Clinical trial NCT04669015: Phase 3 Inhaled Novaferon Study in Hospitalized Patients With Moderate to Severe COVID-19
Official title: NOVATION-1: A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate the Safety and Efficacy of Aerosolized Novaferon + SOC vs. Placebo + SOC in Hospitalized Adult Patients With Moderate to Severe COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Covid19
Keywords: antiviral
SARS-CoV-2
COVID19
Lead sponsor: Genova Inc.
Sponsor class: INDUSTRY
First posted: 2020-12-16
Enrollment: 914
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, double-blind, multicenter, placebo-controlled trial to evaluate the safety and efficacy of a novel therapeutic agent, Novaferon, in hospitalized adult patients diagnosed with COVID-19. The study is comprised of two cohorts:

* Cohort A: This is a blinded safety lead-in comprising two arms. 40 patients will be randomized on a 1:1 basis to receive either Novaferon or matched placebo via a commercial nebulizer, plus Standard of Care (SOC)
* Cohort B: This is the main portion of the study, which comprises two arms. Up to 874 patients will be randomized on a 1:1 basis to receive either Novaferon or matched placebo via a commercial nebulizer, plus SOC


Eligibility criteria: Inclusion Criteria:

Inclusion Criteria:

1. Signed informed consent form by any patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representatives prior to initiation of any study procedures.
2. Men and women, ≥18 years of age at time of enrollment.
3. Laboratory-confirmed diagnosis of SARS-CoV-2 infection as determined by PCR, or other health authority-approved commercial assay or other validated public health assay in any specimen within 72 hours prior to randomization (point-of-care viral infection test allowable if RT-PCR test result not available only at the time of screening).
4. Less than or equal to 9 days from COVID-19 symptom onset to starting treatment.

   • Symptoms are defined as one or more of the following: cough, fever, shortness of breath, chest pain, abdominal pain, nausea/vomiting, diarrhea, body aches, weakness/fatigue, chills/sweating, headache, confusion, sore throat, runny nose/congestion, loss of taste or smell, or any other COVID-19 symptoms as determined by the Investigator.
5. Hospitalized and i) requiring supplemental oxygen by face mask or nasal prongs, or ii) non-invasive ventilation or iii) high-flow oxygen (WHO category 4 or 5)
6. Female patients participating in this study must agree to avoid becoming pregnant and have a negative pregnancy test prior to randomization. Male and female patients of reproductive potential must use a highly effective, protocol-specified method of contraception during the study and up to post 30 days after the last dose of study drug. For a list of protocol-specified contraceptive methods, and the definition of reproductive potential, refer to Appendix 1.

Exclusion Criteria:

Exclusion Criteria:

1. Known hypersensitivity or intolerance to Interferon (IFN) or Novaferon or any excipient(s) of Novaferon, including pre-existing allergy or hypersensitivity to ampicillin.
2. Currently undergoing invasive mechanical ventilation (including venous ECMO).
3. Inability to use a nebulizer with a mouthpiece.
4. ALT/AST \> 5 times the Upper Limit of Normal (ULN) or a history of decompensated cirrhosis.
5. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR \< 30 mL/min/ 1.73m2).
6. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 48 - 72 hours, irrespective of the provision of treatment.
7. In the opinion of the Investigator, progression to mechanical ventilation is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment.
8. Possibility of the patient being discharged from hospital within 24 hours.
9. Concurrent participation in other anti-COVID-19 therapeutic or interventional trials. Patients may, at the discretion of the Investigator, concurrently participate in other non-interventional COVID-19 studies.
10. Prior or concurrent use of experimental antiviral therapy for COVID-19 (see Appendix 2.
11. Prior or concurrent use of any interferons other than the investigational product (see Appendix 2)
12. Other known active infections or other clinical conditions (e.g., severe chronic obstructive pulmonary disease) that contraindicate aerosolized inhalation.
13. Patients with current or prior psychiatric illness, seizure disorders, retinal autoimmune disorders, pre-existing severe cardiovascular disease, or patients with prior transplants.
14. Females who are breast-feeding, lactating, pregnant or intending to become pregnant.
15. The subject has any medical condition that in the opinion of the investigator would compromise subject's safety or compliance with study procedures.

