4D-710 in Adult Patients With Cystic Fibrosis

Официальное название

An Open-label, Phase 1/2 Trial of Gene Therapy 4D-710 in Adults With Cystic Fibrosis

Обзор

This is a Phase 1/2 multicenter, open-label, single dose trial of 4D-710 investigational gene therapy in adults with cystic fibrosis.

Подробное описание

This Phase 1/2 trial will evaluate the safety, tolerability, and preliminary efficacy of 4D-710, an investigational gene therapy, in adults with cystic fibrosis (CF) lung disease who are ineligible or unable to tolerate CFTR modulator therapy. A sub-study will evaluate 4D-710 in a cohort of adults with CF advanced lung disease and/or frequent pulmonary exacerbation (PE) while on currently available CFTR modulator therapy.

Вмешательства

• Биопрепарат 4D-710
  4D-710 is an adeno-associated virus (AAV) gene therapy comprised of an AAV capsid variant (4D-A101) carrying a transgene cassette encoding human cystic fibrosis transmembrane conductance regulator with a deletion in the regulatory domain (CFTRΔR).

Первичные конечные точки

• Incidence and severity of adverse events [Срок оценки: 60 Months]

Критерии участия

Key Inclusion Criteria (Primary Study):

• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:

• Sweat chloride ≥ 60 mmol/L
• Mutation Status

• Bi-allelic mutations in the CFTR gene, or
• Single mutation in the CFTR gene and clinical manifestations of CF lung disease
• Ineligible for CFTR modulator therapy, or previously received modulator therapy but discontinued due to adverse effects.
• Forced expiratory volume in 1 second (FEV1) ≥ 50% and ≤ 90% of predicted (per Global Lung Function Initiative) at Screening
• Resting oxygen saturation ≥ 92% on room air at Screening

Key Inclusion Criteria (Sub-Study):

• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:

• Sweat chloride ≥ 60 mmol/L
• Mutation Status

• Bi-allelic mutations in the CFTR gene, or
• Single mutation in the CFTR gene and clinical manifestations of CF lung disease
• Currently on a stable dose of CFTR modulator therapy for a minimum of 60 days prior to Screening and agree to maintain current regimen through the 24-month Observation Period
• FEV1 ≥ 40% and < 70% predicted (per Global Lung Function Initiative) at Screening, AND/OR experienced at least 2 pulmonary exacerbations in the last year requiring intravenous antibiotics

Key Exclusion Criteria (Primary and Sub Study):

• Any prior gene therapy for any indication (Exception: mRNA-based or antisense oligonucleotide therapies are not exclusionary)
• Active Mycobacterium abscessus infection requiring ongoing treatment at Screening
• Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy
• Smoking (e.g. cigarettes, cigars, cannabis) or use of a vaping product during the 2 months prior to screening; must agree to not smoke or use vaping products during Screening and initial 24-month observation period.
• Contraindication to systemic corticosteroid therapy
• Requires chronic use of systemic corticosteroids or immunosuppressants to treat another condition
• If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes: Hemoglobin A1C ≥ 6.5% at Screening
• If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C > 7.5% at Screening
• Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per Investigator's assessment
• Other conditions that, in the Investigator's opinion, may interfere with management of corticosteroid-related hyperglycemia
• Body Mass Index (BMI) < 16
• Laboratory abnormalities at screening:

• ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN)
• Total bilirubin ≥ 2 × ULN
• Hemoglobin < 10 g/dL
• Requirement for continuous or night-time oxygen supplementation
• Known CF liver disease with evidence of multilobular cirrhosis
• History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 20 центров

• University of Alabama Child Health Research Unit — Birmingham
• The University of Arizona — Tucson
• University of California San Francisco — San Francisco
• National Jewish Health — Denver
• University of Florida — Gainesville
• University of Miami Hospital — Miami
• Northwestern Memorial Hospital — Chicago
• University of Kansas Medical Center — Kansas City
• … и ещё 12 центров

Публикации

• Calton MA, Croze RH, Sullivan TH, Collins SA, Tucker S, Whittlesey KJ, Kim DH, Nye JA, Beliakoff G, Quezada M, Burns C, Schmitt C, Klein A, Jia V, Kovacs L, Lauko D, Yoh K, Nguyen K, Barglow K, Gonzales J, Khoday D, Mason T, Delaria K, Bashour K, Kotterman M, Schaffer D, Song A, Francis P, Taylor-Cousar JL, Kirn D. Design and characterization of 4D-710, an aerosolized gene therapy for cystic fibro PMID 41124321

Идентификаторы

NCT: NCT05248230 · 4D-710-C001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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