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Étude d'innocuité, de pharmacocinétique/PD et d'efficacité exploratoire de l'AMT-191 dans la maladie de Fabry classique

21 septembre 2026 mis à jour par: UniQure Biopharma B.V.

Une étude de phase 1/2, à dose unique et à dose croissante d'AAV5-GLA intraveineuse (AMT-191) chez des hommes adultes atteints de la maladie de Fabry classique

The main goals of this clinical study are to characterize safety and PK/PD of AMT-191 i.e. if drug doses used in the study are safe and tolerable and to understand how it acts in the body of people with Fabry disease.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

In Fabry disease, the enzyme α-galactosidase A is deficient. AMT-191 is an investigational gene therapy that encodes a recombinant serotype 5 based adeno-associated viral vector (rAAV5). AMT-191 is designed to target the liver for production of the enzyme α-galactosidase A (αGAL). AMT-191 is delivered via a single (one-time) intravenous (IV) infusion.

In this first-in-human study of AMT-191, three dose levels will be tested. All eligible participants will receive AMT-191 at one of the dose levels; there is no placebo in this study. The starting dose level is decided based on accepted rules for dose translation from preclinical (animal) studies to humans. Subsequent dose cohort levels are decided based on the review of safety, tolerability, and PK/PD results by an Independent Data Monitoring Committee and in agreement with the Sponsor.

Participants will be monitored through study site visits, blood tests, imaging questionnaires, and other assessments as per the study protocols.

Type d'étude

Interventionnel

Inscription (Estimé)

20

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

  • Nom: Christy Quintana, Director, Clinical Operations
  • Numéro de téléphone: 734-680-7773
  • E-mail: medinfo@uniqure.com

Lieux d'étude

  • États-Unis
    • Alabama
      • Birmingham, Alabama, États-Unis, 35233
        • Recrutement
        • The Kirklin Clinic Of University of Alabama Birmingham Hospital
        • Contact:
        • Chercheur principal:
          • Eric Wallace, MD
    • California
      • Los Angeles, California, États-Unis, 90095
        • Recrutement
        • University of California Los Angeles (UCLA)
        • Chercheur principal:
          • Nicola Longo, MD
        • Contact:
    • Georgia
      • Atlanta, Georgia, États-Unis, 30322
        • Recrutement
        • Emory University School of Medicine
        • Chercheur principal:
          • William Wilcox, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, États-Unis, 60611
        • Recrutement
        • Ann & Robert H. Lurie Children's Hospital of Chicago
        • Chercheur principal:
          • Carlos E Prada, MD
        • Contact:
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, États-Unis, 55455
        • Recrutement
        • MHealth Fairview University of Minnesota Medical Center East Bank
        • Contact:
        • Contact:
        • Chercheur principal:
          • Chester B Whitley, MD
    • New York
      • New York, New York, États-Unis, 10029
        • Recrutement
        • NYC Health + Hospitals/Metropolitan
        • Chercheur principal:
          • Maryam Banikazemi
        • Contact:
    • Ohio
      • Cincinnati, Ohio, États-Unis, 45229
        • Recrutement
        • Children's Hospital Medical Center
        • Chercheur principal:
          • Robert J. Hopkin, MD
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, États-Unis, 15224
        • Recrutement
        • UPMC Children's Hospital of Pittsburgh
        • Contact:
        • Chercheur principal:
          • Damara Ortiz, MD
    • Utah
      • Salt Lake City, Utah, États-Unis, 84108
        • Recrutement
        • University of Utah, Clinical and Translational Sciences Institute
        • Contact:
        • Contact:
        • Chercheur principal:
          • Brian Shayota, MD, MPH
    • Virginia
      • Fairfax, Virginia, États-Unis, 22030
        • Recrutement
        • Lysosomal & Rare Disorders Research and Treatment Center, Inc
        • Chercheur principal:
          • Ozlem Goker-Alpan
        • Contact:
          • Lauren Noll
          • Numéro de téléphone: (571) 732-4655
          • E-mail: LNoll@ldrtc.org
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 65 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Homme

La description

Key Inclusion Criteria:

  • Male of age ≥ 18 years and ≤65 years

  • Confirmed clinical diagnosis of classic Fabry disease (FD) defined as:

    1. Absent or minimal αGAL A enzyme activity < 1% of mean normal measured in plasma regardless of variant status; OR
    2. α-galactosidase A (GLA) pathogenic or likely pathogenic variant associated with classic FD phenotype identified on molecular genetic testing with plasma αGLA A enzyme activity below lower bound of the reference range (as measured at trough enzyme replacement therapy [ERT] levels).