Primary outcomes:
measure: Rate of clinical deterioration
timeFrame: From enrollment to Day 28
Secondary outcomes:
measure: Rate of recovery
timeFrame: From enrollment to Day 28
measure: Hospital discharge rate
timeFrame: At Day 28
measure: Mortality rate
timeFrame: At Day 28
measure: Duration of hospitalization
timeFrame: Up to Day 28
measure: Adverse events
timeFrame: From first dose to Day 56
Other outcomes:
Locations:
city: Bahia Blanca
country: Argentina
facility: Hospital Interzonal General de Agudos Dr Jose Penna
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: CEMIC
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Clinica Adventista Belgrano
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Clinica Zabala
city: Cordoba
country: Argentina
facility: Hospital San Roque
city: Cordoba
country: Argentina
facility: Sanatorio del Salvador Privado S.A.
city: Cordoba
country: Argentina
facility: Sanatorio Privado Duarte Quiroz De Clinica Colombo SA
city: Rio Cuarto
country: Argentina
facility: Instituto Medico Rio Cuarto
city: Villa Regina
country: Argentina
facility: Clinica Central S.A.
city: Alegre
country: Brazil
facility: HCPA- Hospital de Clínicas de Porto Alegre
city: Barretos
country: Brazil
facility: Fundação PIO XII Hospital de Amor de Barretos
city: Campinas
country: Brazil
facility: Hospital Casa de Saúde Vera Cruz (Coordenador)
city: Criciúma
country: Brazil
facility: Hospital São José
city: Goiânia
country: Brazil
facility: Hospital das Clínicas UFG
city: Guarulhos
country: Brazil
facility: Hospital Geral Prof. Dr. Waldemar de Carvalho Pinto Filho de Guarulhos - BR TRIALS
city: Horizonte
country: Brazil
facility: Hospital Felício Rocho
city: Jaú
country: Brazil
facility: Centro de Pesquisas Clínicas da Fundação Doutor Amaral Carvalho
city: Natal
country: Brazil
facility: CePCLIN - Centro de Estudos e Pesquisas em Moléstias Infecciosas
city: Porto Alegre
country: Brazil
facility: Hospital São Luiz de Jabaquara
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericórdia de Porto Alegre
city: São Paulo
country: Brazil
facility: Hospital 9 de Julho
city: São Paulo
country: Brazil
facility: Hospital São Luiz de Jabaquara
city: Tatuí
country: Brazil
facility: Instituto de Moléstias Cardiovalsculares Tatuí Ltda
city: Volta Redonda
country: Brazil
facility: Lobus Centro de Pesquisa
city: Volta Redonda
country: Brazil
facility: Lóbus Centro de Pesquisa Clínica
city: London
country: Canada
facility: University Hospital - London Health Sciences Centre
city: London
country: Canada
facility: Victoria Hospital -London Health Sciences Centre
city: Vancouver
country: Canada
facility: St Paul's Hospital
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
city: Osorno
country: Chile
facility: Hospital Base Osorno
city: Santiago
country: Chile
facility: Hospital Sotero del Rio
city: Floridablanca
country: Colombia
facility: Fundacion Cardiovascular de Colombia - Instituto del Carazon Floridablanco
state: Santander
city: Barranquilla
country: Colombia
facility: Clinica de la Costa Ltda
city: Barranquilla
country: Colombia
facility: Fundacion Hospital Universidad del Norte
city: Floridablanca
country: Colombia
facility: Fundacion Oftalmologica
city: Medellín
country: Colombia
facility: Clinica SOMER
city: Villavicencio
country: Colombia
facility: Corporacion Clinica
city: Bali
country: Indonesia
facility: RS Universitas Udayana
city: Jakarta
country: Indonesia
facility: Royal Taruma Hospital
city: Padang
country: Indonesia
facility: M. Djamil Hospital
city: Yogyakarta
