentation.