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    Summary
    EudraCT Number:2020-001461-36
    Sponsor's Protocol Code Number:CT-AMT-130-02
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-04-30
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2020-001461-36
    A.3Full title of the trial
    A Phase Ib/II Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Ascending Doses of Striatally-Administered rAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT 130) in Early Manifest Huntington Disease
    Eine Studie der Phase Ib/II zur Untersuchung von Sicherheits-, Verträglichkeits- und Wirksamkeitssignalen mehrerer ansteigender Dosen der über das Stratium verabreichten rAAV5-miHTT Huntingtin-Gen-(HTT-)senkenden Therapie (AMT-130) bei frühmanifester Huntington-Krankheit.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety and Efficacy of AMT-130 in European Adults with Early Manifest Huntington Disease
    Studie zur Sicherheit und Wirksamkeit von AMT-130 bei Erwachsenen mit frühmanifester Huntington-Krankheit
    A.3.2Name or abbreviated title of the trial where available
    Safety and Efficacy of AMT-130 in European Adults with Early Manifest Huntington Disease
    A.4.1Sponsor's protocol code numberCT-AMT-130-02
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsoruniQure biopharma B.V.
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportuniQure biopharma B.V.
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationuniQure biopharma B.V.
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressPaasheuvelweg 25A
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1105 BP
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+310202406000
    B.5.6E-mailn.schillemans@uniqure.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1957
    D.3 Description of the IMP
    D.3.1Product namerAAV5-miHTT
    D.3.2Product code AMT-130
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Huntington Disease
    E.1.1.1Medical condition in easily understood language
    Huntington Disease
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10070668
    E.1.2Term Huntington's disease
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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
    E.2.2Secondary objectives of the trial
    Determine the duration of persistence of AMT-130 in the brain
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Able and willing to provide written informed consent prior to the study and any study related procedure.
    2. Male and female subjects 25 to 65 years of age.
    3. 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 the UHDRS Question 80 (multidimensional manifest diagnosis on motor, cognitive, behavioral, functional) or DSM5 2criteria for cognitive disorder (American Psychiatric Association, 2013; MDS Task Force criteria).
    4. HTT gene expansion testing with the presence of ≥40 CAG repeats (confirmed by genetic testing at central laboratory).
    5. Striatal MRI volume requirements per hemisphere:
    • Putamen ≥2.5 cm3 (per side)
    • Caudate ≥2.0 cm3 (per side)
    6. 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.
    7. Able and willing to comply with all procedures and the study visit schedule as outlined in the protocol.
    8. All female subjects 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 as outlined in Section 4.5 of the protocol.
    E.4Principal exclusion criteria
    1. 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 the C-SSRS Suicidal Ideation Section within 60 days prior to Screening (Visit 1/1A)
    • Significant risk of suicide as judged by the Investigator
    2. Receipt of an experimental agent within 60 days or 5 half-lives prior to Screening or anytime over the duration of this study.
    3. Participation in an investigational trial 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.
    4. Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter.
    5. Any history of gene therapy, RNA or DNA targeted HD specific investigational agents, such as antisense oligonucleotides (ASO), cell transplantation, or any other experimental brain surgery.
    6. Any contraindication to 3.0 Tesla MRI as per local guidelines.
    7. Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder.
    8. Any contraindication to lumbar puncture as per local guidelines.
    9. 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.
    10. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.
    11. Current or recurrent disease, infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a subject’s safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule.
    12. Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.
    13. 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 x ULN
    • Partial thromboplastin time (PTT) >1.2 x ULN
    14. Known, documented infection with COVID-19 based upon any testing methodology:
    o Within 8 weeks of anticipated Visit 2 (Baseline) for an asymptomatic patient or a patient who recovered from only mild, non-respiratory symptoms.
    o Within 12 weeks of anticipated Visit 2 (Baseline) for a symptomatic patient (e.g., cough, dyspnea) who did not require hospitalization.
    o At any time for a symptomatic patient who is diabetic, immunocompromised, or hospitalized.
    o For any patient not already excluded by the above:
    − Within 8 weeks of anticipated Visit 2 (Baseline) for any patient with residual respiratory or cardiac symptoms, such as fatigue, shortness of breath, and chest pain.
    − Any patient with neurological symptoms associated with a symptomatic COVID-19 infection that might complicate assessment of HD progression.
    − Any patient with a positive COVID-19 test between Visit 2 (Baseline) and Visit 3 (Treatment).
    E.5 End points
    E.5.1Primary end point(s)
    • Type and incidence of AEs.
    • Change from baseline in vital signs, electrocardiogram (ECG) parameters, physical examinations, and neurological examinations.
    • Change from baseline in clinical chemistry and hematology safety laboratory tests.
    • Change from baseline in routine urinalysis and CSF analysis.
    • Change over time in AAV5 vector shedding.
    • Change over time in antibodies against AAV5, cytokines, enzyme-linked immunospot assay (ELISpot), astroglial activation (GFAP) and mircroglial activation (YKL-40)
    • Prospective assessment of suicidality via the Columbia-Suicide Severity Rating Scale (C-SSRS).
    • Change from baseline to Day 14 and Month 1 in the Montreal Cognitive Assessment (MoCA)
    • Change from baseline in edema, inflammation, volume loss, and structural changes as measured by the following MRI pulse sequences: T1, T2, and diffusion MRI (dMRI).
    E.5.1.1Timepoint(s) of evaluation of this end point
    • AEs - measured throughout study
    • Vital signs, chemistry panel, urinalysis, CSF analysis, neurological and physical exams - screening, baseline, Day 7, Day 14, Month 1, 3, 6, 9, 12, 15 18, 24, 30, 36, 48, 60.
    [Some assessment time points vary - See Schedule of Assessments in protocol for full details]
    • Vector shedding - baseline, Day 14, Month 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60.
    • AAV5, cytokines, and ELISpot - baseline, Day7, Day 14, Month 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60.
    • C-SSRS - screening, baseline, Day 14, Month 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60.
    • MoCA - screening, baseline, Day 14, Month 1, 3
    • Imaging - screening, baseline, Day 7, Day 14, Month 1, 3, 6, 9, 12, 15 18, 24, 30, 36, 48, 60.
    E.5.2Secondary end point(s)
    • Change over time in levels of AMT-130-derived vector DNA and miRNA expression in the CSF.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Baseline, then post treatment at 4, weeks, 13 weeks , 6 months, 9months, 12 months, 15 months, 18 months , and then every 6 months for total of 5 years.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase Ib/II
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Poland
    Germany
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 15
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 15
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-04-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-09-13
    P. End of Trial
    P.End of Trial StatusOngoing
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