  • eGFR ≥ 40 mL/min/1.73 m2

  • Participant agrees to use a condom during sexual intercourse with any female partner who could become pregnant

  • Suboptimal response after at least 12 months of enzyme replacement therapy (ERT) treatment. Suboptimal response is defined as plasma lyso-Gb3 ≥ 2.3 nanograms per milliliter (ng/mL) at Screening and one or both of the following:

    • Persistent moderate or severe neuropathic pain (intermittent or continuous) over a period of at least 3 months prior to consent
    • Presence of gastrointestinal symptoms (abdominal cramping, constipation, or diarrhea), reported by the Participant as moderate or severe and that are either persistent or occurring two or more times over the 12 weeks prior to consent

  • Weight ≤ 120 kilograms (kg) and ≥ 45 kg

  • Able and willing to provide informed consent

  • Agrees to have no vaccinations within 6 weeks prior to and 6 weeks after dosing with AMT-191 unless allowed by stud protocol

Key Exclusion Criteria:

  • Any allergic hypersensitivity reaction to ERT or infusion reaction in the 12 months prior to consent that was of severity grade 3 or above based on Common Terminology Criteria for Adverse Events (CTCAE v5.0) and required emergency intervention for hypertension/hypotension to stabilize blood pressure or hypoxia OR any other life-threatening complication.

  • Proteinuria, with random urine protein/creatinine ratio (rUPCR) ≥1 mg/mg at Screening

  • Any previous treatment with investigational drug within 3 months prior to first Screening assessment

  • Any previous treatment with gene therapy

  • Any anticipated participation in interventional studies for the treatment of FD

  • Current use of chaperone therapy such as migalastat (Galafold®)

  • Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin

  • Presence of chronic, active, or latent infection with hepatitis B or C, human immunodeficiency virus (HIV), or tuberculosis (TB) as assessed at the screening visit.

  • Active or ongoing infection or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, cardiovascular, hematological, GI, endocrine (such as diabetes mellitus with poor glycemic control), pulmonary, neurological, cerebral, or psychiatric disease, alcoholism, drug dependency, or any other psychological disorder that could, in the opinion of the Investigator, risk the safety of the Participant, or interfere with adherence to the protocol procedures or interpretation of results

  • Evidence of any liver disease, including hepatitis, fibrosis, cirrhosis of the liver, neoplastic lesion, or any known medical condition that could impact the intended transduction of the vector and/or expression and activity of the protein

  • History of kidney transplantation or currently on hemodialysis or peritoneal dialysis

  • Moderately severe to severe cardiovascular disease, history of stroke or transient ischemic attacks within 12 months prior to Screening, history of ventricular tachycardia, history of or detection of other significant arrhythmia during Screening; significant thromboembolic disease history; or history of thrombotic risk resulting in current use of anticoagulant/antiplatelet agents.

  • Uncontrolled hypertension, defined as systolic blood pressure >140 millimeters of mercury (mmHg) (inclusive) and/or diastolic blood pressure outside the range of 60 to 85 mmHg (inclusive) at Screening, confirmed on at least 2 repeated measurements

  • Patients taking blood pressure medication to control blood pressure or proteinuria (eg, angiotensin-converting enzyme [ACE] inhibitors and angiotensin II receptor blockers [ARBs]) and have been titrated to a stable dose for at least 3 months prior to Screening are allowed in the study.

