Phase 2 Study of Inhaled SNG001 in Mechanically Ventilated Patients With Respiratory Viral Infection

Официальное название

A Phase 2, Two-part Study to Assess the Safety, Antiviral Biomarker Responses, and Efficacy of Inhaled SNG001 for the Treatment of Patients With a Confirmed Respiratory Virus Infection Undergoing Invasive Mechanical Ventilation

Обзор

The goal of this Phase 2 study is to assess about the safety, antiviral biomarker responses and efficacy of SNG001 when given to patients requiring invasive mechanical ventilation due to a respiratory virus infection. Its ability to speed up virus clearance and reduce mortality, compared with standard of care, will be studied. The study is split into two parts. All participants will receive standard of care in addition to SNG001 or placebo. In Part 1, the safety of SNG001 will be assessed. Participants of 50 years and older will receive study drug or placebo once a day for up to 14 days, whilst in hospital. In Part 2, the primary objective will be the efficacy of SNG001. Participants between 18 and 50 years with an immunocompromising condition and patients over 50 years (with or without an immunocompromising condition) will receive study drug once a day for up to 14 days, whilst in hospital.

Вмешательства

• Препарат SNG001
  SNG001 nebuliser solution is presented as a ready-to-use aqueous solution (neutral pH) in glass syringes containing 0.65 mL of drug product solution containing 12 MIU/mL of IFNβ 1a.
• Препарат Placebo
  The placebo nebuliser solution is presented in glass syringes containing 0.65 mL of solution containing the same formulation as the study medication but without IFNβ 1a (i.e., only the excipients of the SNG001 solution).

Первичные конечные точки

• Part 1: AE and SAE Severity [Срок оценки: Up to 28 days from randomisation]
• Part 2: All-cause mortality [Срок оценки: Within 28 days from randomisation]

Вторичные конечные точки (11)

• Part 2: AE and SAE severity [Срок оценки: Up to 42 days from randomisation]
• Part 2: Change in mSOFA from baseline [Срок оценки: Up to 14 days]
• Part 2: Time to Extubation [Срок оценки: Up to 28 days from randomisation]
• Part 2: Number of ventilator free days [Срок оценки: Up to 28 days from randomisation]
• Part 2: Duration of stay in ICU [Срок оценки: Up to 28 days from randomisation]
• Part 2: Duration of stay in hospital [Срок оценки: Up to 28 days from randomisation]
• Part 2: Change in OSCI from baseline [Срок оценки: Up to 28 days from randomisation]
• Part 2: Time to first negative virus test [Срок оценки: Up to 14 days from randomisation]
• Part 2: Change in IFNβ levels from baseline [Срок оценки: Up to 14 days from randomisation]
• Part 2: No organ support [Срок оценки: At 28 days from randomisation and at 28 days post final dose]
• Part 2: All Cause Mortality [Срок оценки: Within 28 days post final dose]

Критерии участия

Part 1 Inclusion Criteria:

To be eligible for randomisation into Part 1 of this study, each participant must fulfil the following criteria:

• Informed consent or legal representative's consent obtained.
• Patients ≥50 years of age at the time of consent.
• Patient admitted to the ICU and requiring invasive mechanical ventilation (IMV) due to a respiratory virus infection.
• Presence of Influenza A (Flu A), Influenza B (Flu B), respiratory syncytial virus (RSV), rhinovirus (RV), adenovirus, parainfluenza, human metapneumovirus (HMPV), or coronaviruses (including SARS-COV-2 and seasonal coronaviruses) in a nose swab sample, confirmed by a positive virus test using a Sponsor approved rapid POC test (e.g., reverse transcription polymerase chain reaction \[RT-PCR\]).
• Time from intubation to administration of first dose of study medication ≤48 hours.
• Women of childbearing potential must have a negative pregnancy test. For this study, women of childbearing potential are defined as women <55 years old.

Part 1 Exclusion Criteria:

A participant must not be randomised into Part 1 of the study if they meet any of the following criteria:

• Expected termination of IMV within 24 hours from the time of randomisation
• Life expectancy <24 hours.
• Liver failure (Child-Pugh C).
• Severe congestive heart failure (New York Heart Association \[NYHA\] IV).
• Receipt of lung transplant.
• Known or suspected active tuberculosis, or infection with other mycobacteria
• Known or suspected active systemic fungal infection.
• Anticipated transfer to another hospital which would prevent the participant from continuing in the study and completing protocol assessments.
• Need for long-term mechanical ventilation prior to ICU admission.
• Use of inhaled sedation.
• Presence of tracheostomy or laryngectomy.
• Requirement for airway pressure release ventilation mode.
• History of hypersensitivity to natural or recombinant IFNβ or to any of the excipients in the drug preparation.
• Any condition, including findings in the patient's medical history or in the pre-randomisation study assessments that in the opinion of the Investigator, constitute a risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
• Participation in previous clinical studies of SNG001.
• Current or previous participation in another clinical study where the participant has received a dose of an Investigational Medicinal Product (IMP) containing small molecules within 30 days or 5 half-lives (whichever is longer) prior to entry into this study or containing biologicals within 3 months prior to entry into this study.
• Known or suspected pregnancy.
• Females who are breast-feeding or lactating.
• Immunocompromising condition, including:

• Established acquired immune deficiency syndrome (AIDS) defined as a cluster of differentiation 4 (CD4) count <200 cells/microL, and/or the presence of any AIDS-defining condition;
• Haematological malignancy;
• Bone marrow transplantation; or
• Immunosuppressive therapy, including:
• Cancer therapy (e.g. chemo-, radio-, immuno-, hormone or other types of therapy), immune-cell depleting therapy, immunosuppressive therapy for autoimmune disorders, medications for prevention of organ transplantation rejection, administered within 6 months prior to randomisation; or
• Corticosteroids >20 mg of prednisone or equivalent per day administered continuously for >14 days prior to randomisation.
• Severe chronic lung disease requiring home oxygen therapy, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis.

Part 2 Inclusion Criteria:

To be eligible for randomisation into Part 2 of this study, each participant must fulfil the following criteria:

1.a Patients ≥18 and <50 years of age at the time of consent, with an immunocompromising condition, including:

• Solid tumour malignancy undergoing cancer therapy (e.g. chemo-, radio-, immuno-, hormone or other types of therapy);
• Haematological malignancy in remission, with or without maintenance therapy;
• Immunosuppressive therapy for autoimmune disease;
• Therapy for prevention of organ transplant rejection;
• Corticosteroids >20 mg of prednisone or equivalent per day, administered continuously for >14 days prior to randomisation or

• b Patients ≥50 years of age at the time of consent, with or without an immunocompromising condition (as defined above).
• Patient admitted to the ICU and requiring IMV due to a respiratory virus infection.
• Presence of Flu A, Flu B, RSV, RV, adenovirus, parainfluenza, HMPV, or coronaviruses (including SARS-COV-2 and seasonal coronaviruses) in a Lower Respiratory Tract sample, confirmed by a positive virus test using a Sponsor approved rapid POC test (e.g., RT-PCR).
• Time from intubation to administration of first dose of study medication ≤48 hours.
• Informed consent or legal representative's consent obtained.
• Women of childbearing potential must have a negative pregnancy test. For this study, women of childbearing potential are defined as women <55 years old.

Part 2 Exclusion Criteria:

A participant must not be randomised into Part 2 of the study if they meet any of the following criteria:

• Expected termination of IMV within 24 hours from the time of randomisation.
• Life expectancy <24 hours.
• Liver failure (Child-Pugh C).
• Severe congestive heart failure (NYHA IV).
• Receipt of lung transplant.
• Known or suspected active tuberculosis, or infection with other mycobacteria.
• Known or suspected systemic fungal infection.
• Immunocompromising condition, including:

• Haematological malignancy requiring induction or consolidation therapy within 3 months prior to randomisation;
• Bone marrow transplant within 6 months prior to randomisation;
• Solid organ transplant within 6 months prior to randomisation;
• Corticosteroids >75 mg of prednisone or equivalent per day, administered continuously for >7 days prior to randomisation;
• Methotrexate therapy at randomisation, if the indication is chemotherapy for cancer;
• Chimeric antigen receptor (CAR)-T cell therapy, administered within 3 months prior to randomisation;
• Ibrutinib or alemtuzumab, administered within 3 months prior to randomisation;
• Neutropenia <500/mm3 not due to sepsis;
• Clinical presentation consistent with severe bone marrow suppression or pancytopenia;pancytopenia;
• Established AIDS, defined as a CD4 count <200 cells/microL, and/or the presence of any AIDS-defining condition.
• Anticipated transfer to another hospital which would prevent the participant from continuing in the study and completing protocol assessments.
• Need for long-term mechanical ventilation prior to ICU admission.
• Use of inhaled sedation.
• Presence of tracheostomy or laryngectomy
• History of hypersensitivity to natural or recombinant IFNβ or to any of the excipients in the drug preparation.
• Any condition, including findings in the patient's medical history or in the pre-randomisation study assessments that in the opinion of the Investigator, constitute a risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
• Participation in previous clinical studies of SNG001.
• Current or previous participation in another clinical study where the participant has received a dose of an IMP containing small molecules within 30 days or 5 half-lives (whichever is longer) prior to entry into this study or containing biologicals within 3 months prior to entry into this study.
• Known or suspected pregnancy.
• Females who are breast-feeding or lactating.
• Severe chronic lung disease requiring home oxygen therapy, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 22 центра

• University of California - Davis — Sacramento
• Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center — Torrance
• NCH Pulmonary Critical Care — Naples
• Emory University — Atlanta
• Snake River Research, PLLC — Idaho Falls
• Northwestern University — Chicago
• Sinai-Grace Hospital — Detroit
• William Beaumont Hospital — Royal Oak
• … и ещё 14 центров

Великобритания · 20 центров

• Torbay Hospital — Paignton
• Aberdeen Royal Infirmary — Aberdeen
• Queen Elizabeth Hospital Birmingham — Birmingham
• Bradford Royal Infirmary — Bradford
• Royal Sussex County Hospital — Brighton
• Cardiff and Vale Hospital — Cardiff
• Glasgow Royal Infirmary — Glasgow
• Queen Elizabeth University Hospital — Glasgow
• … и ещё 12 центров

Франция · 12 центров

• Centre Hospitalier d'Argenteuil — Argenteuil
• Centre Hospitalier de Bourg-en-Bresse — Bourg-en-Bresse
• CHD Vendee — La Roche-sur-Yon
• CH Le Mans — Le Mans
• CHU de Lille — Lille
• CHU de Limoges - Hopital Dupuytren 1 — Limoges
• CHU de Nantes - Hotel-Dieu — Nantes
• HCL Centre Hospitalier Lyon Sud — Pierre-Bénite
• … и ещё 4 центра

Испания · 5 центров

• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Clinic Barcelona — Barcelona
• Hospital Universitari Mutua Terrassa — Barcelona
• Hospital Universitari de Bellvitge — Barcelona
• Hospital Universitario 12 de Octubre — Madrid

Бельгия · 4 центра

• Universitair Ziekenhuis Brussel — Brussels
• Ziekenhuis Oost-Limburg - Campus Sint-Jan — Genk
• Centre Hospitalier Régional de la Citadelle — Liège
• Centre Hospitalier Universitaire (CHU) de Liege — Liège

Нидерланды · 4 центра

• Ziekenhuis Gelderse Vallei — Ede
• Canisius-Wilhelmina Ziekenhuis (CWZ) — Nijmegen
• Ikazia Ziekenhuis — Rotterdam
• Universitair Medisch Centrum Utrecht — Utrecht

Идентификаторы

NCT: NCT06999603 · SG021 · 2024-520375-27-00 · U1111-1317-0525 · ISRCTN30482473

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