Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as intra-striatal rAAV5-miHTT
AMT-130 · 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 |