country: Indonesia
facility: Sardjito Hospital
city: Kericho
country: Kenya
facility: KEMRI Kericho
city: Kisumu
country: Kenya
facility: KEMRI/CGHR Siaya Clinical Research Annexe
city: Kisumu
country: Kenya
facility: Victoria Biomedical Research Institute
city: Nairobi
country: Kenya
facility: CREATES - Strathmore University Medical Centre
city: Nairobi
country: Kenya
facility: Kenyatta National Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Miri
country: Malaysia
facility: Hospital Miri
city: Petaling Jaya
country: Malaysia
facility: Sunway Medical Centre
city: Serdang
country: Malaysia
facility: HPUPM
city: Callao
country: Peru
facility: Centro Medico Naval Cirujano Mayor Santiago Tavara
city: Lima Cercado
country: Peru
facility: Hospital Nacional Arzobispo Loayza
city: Lima
country: Peru
facility: Hospital III Daniel Alcides Carrion - Red Essalud de Tacna
city: Lima
country: Peru
facility: Hospital Nacional Dos de Mayo
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre
city: Cape Town
country: South Africa
facility: Tread Research
city: Centurion
country: South Africa
facility: Johese Clinical Research: Unitas
city: Durban
country: South Africa
facility: Drs Sarvan and Moodley
city: George
country: South Africa
facility: TASK Eden
city: Johannesburg
country: South Africa
facility: MERC SiReN
city: Mthatha
country: South Africa
facility: Nelson Mandela Academic Clinical Research Unit (NeMACRU)
city: Pretoria
country: South Africa
facility: Into Research
city: Somerset West
country: South Africa
facility: Dr JM Engelbrecht Trial Site
city: Worcester
country: South Africa
facility: Clinical Projects Research SA (PTY) LTD
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Diyarbakir
country: Turkey
facility: Dicle University, Medical Faculty
city: Istanbul
country: Turkey
facility: Acibadem Atakent Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Kartal Lutfi Kirdar Research and Training Hospital
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Kayseri
country: Turkey
facility: Kayseri City Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
city: Konya
country: Turkey
facility: Selcuk Universitesi Selcuklu Tip Fakultesi Hastanesi
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
city: Trabzon
country: Turkey
facility: Karadeniz Tecnical Uni. Med. Fac.
city: Dnipro
country: Ukraine
facility: CI Dnipropetrovsk CCH #6 of DRC Dept of Therapy (with pulmonological beds) SI DMA of MoHU
city: Dnipro
country: Ukraine
facility: CNE CCH #16 of Dnipro City Council, DSMU, Ch of Intern Med #1
city: Ivano-Frankivsk
country: Ukraine
facility: CNE Ivano-Frankivsk Reg Clin Infectious Hospital of Ivano-Frankivsk Regional Council
city: Kharkiv
country: Ukraine
facility: CNE of Kharkov RC Reg Cl Infectious Hospital
city: Kremenchuk
country: Ukraine
facility: Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1"
city: Kyiv
country: Ukraine
facility: Kyiv Municipal Clinical Hospital #17 O. O. Bogomolets NMU
city: Mykolaiv
country: Ukraine
facility: City Hospital #1
city: Odesa
country: Ukraine
facility: City Clinical infectious Hospital
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Infectious Hospital Dept of Diagnostics HSEIU Ukrainian Medical Stomatolog
city: Rivne
country: Ukraine
facility: Municipal Non-Profit Enterprise Central City Hospital Of Rivne City Council
city: Vinnytsia
country: Ukraine
facility: CCH #1 Vinnytsia M.I.Pyrogov NMU Ch of Infectious Diseases
city: Zhytomyr
country: Ukraine
facility: CI Central City Hospital #1 of Zhytomyr
Study officials:
References: