Primary Objective:To evaluate recovery in patients with moderate COVID-19 after administration of SNG001 compared to placebo.Secondary Objectives:a. To evaluate the efficacy of SNG001 compared to placebo in patients with moderate COVID-19, using a…
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Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints:
a. Time to hospital discharge, defined by the OSCI score of 2 or below, with no
rebound at subsequent assessments.
b. Time to recovery, where recovery is defined as the OSCI score of 1 or below,
with no
rebound at subsequent assessments.
Secondary outcome
Key Secondary Endpoints:
a. Progression to severe disease or death, defined by the OSCI score of 5 or
above within 35 days of first dose (or randomization date if the patient not
dosed).
b. Progression to intubation or death, defined by the OSCI score of 6 or above
within 35 days of first dose (or randomization date if the patient not dosed).
c. Death within 35 days of first dose (or randomization date if the patient not
dosed).
Secondary Endpoints:
d. Recovery, where recovery is defined as the OSCI score of 1 or below, with no
rebound at subsequent assessments, at Days 7, 14, 21 and 28.
e. Hospital discharge by Days 7, 14, 21 and 28.
f. Improvement across the entire OSCI by Days 7, 14, 21 and 28.
g. Changes in breathlessness, cough and sputum scale (BCSS) score during the
study period, including disaggregated breathlessness and cough scores.
h. Changes in National Early Warning Score 2 (NEWS2) during the hospitalisation
period.
i. Daily assessment of COVID-19 symptoms and limitation of usual activities.
j. Quality of life measured using EQ-5D-5L.
k. Long-COVID-19 symptoms.
l. Safety and tolerability - vital signs, AEs concomitant medications, and
immunogenicity.
Background summary
Background:
Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is a global threat
and there is a need to assess new treatments which will prevent and effectively
treat severe lower respiratory tract (LRT) illness caused by the SARS-CoV-2.
Interferon beta (IFN-f3) has showed antiviral activity against SARS-CoV-2 in
cell-based assays (1). IFN-f3 driven anti-viral responses have been shown to be
compromised/deficient in older people (2) and those with chronic airways
diseases (3, 4). These, and other patient groups are at high risk of developing
severe LRT illness which can be fatal (5). The IFN-f3 deficiency can be
overcome through the administration of exogenous IFN-f3. This has been shown
both in vitro, using cells from patients, and in clinical trials using SNG001
(an inhaled IFN-f31a formulation for nebulisation). We hypothesise that SNG001
will rectify the deficiency in the lungs in at-risk patients and prevent severe
LRT illness in the context of SARS-CoV-2 infection.
The SG016 hospital pilot study was completed in May 2020. During this pilot
study, 101 hospitalised adults, >=18 years of age, with confirmed or suspected
SARS-CoV-2 infection were randomised to receive SNG001 or placebo. Results of
the pilot study showed that the risks of developing severe COVID-19 (the
disease caused by SARS-CoV-2) were markedly reduced in patients receiving
SNG001 compared to placebo and additionally that patients who received SNG001
were more than twice as likely to recover from COVID-19 as those on placebo. In
addition, there was a significant reduction in breathlessness in patients
receiving SNG001, compared to placebo (6).
SNG001 has been well tolerated in all clinical studies to date. Around 280
patients have been treated with SNG001. Of the 280, approximately 50 had
chronic obstructive pulmonary disease (COPD), 50 had confirmed COVID-19 with
varying underlying diseases i.e. heart disease, lung disease, diabetes etc and
the remaining 168 had asthma. The majority of the 280 patients had or were
suspected to have an active respiratory viral infection (rhinovirus, influenza,
coronavirus, SARS-CoV-2, etc) at the time of randomisation.
SNG001 is pH neutral, rather than acidic and does not contain excipients such
as mannitol, human serum albumin (HSA) and arginine, which are present in the
injectable IFN-f3 formulations and which may have their own unwanted effects if
delivered to the lungs.
SNG001 has historically been delivered using the I-neb, a mesh nebuliser made
by Philips Respironics. The I-neb has been tested to ensure the drug retains
its activity after aerosolization. A dose escalating trial established a target
lung dose which induced an antiviral response in the lungs that was present 24
hours after dose administration.
In this trial the Aerogen Ultra device will be used. The Ultra is mesh
nebuliser that is widely available and is better suited to single patient usage
in the hospital setting. Laboratory assessments found that both the I-neb and
the Ultra had similar levels of protein content in and similar IFN-f3 activity
post nebulisation.
The primary endpoint is recovery in patients with confirmed SARS-CoV-2
infection who are hospitalised due to moderate COVID-19, after administration
of SNG001 compared to placebo, where moderate COVID-19 is defined as presence
of clinical signs and symptoms necessitating administration of oxygen therapy
by mask or nasal prongs and recovery is defined as no limitation of activities
according to the Ordinal Scale of Clinical Improvement (OSCI), with no rebound
at subsequent assessments. The OSCI to be used in this trial is the 18th
February 2020 version as recommended by the World Health Organization (WHO)
(7).
