IFEZUNTIRGENE INILPARVOVEC for Huntington's disease

Inclusion criteria

• {"criterion_text":"- Able and willing to provide written informed consent prior to the study and any study-related procedure.\n- Male and female participants 25 to 65 years of age.\n- Cohorts 1 & 2: Early manifest HD as defined by a UHDRS TFC score of 9 to 13 and EITHER a. a DCL of 4 OR b. 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 (American Psychiatric Association, 2013; MDS Task Force criteria). Cohort 3: Early manifest HD as defined by a UHDRS TFC score of ≥11 and EITHER a. a DCL of 4 OR b. 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 (American Psychiatric Association, 2013; MDS Task Force criteria).\n- HTT gene expansion testing with the presence of ≥40 CAG repeats.\n- Striatal MRI volume requirements per hemisphere: a. Putamen ≥2.5 cm3 (per side) b. Caudate ≥2.0 cm3 (per side)\n- 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.\n- Able and willing to comply with all procedures and the study visit schedule as outlined in the protocol.\n- All female participants of childbearing potential (FOCPs) 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."}

Exclusion criteria

• {"criterion_text":"- Evidence of suicide risk, defined as: a. Suicide attempt within 1 year prior to Screening (Visit 1/1A). b. Suicidal ideation as defined by a positive response to question 5 on the C-SSRS Suicidal Ideation Section within 60 days prior to Screening (Visit 1/1A). c. Significant risk of suicide as judged by the Investigator.\n- Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.\n- 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 (10+ hour surgical procedure) or comply with the procedures and study visit schedule.\n- Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.\n- Any known allergy to gadoteridol (ProHance®).\n- Screening laboratory values (as measured by the central laboratory): a. Alanine aminotransferase >2 × upper limit of normal (ULN) b. Aspartate aminotransferase >2 × ULN c. Total bilirubin >2 × ULN d. Alkaline phosphatase >2 × ULN e. Creatinine >1.5 × ULN f. Platelet count <100,000/mm3 g. Prothrombin time >1.2 × ULN h. Partial thromboplastin time >1.2 × ULN\n- Additional Exclusion Criteria for Participants in Cohort 3: 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.\n- Additional Exclusion Criteria for Participants in Cohort 3: Known allergy, sensitivity, or other contraindication to medications in the immunosuppression regimen in this protocol.\n- Additional Exclusion Criteria for Participants in Cohort 3: 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.\n- Receipt of an experimental agent within 60 days or 5 half-lives prior to Screening or any time over the duration of this study.\n- Participation in an investigational study or investigational paradigm (e.g., exercise/physical activity, cognitive therapy, brain stimulation) within 60 days prior to Screening or any time over the duration of this study.\n- Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter.\n- 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.\n- Any contraindication to 3.0 Tesla MRI scans or lumbar punctures as per local guidelines.\n- Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder.\n- Any contraindication to lumbar puncture as per local guidelines.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Type and incidence of AEs","definition_or_measurement_approach":"Type and incidence will be recorded as adverse events (AEs) observed during the study (as stated: \"Type and incidence of AEs\")."}
• {"endpoint_text":"- Change from baseline in vital signs, electrocardiogram (ECG) parameters, physical examinations, and neurological examinations","definition_or_measurement_approach":"Measured as change from baseline in vital signs, ECG parameters, physical and neurological examination findings."}
• {"endpoint_text":"- Change from baseline in clinical chemistry and hematology safety laboratory tests","definition_or_measurement_approach":"Measured as change from baseline in specified clinical chemistry and hematology safety laboratory tests."}
• {"endpoint_text":"- Change from baseline in routine urinalysis and CSF analysis","definition_or_measurement_approach":"Measured as change from baseline in routine urinalysis and cerebrospinal fluid (CSF) analyses."}
• {"endpoint_text":"- Change over time in AAV5 vector shedding","definition_or_measurement_approach":"Measured as change over time in shedding of AAV5 vector (time-course assessment)."}
• {"endpoint_text":"- Change over time in antibodies against AAV5, cytokines, ELISpot, astroglial activation (glial fibrillary acidic protein [GFAP]), and microglial activation (YKL-40)","definition_or_measurement_approach":"Measured as change over time in immune biomarkers: anti-AAV5 antibodies, cytokines, ELISpot results, GFAP and YKL-40 levels."}
• {"endpoint_text":"- Prospective assessment of suicidality via the Columbia-Suicide Severity Rating Scale (C-SSRS)","definition_or_measurement_approach":"Prospective assessment using the Columbia-Suicide Severity Rating Scale (C-SSRS)."}
• {"endpoint_text":"- Change from baseline to Day 14 and Month 1 in the MoCA","definition_or_measurement_approach":"Measured as change from baseline to Day 14 and Month 1 in the Montreal Cognitive Assessment (MoCA) score."}
• {"endpoint_text":"- Change from baseline in edema, inflammation, volume loss and structural changes as measured by the following MRI pulse sequences: T1, T2, and diffusion magnetic resonance imaging (dMRI)","definition_or_measurement_approach":"Measured as change from baseline in MRI-derived metrics (T1, T2, and diffusion MRI) for edema, inflammation, volume loss and structural changes."}

Secondary endpoints

• {"endpoint_text":"- Change over time in levels of AMT-130–derived vector DNA and miRNA expression in the CSF in Cohorts 1 and 2 through approval of CT-AMT-130-02 Protocol Amendment 6.0 Version 7.0","definition_or_measurement_approach":"Measured as change over time in levels of AMT-130–derived vector DNA and miRNA expression in CSF (Cohorts 1 and 2, per amendment/version stated)."}
• {"endpoint_text":"- Change over time in levels of only AMT-130-derived vector DNA in Cohorts 1 and 2 post-approval, and throughout the trial in Cohort 3.","definition_or_measurement_approach":"Measured as change over time in AMT-130–derived vector DNA levels in CSF across specified cohorts and time periods."}

Poland

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

29-07-2024

Processing Time Days

20

Number Of Sites

2

Number Of Participants

10

Primary sponsor

Full Name

uniQure biopharma B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands

Contract research organisations

Name

PPD Global Central Labs

Responsibilities

sponsorDuties codes: 4

Name

Medpace Inc.

Responsibilities

sponsorDuties code: 5

Name

Everest Clinical Research Corporation

Responsibilities

sponsorDuties code: 11

Name

Propharma Group The Netherlands B.V.

Responsibilities

sponsorDuties codes: 12

Name

Precision For Medicine Inc.

Responsibilities

sponsorDuties codes: 4

Name

Almac Clinical Services Limited

Responsibilities

sponsorDuties code: 14

Third parties

• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Aptuit (Verona) S.r.l.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Propharma Group The Netherlands B.V.","duties_or_roles":"sponsorDuties codes: 12","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"sponsorDuties code: 15 (patient travel)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"ClearPoint Neuro, Inc","duties_or_roles":"sponsorDuties code: 15 (Clinical supplies)","organisation_type":"Industry"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"sponsorDuties code: 11","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"B.Braun Medical LLC","duties_or_roles":"sponsorDuties code: 15 (Clinical supplies)","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"sponsorDuties code: 5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Inseption Group LLC","duties_or_roles":"sponsorDuties code: 6","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Unilabs A/S","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Ixico Technologies Limited","duties_or_roles":"sponsorDuties codes: 13; 15 (MRI imaging)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Arup Laboratories Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}