  • Glycated hemoglobin (HbA1c) at Screening ≥7%

  • Contraindication to systemic corticosteroid therapy or immunosuppressive therapy

  • Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within 12 months prior to Screening

  • Screening laboratory values for renal and liver function that meet or exceed any of the following:

    1. Alanine transaminase (ALT) > 1.5 x upper limit of normal for the testing laboratory (ULN)
    2. Aspartate aminotransferase (AST) > 1.5 x ULN
    3. Total Bilirubin > ULN (except if this is caused by Gilbert disease)
    4. Alkaline phosphatase (ALP) > ULN
    5. Creatinine > 2 x ULN
    6. Direct bilirubin > ULN
    7. Albumin < 30 g/L
    8. Gamma-glutamyl transferase (GGT) > ULN
    9. Alpha-fetoprotein > 20 ng/mL unless cause is known and does not meet any other exclusion criteria

  • Screening laboratory values for hematologic and coagulation function that meet any of the following:

    1. Hemoglobin < lower limit of normal (LLN) (as per reference laboratory ranges)
    2. Platelet count < 150 x1000/μl
    3. International normalized ratio (INR) >1.1
    4. Soluble terminal complement complex (sC5b-9)>ULN

  • Significant anatomical abnormalities on renal ultrasound such as the presence of only 1 kidney, significant differences in kidney sizes between the right and left kidneys >1.5 centimeters (about 0.59 inch), or presence of kidney cysts

  • Pre-existing ocular disease and/or intraocular pressure >21 mmHg at Screening unless referred for formal ophthalmology review and cleared b ophthalmologist to commence prednisone

  • To be (re)-assessed on Day 0 prior to planned infusion:

    1. Active systemic bacterial, viral, or fungal infection
    2. ALT or AST ≥ 1.5 x ULN

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Cohorte 1 de détermination de la dose
Médicament: AMT-191

A recombinant serotype 5 based adeno-associated viral vector (AMT-191) for one-time intravenous (IV) administration will be investigated in this study. This recombinant AAV5-based vector contains a coding deoxyribonucleic acid (DNA) sequence for human α-galactosidase A.

Delivery of AMT-191 to the systemic circulation is expected to result in a therapeutic effect by promoting the liver expression of the lysosomal enzyme GLA in plasma levels in patients with Fabry disease.
Expérimental: Cohorte 2 de détermination de la dose
Médicament: AMT-191

A recombinant serotype 5 based adeno-associated viral vector (AMT-191) for one-time intravenous (IV) administration will be investigated in this study. This recombinant AAV5-based vector contains a coding deoxyribonucleic acid (DNA) sequence for human α-galactosidase A.

Delivery of AMT-191 to the systemic circulation is expected to result in a therapeutic effect by promoting the liver expression of the lysosomal enzyme GLA in plasma levels in patients with Fabry disease.
Expérimental: Cohorte 3 de détermination de la dose
Médicament: AMT-191

A recombinant serotype 5 based adeno-associated viral vector (AMT-191) for one-time intravenous (IV) administration will be investigated in this study. This recombinant AAV5-based vector contains a coding deoxyribonucleic acid (DNA) sequence for human α-galactosidase A.

Delivery of AMT-191 to the systemic circulation is expected to result in a therapeutic effect by promoting the liver expression of the lysosomal enzyme GLA in plasma levels in patients with Fabry disease.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Évaluer l'innocuité et la tolérabilité de différents niveaux de dose d'AMT-191 administré par voie intraveineuse chez les participants atteints de FD
Délai: 60 mois
60 mois

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Characterize the vector shedding of intravenously-administered AMT-191
Délai: 60 Months

Duration of vector deoxyribonucleic acid (DNA) shedding present in blood, saliva, feces, semen, and urine.
60 Months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

UniQure Biopharma B.V.

Les enquêteurs

  • Directeur d'études: Arian Pano, MD, MPH, Clinical Development and Program Lead, uniQure biopharma, B.V.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

5 juin 2024

Achèvement primaire (Estimé)

1 décembre 2027

Achèvement de l'étude (Estimé)

30 novembre 2031

Dates d'inscription aux études

Première soumission

19 décembre 2023

Première soumission répondant aux critères de contrôle qualité

20 février 2024

Première publication (Réel)

21 février 2024

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

24 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

21 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CT-AMT-191-01

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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