This is an double-blind, randomized, placebo controlled phase III study in hospitalizedsubjects with confirmed SARS-CoV-2.
Recruitment SSubjects hospitalised or attended the hospital ED with a confirmed diagnosis
of SARS-CoV-2, will be contacted.
Potential subjects will have the opportunity to ask any questions to the researchers.
A member of the research team will provide a copy of the information sheet to the
subject, who will have the opportunity to ask any questions to the researchers.
Subjects expressing an interest in participating will be interviewed to explain the study
in detail, and discuss the risks, benefits, goals and limitations of the study.
Screening Procedures. Potentially eligible subjects will provide informed consent prior
to any study specific procedures being conducted.
Following the provision of informed consent, the subject's demographics and medical
history especially that relating to SARS-CoV-2 will be documented.
A physical examination and checks on vital signs (BP, pulse, temperature, respiration)
will be conducted. Female subjects of child-bearing potential will undergo a urine
pregnancy test. A blood sample will be drawn for routine haematology and biochemistry.
Subjects will undergo tests for oxygen saturation, PaO2/FiO2 and interleukin-6 (IL-6).
Subjects will be asked to provide details of any concomitant medications. Subjects with
confirmed diagnosis of SARS-CoV-2, compliance with the inclusion and exclusion criteria
and providing informed consent will be registered on the e-CRF to obtain a randomisation
number.
Baseline/Randomisation A physical examination and checks on vital signs (BP, pulse,
temperature, respiration) will be conducted. Subjects will undergo tests for oxygen
saturation, PaO2/FiO2 and interleukin-6. Haematology and biochemistry test (from
screening) results will be confirmed as being acceptable.
The study centre will dispense the IMP under blinded conditions according to a permuted
block randomisation sequence (1:1 ratio for the two subject groups).
The subjects will be trained on the dosing and asked to administer two capsules twice
daily for 4 weeks. Subjects will then be provided with IMP on a daily basis by a suitably
qualified and delegated member of the Investigator's team, for the duration of the
treatment phase.
Treatment Phase (Week 1-3) All subjects will receive standard of care treatment
throughout the treatment phase on a day to day basis. This will include assessment of
additional or alternative medication required for the treatment of SARS-CoV-2,
requirement for intubation and invasive ventilation, requirement to transfer to intensive
care unit or death.
On a weekly basis, a physical examination and checks on vital signs (BP, pulse,
temperature, respiration) will be conducted. Subjects will undergo tests for oxygen
saturation, PaO2/FiO2 and IL-6.
Subjects will be asked to provide details of any concomitant medications and changes in
condition via adverse event (AE) query.
Week 4 A physical examination and checks on vital signs (BP, pulse, temperature,
respiration) will be conducted. Subjects will undergo tests for oxygen saturation,
PaO2/FiO2 and IL-6. Female subjects of child-bearing potential will undergo a urine
pregnancy test. A blood sample will be drawn for routine haematology and biochemistry.
Subjects will be asked to provide details of any concomitant medications and changes in
condition via AE query.
Week 6 (Follow -up) 6 weeks after randomisation (or two weeks after early withdrawal),
the subject will be contacted to check the occurrence of any other adverse events and
review of medications. Haematology and biochemistry test (from week 4) results will be
confirmed as being acceptable.
Adverse events will be assessed by spontaneous reports by subjects.
Drug: Eicosapentaenoic acid gastro-resistant capsules
same as in arm/group description
Other Name: Alfa
Drug: Placebo
same as in arm/group description
Inclusion criteria:
The subject must satisfy the following criteria for entry into the study:
1. Male or female, aged 18 years and above.
2. Provide informed consent prior to any study specific procedure being conducted; for
older patients who lack mental or physical capacity, next of kin or legal guardians
will be allowed to provide consent on their behalf. This consent can be obtained
remotely by telephone to the next of kin, or by a doctor with relevant experience in
COVID-19 disease not directly involved in the study acting as the patient's advocate
and then subsequently informing the next of kin (eg by a telephone call also
offering them an opportunity to review and agree the ICF with them; the patient may
then continue in the study or withdraw at a later date if the next of kin
subsequently decides to withdraw consent).
3. Positive local approved test to confirm diagnosis of SARS-CoV-2 within 7 days prior
to baseline.
4. Classified as moderate or severe based on the modified WHO/NIH baseline severity
criteria. Moderate: evidence of lower respiratory disease by clinical assessment
(e.g. signs or symptoms of lung infection) or by chest X-ray/CT/ultrasound imaging
(e.g. viral pneumonia, lung infiltrates) and a saturation of oxygen (SaO2) ≥ 94% on
room air at sea level. Severe: respiratory frequency >30 bpm, SaO2 < 94% on room air
at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired
oxygen (PaO2/FiO2) < 300 mmHg, or lung infiltrates >50%.
5. Hospitalised or attended the hospital ED due to clinical and/or virological
diagnosis of SARS-CoV-2; subsequent follow up after screening may be carried out in
hospital (hospitalised) or at a COVID-19 hospital OP clinic as clinically indicated
at the investigator's discretion. Where it is not possible for the subject to attend
a hospital OP clinic, then providing a suitably trained healthcare professional (eg
part of the clinical research team) as directed by the investigator, is available to
visit the subject at home to conduct the necessary clinical and SaO2 assessments and
blood tests, subsequent assessments post-hospitalisation or ED visit may be
conducted at the subject's home.
Exclusion criteria:
The subject will be excluded from the study if any of the following applies:
1. No symptoms or signs or lung imaging abnormalities of SARS-CoV-2.
2. On or clinically diagnosed as requiring intubation at screening.
3. On or clinically diagnosed as requiring mechanical ventilation at screening.
4. On or clinically diagnosed as requiring oxygen delivered by high flow nasal cannula
(heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >
20 L/min with fraction of delivered oxygen ≥ 0.5).
5. On or clinically diagnosed as requiring noninvasive positive pressure ventilation.
6. On or clinically diagnosed as requiring extracorporeal membrane oxygenation (ECMO).
7. Unable to swallow study capsules easily.
8. Known allergic reaction or intolerant to fish or fish oils.
9. Known allergic reaction to excipients of IMP.
10. Pregnant or breast-feeding at screening.
11. Taking other fish-oil supplements (e.g. cod liver oil) who are unwilling to stop
them for the duration of the study.
12. Taking immunomodulators/immunosuppressants, including corticosteroids on entry into
the study.
13. Used another investigational drug in the past 48 hours or 5 half-lives, whichever is
longer, prior to Screening.
14. Participating in other clinical studies at the same time.
15. Evidence of multi-organ failure, SOFA score > 9.
16. Deemed, by the investigator, unlikely to be able to comply with the requirements of
the protocol.
17. Deemed, by the investigator, likely to require transfer to the intensive care unit
(ICU) or unlikely to survive for at least 48 hours.
18. Any gastro-intestinal symptoms at screening considered clinically significant.
19. Clinically significant abnormalities, which in the opinion of the investigator would
significantly risk the safety of the subject or the main objectives of the study.
Hospital Universitario Vall d'Hebron
Barcelona, Spain
Hull
Cottingham, United Kingdom
UHCW
Coventry, United Kingdom
NPH
Harrow, United Kingdom
Rotherham NHS Foundation Trust
Rotherham, United Kingdom
Justin Slagel
01923681001
jslagel@slapharma.com