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고전적 파브리병에서 AMT-191의 안전성, PK/PD 및 탐색적 효능 연구

2026년 9월 21일 업데이트: UniQure Biopharma B.V.

고전적 파브리병을 앓고 있는 성인 남성을 대상으로 한 정맥 AAV5-GLA(AMT-191)의 1/2상, 단일 용량, 용량 증량 연구

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.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

20

단계

  • 2 단계
  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

  • 이름: Christy Quintana, Director, Clinical Operations
  • 전화번호: 734-680-7773
  • 이메일: medinfo@uniqure.com

연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

남성

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 순차적 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 용량 범위 지정 코호트 1
의약품: 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.
실험적: 용량 범위 지정 코호트 2
의약품: 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.
실험적: 용량 범위 지정 코호트 3
의약품: 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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
기간
FD 참가자를 대상으로 다양한 용량 수준의 정맥 투여 AMT-191의 안전성과 내약성을 평가합니다.
기간: 60개월
60개월

2차 결과 측정

결과 측정
측정값 설명
기간
Characterize the vector shedding of intravenously-administered AMT-191
기간: 60 Months

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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

UniQure Biopharma B.V.

수사관

  • 연구 책임자: Arian Pano, MD, MPH, Clinical Development and Program Lead, uniQure biopharma, B.V.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2024년 6월 5일

기본 완료 (추정된)

2027년 12월 1일

연구 완료 (추정된)

2031년 11월 30일

연구 등록 날짜

최초 제출

2023년 12월 19일

QC 기준을 충족하는 최초 제출

2024년 2월 20일

처음 게시됨 (실제)

2024년 2월 21일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 24일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 21일

마지막으로 확인됨

2026년 9월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • CT-AMT-191-01

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다