Study objective
Primary Objective:
To evaluate recovery in patients with moderate COVID-19 after administration of
SNG001 compared to placebo.
Secondary Objectives:
a. To evaluate the efficacy of SNG001 compared to placebo in patients with
moderate COVID-19, using a range of endpoints.
b. To assess the general safety and tolerability of SNG001 compared to placebo
when administered to patients with moderate COVID-19.
Study design
Study Design:
Eligible patients will be randomised in a 1:1 ratio to receive SNG001 two
syringes or placebo two syringes.
Patients who had positive virus test for SARS-CoV-2 prior to hospitalisation
will be randomised no later than 48 hours after hospital admission. If the
virus test was performed more than 96 hours prior to hospitalisation, the test
will have to be repeated in the hospital prior to randomisation. Only patients
whose repeated virus test is positive will be randomised, no later than 48
hours after confirmation of SARS-CoV-2 infection.
Patients who had positive virus test for SARS-CoV-2 after hospitalisation will
be randomised no later than 48 hours after confirmation of SARS-CoV-2 infection.
SNG001 or placebo will be administered via the Ultra nebuliser. Patients will
receive a dose of SNG001 or placebo once a day for 14 days and will be followed
up for up to 90 days after completion of study medication (or randomization
date if the patient not dosed). Study data will be collected from patients
daily, as per the study schedule. Efficacy will be determined though
differences between the groups in the OSCI scores, and the secondary endpoints.
Adverse events (AEs) and concomitant medications will be monitored throughout
the study period.
A Data Safety Monitoring Committee (DSMC) will perform a review of the safety
data before 100 patients complete study treatment, to ensure the safety of
study patients. The DSMC will also meet as and when necessary, i.e. if a safety
issue arises or when the DSMC requests a further meeting.
Intervention
The treatments
If the patient qualifies to take part in this study, he/she will be assigned to
one of 2 treatment groups. For this study, we will have 2 groups:
• Treatment group 1 will receive the study drug SNG001.
• Treatment group 2 will receive the placebo.
Patients will be required to take study medication or placebo once a day for 14
days. Patients will have to inhale the study medication through a mouthpiece
that is connected to a nebuliser. Patients will need to take the study
medication at about the same time every day, ensuring that there is at least 8
hours between doses.
Study burden and risks
Avonex is the name of one of the interferon β drugs, a type of drugs, that is
given by injection to patients with multiple sclerosis. Avonex works similar to
SNG001. The only difference is that SNG001 is taken by inhalation and Avonex is
taken by injection. The side effects of interferon β (Avonex) when it is given
as an injection may be different in type, frequency and severity compared to
SNG001 that is being given via inhalation. Some of SNG001 will go through the
lungs into the bloodstream, this is normal. However, compared to blood levels
found after interferon β injection, the blood levels after inhalation would be
much lower and not detectable in most patients, and this will reduce the chance
of the side effects in this list.
This list describes the side effect profile of interferon β (Avonex) taken from
the medicines European product safety label that would be relevant to inhaled
SNG001.
Very common: more than 1 out of 10 subjects treated
• Flu like symptoms - muscle aches, chills or fever, sweating, lack of energy,
headache and feeling sick (nausea)
Common: 1 to 10 out of 100 subjects treated
• Loss of appetite
• Feeling weak and tired
• Difficulty sleeping
• Depression
• Flushing
• Runny nose
• Diarrhoea (loose stools)
• Feeling or being sick (nausea or vomiting)
• Numbness
• Rash, injection site pain, bruising or redness of the skin
• Increased sweating, night sweats
• Pain in your muscles, joints, arms, legs or neck
• Muscle cramps, stiffness in the joints and muscles
• Changes to blood tests (white cells/haematocrit/potassium and urea nitrogen)
• Symptoms you might not notice are tiredness, repeated infection, unexplained
bruising or bleeding
The risks of interferon β when given via injection are well known, but the full
risks of inhaling interferon β are not yet known. No safety concerns were
raised in previous studies when this drug was inhaled by asthmatics, patients
with chronic obstructive pulmonary disease (either in a stable state, when they
had a cold or a worsening of disease) and the most recent study in patients
with COVID 19 treated with inhaled SNG001. There were no significant changes
in the results of safety tests performed in these studies.
Administration of medications by nebuliser may cause local irritation such as
cough, wheezing or sore throat.
As with other medications, people treated with interferon β may be at risk of
developing allergic reactions or anaphylaxis. Symptoms of an allergic reaction
generally include overall body itching, hives (a sort of rash), skin flushing
or rash. Anaphylaxis is a more serious allergic reaction that may involve
dizziness, vomiting, low blood pressure and difficulty breathing. No cases of
anaphylaxis have been reported in patients treated with SNG001 in completed
clinical studies.
This list describes the uncommon and rare side effect profile of interferon β
(Avonex) taken from the medicines European product safety label that would be
relevant to inhaled SNG001.
