Covid 19Phase 2IONICNCT04516915
IMU-838 and Oseltamivir in the Treatment of COVID-19
A Phase 2 study testing IMU-838 and Oseltamivir in people with Covid 19, run by University Hospitals Coventry and Warwickshire NHS Trust at 1 site in United Kingdom.
Trial summary
To evaluate whether time-to-improvement is significantly better in IMU-838 plus Oseltamivir (IONIC Intervention) and standard care vs. Oseltamivir and standard care in adult subjects with coronavirus disease (COVID-19) Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Covid 19
- What is being tested?
- IMU-838 and Oseltamivir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Jun 2020to 21 Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Male or non-pregnant female patients at least 18 years old 2. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection, either:
- Confirmed cases: prospective participants who test positive to a validated specific SARS-CoV-2 nucleic acid test or has the virus identified by electron microscopy or viral culture, as per local trust policy ≤ 7 days before randomisation.
- Probable/Suspected case: prospective participants who may have been in contact with a confirmed case of COVID-19, AND have mild to severe COVID-19 clinical symptoms AND radio-graphic evidence* of pulmonary infiltrates consistent with COVID-19 disease 3. Moderate to severe COVID-19 requiring hospitalisation defined as: a) Clinical status category 3-5 (inclusive) on the 7-point clinical status category scale as proposed by the World Health Organisation (WHO) master protocol: I. Category 3: hospitalized, no oxygen therapy II. Category 4: hospitalized, oxygen by mask or nasal prongs III. Category 5: hospitalized, non-invasive ventilation or high-flow oxygen *where routinely available, no tests will be requested for research purpose
Who cannot join
- Therapy Exclusion Criteria:
- Use of the following concomitant medications is prohibited at Screening Visit and throughout the duration of the trial:
- Use of Oseltamivir for more than 48 hrs prior to the first treatment dose
- Use of antiviral drugs (e.g. nucleoside analogue reverse-transcriptase inhibitors, protease inhibitors, etc.)
- History of long-term or concurrent use of mycophenolate mofetil, methotrexate exceeding 17.5 mg weekly
- Chloroquine or hydroxychloroquine
Show all 32Show fewer
- Any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad as well as uricosuric drugs such as probenecid
- Treatments for any malignancy, in particular irinotecan, paclitaxel, tretinoin, bosutinib, sorafinib, enasidenib, erlotinib, regorafenib, pazopanib and nilotinib
- Any drug significantly restricting water diuresis, in particular vasopressin and vasopressin analogues
- Use of rosuvastatin at daily doses higher than 10 mg
- Medical History of Concomitant Disease Exclusion Criteria
- Allergic or hypersensitivity to the IMU-838, Oseltamivir, or any of the ingredients
- Pregnant or breastfeeding or with intention to become pregnant during the study
- Participants who cannot take trial medication orally at presentation
- Undergoing active chemotherapy or radiotherapy.
- If the attending clinician believes that there is a specific contra-indication to the IONIC intervention.
- Patient has a medical or concomitant disease history preventing them from participating
- Critical patients whose expected survival time < 48-72 hours
- Evidence of pancytopenia or immunosuppression
- Any contraindication to Oseltamivir or standard of care
- Presence of the following laboratory values at Screening Exclusion Criteria
- Platelet count <100,000/mm³ (<100 x 109/L)
- Total bilirubin > 2 x ULN or ALT or GGT > 5 x ULN
- Elevated indirect (unconjugated) bilirubin >1.2 x ULN (i.e. >1.1 mg/dL)
- Serum uric acid levels at Screening Visit >1.2 x ULN (for women >6.8 mg/dL, for men >8.4 mg/dL)
- Renal impairment defined as estimated glomerular filtration rate ≤45 mL/min/1.73m²
- Decompensated liver cirrhosis (Child-Pugh score B and C)
- History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (New York Heart Association [NYHA] class 3 or 4)
- Cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. NYHA class 4: Cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
- History or presence of any major medical or psychiatric illness (such as severe depression, psychosis, bipolar disorder), history of suicide attempt, or current suicidal ideation, if any of those conditions in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol
- COVID-19 related exclusion criteria
- Participation in any other interventional clinical trial for an experimental treatment for COVID-19
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospital Coventry and Warwickshire NHS Trust
Coventry, West Midlands, CV22DX
About this study
Official title: Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination With Oseltamivir, in Adults With COVID-19
To evaluate whether time-to-improvement is significantly better in IMU-838 plus Oseltamivir (IONIC Intervention) and standard care vs. Oseltamivir and standard care in adult subjects with coronavirus disease (COVID-19)
Read the detailed description
The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [IONIC Intervention] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care.
