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嚢胞性線維症患者におけるSPL84の安全性、忍容性、薬物動態、および予備有効性

2026年11月5日 更新者：SpliSense Ltd.

SPL84の安全性、忍容性、薬物動態、および予備有効性を評価するための、3849 +10 Kb C->T変異を持つ嚢胞性線維症患者を対象とした第2a相無作為化プラセボ対照二重盲検複数漸増用量試験

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.

調査の概要

状態

募集

条件

介入・治療

研究の種類

介入

入学 (推定)

64

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • California
      • Long Beach、California、アメリカ、90806
        • 募集
        • Memorial Care Long Beach Medical Center
        • コンタクト：
      • Los Angeles、California、アメリカ、90033
        • 募集
        • University of Southern California
        • コンタクト：
      • San Francisco、California、アメリカ、94143
        • 募集
        • University of California, San Francisco
        • コンタクト：
      • Santa Monica、California、アメリカ、90404
        • まだ募集していません
        • University of California Los Angeles
        • コンタクト：
    • Colorado
      • Denver、Colorado、アメリカ、80206
        • 募集
        • National Jewish Health
        • コンタクト：
    • Florida
      • Hollywood、Florida、アメリカ、33021
        • まだ募集していません
        • Joe DiMaggio Children's Hospital
        • コンタクト：
    • Illinois
      • Chicago、Illinois、アメリカ、60611
        • まだ募集していません
        • Northwestern University
        • コンタクト：
    • Massachusetts
      • Boston、Massachusetts、アメリカ、02115
    • Minnesota
      • Minneapolis、Minnesota、アメリカ、55455
        • まだ募集していません
        • University of Minnesota
        • コンタクト：
    • New York
      • New York、New York、アメリカ、10032
        • まだ募集していません
        • Columbia University Cystic Fibrosis Program
        • コンタクト：
      • New York、New York、アメリカ、10028
        • 募集
        • Lenox Hill Cystic Fibrosis Center
        • コンタクト：
    • North Carolina
      • Chapel Hill、North Carolina、アメリカ、27514
        • まだ募集していません
        • University of North Carolina at Chapel Hill
        • コンタクト：
    • Pennsylvania
      • Philadelphia、Pennsylvania、アメリカ、19104
    • Utah
      • Salt Lake City、Utah、アメリカ、84132
    • Virginia
      • Falls Church、Virginia、アメリカ、22042
        • まだ募集していません
        • Inova Fairfax Hospital
        • コンタクト：
    • Washington
      • Seattle、Washington、アメリカ、98195
        • 募集
        • University of Washington Medical Center
        • コンタクト：
          • Lauren Bartlett
          • 電話番号：+1(503) 583-2869
          • メール：lrejman@uw.edu
  • イスラエル
      • Jerusalem、イスラエル、91240
      • Petah Tikva、イスラエル、49100
        • 募集
        • Rabin Medical Center (Beilinson Hospital)
        • コンタクト：
  • イタリア
      • Milan、イタリア、20122
        • 募集
        • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
        • コンタクト：
  • スペイン
      • Barcelona、スペイン、08035
        • 募集
        • Vall d'Hebron Barcelona Hospital Campus
        • コンタクト：
  • チェコ
      • Prague、チェコ、150 06
        • まだ募集していません
        • Motol University Hospital
        • コンタクト：
  • ドイツ
      • Berlin、ドイツ、10117
        • 募集
        • Charité - Universitätsmedizin Berlin
        • コンタクト：
      • Potsdam、ドイツ、14467
        • 募集
        • Klinikum Westbrandenburg CF Zentrum Potsdam
        • コンタクト：
  • フランス
      • Montpellier、フランス、34295
        • 募集
        • Centre Hospitalier Régional Universitaire (CHRU) de Montpellier
        • コンタクト：
  • ポーランド
      • Poznan、ポーランド、60-569
        • まだ募集していません
        • Kliniki Pulmonologii, Alergologii i Onkologii Pulmonologicznej Uniwersytetu Medycznego im.Karola Marcinkowskiego w Poznaniu
        • コンタクト：
      • Rabka-Zdrój、ポーランド、34-700
        • まだ募集していません
        • Instytut Gruźlicy i Chorób Płuc Oddział Terenowy im. Jana i Ireny Rudników
        • コンタクト：
  • リトアニア
      • Kaunas、リトアニア、LT-50161
        • まだ募集していません
        • Hospital of Lithuanian University of Health Sciences Kaunas Clinics
        • コンタクト：
          • Virginija Kalinauskaitė-Žukauskė
          • 電話番号：+37068727371
          • メール：virgucee@gmail.com

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：順次割り当て
  • マスキング：ダブル

武器と介入

参加者グループ / アーム
介入・治療
プラセボコンパレーター：プラセボ
他の：Placebo

Placebo solution for nebulization
アクティブコンパレータ：SPL84
薬：SPL84

SPL84 solution for nebulization

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal heart rate
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)

二次結果の測定

結果測定
メジャーの説明
時間枠
Characterization of pharmacokinetics (PK) of SPL84: maximum serum concentration (Cmax)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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-∞)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：Day 1 through Day 87
Day 1 through Day 87
Efficacy of SPL84 as assessed by change from baseline in percent predicted FEV1
時間枠：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
時間枠：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
時間枠：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)
時間枠：Day 1 to Day 85

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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

SpliSense Ltd.

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2024年6月24日

一次修了 (推定)

2027年10月1日

研究の完了 (推定)

2027年12月31日

試験登録日

最初に提出

2024年5月15日

QC基準を満たした最初の提出物

2024年5月20日

最初の投稿 (実際)

2024年5月24日

学習記録の更新

投稿された最後の更新 (実際)

2026年11月10日

QC基準を満たした最後の更新が送信されました

2026年11月5日

最終確認日

2026年11月1日

詳しくは

本研究に関する用語

追加の関連 MeSH 用語

その他の研究ID番号

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

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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