Uncommon: (less than 1 in 100 people affected)
• Hair loss
• Reduction in platelet count (cell in the blood)
• Changes to your monthly period (female patients only)
Rare: (less than 1 in 1000 people affected)
• Difficulty breathing
• Rare clotting disorder of the blood
• Rare kidney disorders
Potential risks of the study procedures:
Blood Samples: Blood samples will be taken from a vein in the patient's arm
during the study. The taking of a blood sample may cause some discomfort and
bruising and there is a potential for infection. Other risks of taking blood,
although rare, include nerve damage, dizziness and fainting.
Blood pressure and heart rate: An inflatable cuff will be placed on the
patient's arm and a machine will measure his/her blood pressure and heart rate,
after he/she have been sitting down for 10 minutes. He/she may experience mild
discomfort in his/her arm while the cuff is inflated.
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Listed location countries
Age
Inclusion criteria
1. Male or female, >=18 years of age at the time of consent.
2. Admitted to hospital due to the severity of their COVID-19.
3. Positive virus test for SARS-CoV-2 using a validated molecular assay or
antigen assay. Patients who had positive virus test for SARS-CoV-2 prior to
hospitalisation will be randomised no later than 48 hours after hospital
admission. If the virus test was performed more than 96 hours prior to
hospitalisation, the test will have to be repeated in the hospital prior to
randomisation. Only patients whose repeated virus test is positive will be
randomised, no later than 48 hours after confirmation of SARS-CoV-2 infection.
Patients who had positive virus test for SARS-CoV-2 after hospitalisation will
be randomised no later than 48 hours after confirmation of SARS-CoV-2 infection.
4. Require oxygen therapy via nasal prongs or mask (OSCI score of 4).
5. Provided informed consent.
6. Female patients must be >=1 year post-menopausal, surgically sterile, or
using a highly effective method of contraception. Acceptable highly effective
methods of contraception include;
• bilateral tubal occlusion
• intrauterine device (provided coils are copper-banded)
• levonorgestrel intrauterine system (e.g., Mirena*)
• medroxyprogesterone injections (e.g., Depo-Provera*)
• etonogestrel implants (e.g., Implanon*, Norplan*)
• normal and low dose combined oral pills
• norelgestromin/ ethinylestradiol transdermal system
• intravaginal device (e.g., ethinylestradiol and etonogestrel), desogestrel
(e.g., Cerazette*)
• total sexual abstinence (defined as refraining from heterosexual intercourse)
• vasectomised sexual partner.
Women should have been stable on their chosen method of birth control for a
minimum of 3 months before entering the trial and should continue with birth
control for 1 month after the last dose of inhaled IFN-β1a/matching placebo. In
addition to the highly effective method of contraception (except for the
practice of total sexual abstinence), a condom (in UK with spermicides) should
be used by the male partner for sexual intercourse from randomisation (Visit 2)
and for 1 month after the last dose of inhaled IFN-β1a/matching placebo to
prevent pregnancy.
7. Women not of childbearing potential are defined as women who are either
permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy), or who are postmenopausal. Women will be considered
post-menopausal if they have been amenorrhoeic for 12 months prior to the
planned date of randomisation without an alternative medical cause. The
following age specific requirements apply:
• Women <50 years old would be considered post-menopausal if they have been
amenorrhoeic for 12 months or more following cessation of exogenous
hormonal treatment and if follicle stimulating hormone (FSH) levels are in the
postmenopausal range.
• Women >=50 years old would be considered post-menopausal if they have been
amenorrhoeic for 12 months or more following cessation of all exogenous
hormonal treatment.
If, in the setting of the pandemic, the use of an acceptable birth control
method is not possible, the decision to enrol a woman of childbearing potential
should be based on the benefit-risk for the patient, which should be discussed
with the patient at the time of the informed consent.
Exclusion criteria
1. Evidence of ongoing SARS-CoV-2 infection for more than 3 weeks, confirmed by
a validated molecular assay or validated antigen assay.
2. Non-invasive ventilation or high-flow oxygen (OSCI score of 5).
3. Mechanical ventilation (continuous or intermittent CPAP or intubation) or
admission to intensive care (OSCI score of >= 6).
4. Previous SARS-CoV-2 infection confirmed by a validated molecular assay or
validated antigen assay.
5. Any condition, including findings in the patients* medical history or in the
pre-randomisation study assessments that in the opinion of the Investigator,
constitute a risk or a contraindication for the participation of the patient
into the study or that could interfere with the study objectives, conduct or
evaluation.
6. Participation in previous clinical trials of SNG001.
7. Current or previous participation in another clinical trial where the
patient 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.
8. Inability to use a nebuliser with a mouthpiece.
9. Inability to comply with the requirements for storage conditions of study
medication in the home setting.
10. History of hypersensitivity to natural or recombinant IFN-β or to any of
the excipients in the drug preparation.
11. Females who are breast-feeding, lactating, pregnant or intending to become
pregnant.
12. Previous SARS-CoV-2 vaccination.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-004743-83-NL |
| CCMO | NL76537.075.21 |