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Segurança, tolerabilidade, farmacocinética e eficácia preliminar de SPL84 em pacientes com fibrose cística

5 de novembro de 2026 atualizado por: SpliSense Ltd.

Um estudo de fase 2a, randomizado, controlado por placebo, duplo-cego de dose ascendente múltipla em pacientes com fibrose cística portadores da mutação C-> T de 3849 +10 Kb para avaliar segurança, tolerabilidade, farmacocinética e eficácia preliminar de SPL84

The goal of this clinical trial is to learn if drug SPL84 is safe for adult patients with cystic fibrosis (CF). It will also learn if the drug works to treat works to treat CF with a specific mutation (3849 +10kb C-->T).

The purpose of this research study is to test the safety and effectiveness of multiple doses of the study drug, SPL84.

Researchers will compare drug SPL84 to a placebo (a look-alike substance that contains no drug) to see if drug SPL84 is safe and if it works to treat CF. In cohorts 1-3, SPL84 will be tested as a monotherapy, and in Cohort 4, SPL84 will be tested in participants who are already stable on CFTR modulator therapy.

Participants will take drug SPL84 or a placebo by inhalation every week for 9 weeks (cohorts 1-3) or 12 weeks (cohort 4) and visit the clinic approximately weekly for checkups and tests.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Estimado)

64

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Alemanha
      • Berlin, Alemanha, 10117
        • Recrutamento
        • Charité - Universitätsmedizin Berlin
        • Contato:
      • Potsdam, Alemanha, 14467
        • Recrutamento
        • Klinikum Westbrandenburg CF Zentrum Potsdam
        • Contato:
  • Espanha
      • Barcelona, Espanha, 08035
        • Recrutamento
        • Vall d'Hebron Barcelona Hospital Campus
        • Contato:
  • Estados Unidos
    • California
      • Long Beach, California, Estados Unidos, 90806
        • Recrutamento
        • Memorial Care Long Beach Medical Center
        • Contato:
      • Los Angeles, California, Estados Unidos, 90033
        • Recrutamento
        • University of Southern California
        • Contato:
      • San Francisco, California, Estados Unidos, 94143
        • Recrutamento
        • University of California, San Francisco
        • Contato:
      • Santa Monica, California, Estados Unidos, 90404
        • Ainda não está recrutando
        • University of California Los Angeles
        • Contato:
    • Colorado
      • Denver, Colorado, Estados Unidos, 80206
        • Recrutamento
        • National Jewish Health
        • Contato:
    • Florida
      • Hollywood, Florida, Estados Unidos, 33021
        • Ainda não está recrutando
        • Joe DiMaggio Children's Hospital
        • Contato:
    • Illinois
      • Chicago, Illinois, Estados Unidos, 60611
        • Ainda não está recrutando
        • Northwestern University
        • Contato:
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02115
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos, 55455
        • Ainda não está recrutando
        • University of Minnesota
        • Contato:
    • New York
      • New York, New York, Estados Unidos, 10032
        • Ainda não está recrutando
        • Columbia University Cystic Fibrosis Program
        • Contato:
      • New York, New York, Estados Unidos, 10028
        • Recrutamento
        • Lenox Hill Cystic Fibrosis Center
        • Contato:
    • North Carolina
      • Chapel Hill, North Carolina, Estados Unidos, 27514
        • Ainda não está recrutando
        • University of North Carolina at Chapel Hill
        • Contato:
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19104
    • Utah
      • Salt Lake City, Utah, Estados Unidos, 84132
    • Virginia
      • Falls Church, Virginia, Estados Unidos, 22042
        • Ainda não está recrutando
        • Inova Fairfax Hospital
        • Contato:
    • Washington
      • Seattle, Washington, Estados Unidos, 98195
        • Recrutamento
        • University of Washington Medical Center
        • Contato:
          • Lauren Bartlett
          • Número de telefone: +1(503) 583-2869
          • E-mail: lrejman@uw.edu
  • França
      • Montpellier, França, 34295
        • Recrutamento
        • Centre Hospitalier Régional Universitaire (CHRU) de Montpellier
        • Contato:
  • Israel
      • Jerusalem, Israel, 91240
      • Petah Tikva, Israel, 49100
        • Recrutamento
        • Rabin Medical Center (Beilinson Hospital)
        • Contato:
  • Itália
      • Milan, Itália, 20122
        • Recrutamento
        • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
        • Contato:
  • Lituânia
      • Kaunas, Lituânia, LT-50161
        • Ainda não está recrutando
        • Hospital of Lithuanian University of Health Sciences Kaunas Clinics
        • Contato:
          • Virginija Kalinauskaitė-Žukauskė
          • Número de telefone: +37068727371
          • E-mail: virgucee@gmail.com
  • Polônia
      • Poznan, Polônia, 60-569
        • Ainda não está recrutando
        • Kliniki Pulmonologii, Alergologii i Onkologii Pulmonologicznej Uniwersytetu Medycznego im.Karola Marcinkowskiego w Poznaniu
        • Contato:
      • Rabka-Zdrój, Polônia, 34-700
        • Ainda não está recrutando
        • Instytut Gruźlicy i Chorób Płuc Oddział Terenowy im. Jana i Ireny Rudników
        • Contato:
  • Tcheca
      • Prague, Tcheca, 150 06
        • Ainda não está recrutando
        • Motol University Hospital
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Cohort 1-3:

Inclusion Criteria:

  • Diagnosis of CF and two CF causing mutations; 3849+10 Kb C->T mutation on one allele in the CF transmembrane conductance regulator (CFTR) gene (homozygote or compound heterozygote). Source documentation from a certified genetic laboratory is required.
  • Body mass index (BMI) of ≥ 17 kg/m2.
  • FEV1 40-90% predicted at screening.
  • Non-smokers or vapers for at least 180 days (6 months) prior to screening, per participant report.

Exclusion Criteria:

  • Use of Kalydeco, Orkambi, Symdeko/Symkevi or Trikafta/Kaftrio within 30 days of first dose with study intervention.
  • Use of any investigational drug (other than SPL84) or device within 30 days of first dose with study intervention.
  • Use of systemic steroids over 3 consecutive months in the last 6 months prior to screening, or use of systemic steroids in the last month prior to screening. Use of inhaled steroids above 1 mg.
  • Use of CF medications, e.g. inhaled antibiotics, dornase alfa (Pulmozyme), hypertonic saline and physiotherapy should be on stable regimen for the period 28 days prior to screening; those participants taking inhaled antibiotics for prophylaxis must be on a stable regimen of these drugs for at least 90 days prior to first dose with study intervention.
  • Any acute infection including acute upper respiratory or lower respiratory infections, pulmonary exacerbation, changes in therapy for pulmonary disease, or any non CF-related illness which results in the initiation of any new therapy within 14 days prior to first dose with study intervention.
  • Hemoptysis of greater than 30 mL within 90 days prior to Day 1, or hospitalization for hemoptysis within 6 months of first dose with study intervention.
  • Liver disease characterized by clinically significant cirrhosis and/or documented portal hypertension.
  • History of any organ transplantation.
  • Documented coronavirus disease (COVID-19) infection within 4 weeks prior to dosing.

Cohort 4:

Inclusion Criteria:

  • Diagnosis of CF and two CF causing mutations; 3849+10 Kb C->T mutation on one allele in the CF transmembrane conductance regulator (CFTR) gene (homozygote or compound heterozygote). Source documentation from a certified genetic laboratory is required.
  • Body mass index (BMI) of ≥ 17 kg/m2.
  • FEV1 40-80% predicted at screening.
  • Non-smokers or vapers for at least 180 days (6 months) prior to screening, per participant report.
  • Stable adherence to standard use of Trikafta/Kaftio or Alyftrek for at least 3 months, or Alyftrek for 1 month after switching from Trikafta/Kaftio, according to prescribing information.

Exclusion Criteria:

  • Previous participation in active arm of SPL84-002 study (Cohort 1-3)
  • Use of any investigational drug (other than SPL84) or device within 30 days of first dose with study intervention.
  • Use of systemic steroids over 3 consecutive months in the last 6 months prior to screening, or use of systemic steroids in the last month prior to screening. Use of inhaled steroids above 1 mg.
  • Use of CF medications, e.g. inhaled antibiotics, dornase alfa (Pulmozyme), hypertonic saline and physiotherapy should be on stable regimen for the period 28 days prior to screening; those participants taking inhaled antibiotics for prophylaxis must be on a stable regimen of these drugs for at least 90 days prior to first dose with study intervention.
  • Any acute infection including acute upper respiratory or lower respiratory infections, pulmonary exacerbation, changes in therapy for pulmonary disease, or any non CF-related illness which results in the initiation of any new therapy within 14 days prior to first dose with study intervention.
  • Hemoptysis of greater than 30 mL within 90 days prior to Day 1, or hospitalization for hemoptysis within 6 months of first dose with study intervention.
  • Liver disease characterized by clinically significant cirrhosis and/or documented portal hypertension.
  • History of any organ transplantation.
  • Documented coronavirus disease (COVID-19) infection within 4 weeks prior to dosing.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição sequencial
  • Mascaramento: Dobro

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador de Placebo: Placebo
Outro: Placebo

Placebo solution for nebulization
Comparador Ativo: SPL84
Medicamento: SPL84

SPL84 solution for nebulization

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal heart rate
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal respiratory rate
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal systolic and diastolic blood pressure
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal oximetry
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal temperature
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal hematology lab test results
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal biochemistry lab test results
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal urinalysis lab test results
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as evaluated by number of subjects with at least one treatment-related adverse event (AE) or serious adverse event (SAEs)
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

Incidence, nature, and severity of AEs and SAEs
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal electrocardiogram (ECG) parameters
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

using an ECG machine that automatically calculates heart rate and measure PR, QRS, QT, and QTc intervals
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal physical examination findings
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

Complete physical examinations include general appearance, head, ears, eyes, nose, throat, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal pulmonary function tests results
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

Pulmonary function tests will be performed according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) and forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75) will be measured
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal immunogenicity results
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

assessment of anti-SPL84 antibodies will be performed both in serum and sputum
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Characterization of pharmacokinetics (PK) of SPL84: maximum serum concentration (Cmax)
Prazo: Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Characterization of PK of SPL84: Time to Cmax (Tmax)
Prazo: Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Characterization of PK of SPL84: terminal elimination half-life (t1/2)
Prazo: Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Characterization of PK of SPL84: Area under the curve to the final sample (AUC0-t)
Prazo: Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Characterization of PK of SPL84: Area under the curve to infinity (AUC0-∞)
Prazo: Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Characterization of PK of SPL84: Apparent clearance (CL/F)
Prazo: Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
Characterization of excretion of SPL84: concentration of SPL84 in urine
Prazo: Day 1 through Day 87 (Cohort 1-3) or Day 85 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or Day 85 (Cohort 4)
Efficacy of SPL84 as assessed by change from baseline in percent predicted FEF25-75
Prazo: Day 1 to Day 87 (Cohort 1-3) or Day 108 (Cohort 4)
Day 1 to Day 87 (Cohort 1-3) or Day 108 (Cohort 4)
Efficacy of SPL84 as assessed by change from baseline in body weight
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Preliminary efficacy of SPL84 as assessed by change from baseline of antibiotic treatment (Cohort 1-3 only)
Prazo: Day 1 through Day 87
Day 1 through Day 87
Efficacy of SPL84 as assessed by change from baseline in percent predicted FEV1
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

Pulmonary function tests will be performed according to the ATS/ERS
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Efficacy of SPL84 as assessed by change from baseline in Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

The score for is standardized on a 0- to 100-point scale on which higher scores represent a higher quality of life
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Cohort 1-3: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal sputum microbiology results Cohort 4: Exploratory efficacy of SPL84 as assessed by number of participants with change in abnormal sputum microbiology result
Prazo: Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

Sputum microbiology will be performed with a microbiology based assay; organism growth will be identified.
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
Exploratory efficacy of SPL84 as assessed by number of participants with change in Lung Clearance Index at 2.5% of starting concentration (LCI2.5)
Prazo: Day 1 to Day 85

Measured using multiple breath washout (at select study sites only)
Day 1 to Day 85

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

SpliSense Ltd.

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

24 de junho de 2024

Conclusão Primária (Estimado)

1 de outubro de 2027

Conclusão do estudo (Estimado)

31 de dezembro de 2027

Datas de inscrição no estudo

Enviado pela primeira vez

15 de maio de 2024

Enviado pela primeira vez que atendeu aos critérios de CQ

20 de maio de 2024

Primeira postagem (Real)

24 de maio de 2024

Atualizações de registro de estudo

Última Atualização Postada (Real)

10 de novembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

5 de novembro de 2026

Última verificação

1 de novembro de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • SPL84-002
  • 2024-511184-28 (Número EudraCT)

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

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