At present, there are no known treatments for COVID-19. Whilst, the anticipated scale of the epidemic is such that hospitals, and particularly intensive care facilities, may be massively overstretched. As described by a few models of pandemic spread, up to 50% of the adult population may fall sick over a period of 8-12 weeks, of whom around 10% may require hospitalisation. This figure could imply nearly 2 million hospital admissions. Considering this scenario, therapies which may only have a moderate impact on survival or on hospital resources could be worthwhile.
Critically, the present trial design has been developed with consideration of the front-line hospital staff working within an overstretched care system in these unprecedented times. To minimise their burden the protocol is deliberately flexible so that it is suitable for a wide range of settings, allowing:
- a broad range of patients to be enrolled (patient pathway, disease stage or mode of diagnosis)
- Additional sub-studies may be added to provide more detailed information on side effects or sub-categorisation of patient types but these are not the primary objective and are not required for participation.
- To be able to include more sites: the investigators will initiate the trial as a single centre (UHCW) and more sites invited to participate according to the emerging evidence
- The investigator have included 'Exploratory and Secondary objectives' in the protocol however, in consideration of the circumstances the research activities will emulate investigations performed as per standard care/routines care to minimise any burden on the delivery teams.
This is a Phase 2b, randomised, parallel-group, open-label study to assess the efficacy and safety of an oral dose of IMU-838 (22.5 mg twice daily [45 mg/day]) plus Oseltamivir (75mg twice daily [150mg/day]) (IONIC Intervetion) or Oseltamivir alone (75mg twice daily) in hospitalised patients with COVID-19.
- Conditions
- Covid 19
- Being tested
- IMU-838, Oseltamivir
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMU-838Drug
Also called Intervention Arm
IMU-838 twice daily at 22.5mg doses for 14 days
OseltamivirDrug
Also called Control arm
Oseltamivir twice daily at 75mg doses for 14 days
| Study group | Role | What they receive |
|---|---|---|
| IMU-838 + Oseltamivir | Experimental | Loading dose of IMU-838 followed by 22.5mg BID plus Oseltamivir (75mg BID) for 14 days Receives: Drug: IMU-838; Drug: Oseltamivir |
| Oseltamivir | Active comparator | Oseltamivir (75mg BID) for 14 days Receives: Drug: Oseltamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate whether time-to-improvement is significantly better in IMU-838 plus Oseltamivir (IONIC Intervention) vs. Oseltamivir alone in adult subjects with COVID-19
Time-to-clinical improvement; defined as the time from randomisation to a 2-point improvement on the world health organizations 9-point ordinal scale (ranging from 0-8; 0 being no evidence of clinical infection and 8 being death), discharge from hospital, or death (whichever occurs first)
Measured: 14 days
Secondary outcomes (5)
To evaluate safety (number of adverse events) and tolerability (laboratory abnormalities) of IMU 838 + Oseltamivir vs. Oseltamivir alone in adult subjects with COVID-19.
Incidence of Adverse events (AEs) and serious adverse events (SAEs), including COVID-19 worsening and incidence of laboratory abnormalities (defined as a 1.5x increase in liver function test results (total protein, albumin, bilirubin, alkaline phosphotase and ALT) from screening).
Measured: 28 days
To determine the effects of IONIC Intervention on improvement of at least two points in clinical status scale (from 0 to 8; with 8 being no evidence of clinical infection and 8 being death)
Proportion of patients with two-point change on WHO ordinal scale at Day 7 and 28
Measured: 28 days
To assess the effects of IONIC Intervention vs. Oseltamivir on the need for invasive ventilation, renal replacement therapy or ECMO
Proportion of patients free of invasive ventilation, renal replacement therapy or ECMO at Day 7 and 14
Measured: 14 days
To assess the effects of IONIC Intervention vs. Oseltamivir on the length of hospital and intensive care unit (ICU) stay
To assess the effects of IONIC Intervention vs. Oseltamivir on the length of hospital and intensive care unit (ICU) stay
Measured: 28 days
To assess the effects of IONIC Intervention vs. Oseltamivir on the time from treatment initiation to death
Mortality at day 28 and time from treatment initiation to death
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2020
- Study start15 Jun 2020
- Primary completion20 May 2022
- Study completion21 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid 19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, Randomized, Parallel-Group, Open-Label Study
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Coventry and Warwickshire NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Immunic AG, University of Warwick, MODEPHARMA
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04516915
- Sponsor's protocol ID
- RA486120
- Acronym
- IONIC
- Status last verified
- Aug 2023
- First submitted
- 10 Aug 2020
- Last updated
- 22 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sharma K, Berry L, Vryonis E, Ali A, Lara B, Noufaily A, Parsons N, Bradley C, Haley B, Tabuso M, Arasaradnam RP. Prospective, randomised, parallel-group, open-label study to evaluate the effectiveness and safety of IMU-838, in combination with oseltamivir, in adults with COVID-19: the IONIC trial protocol. BMJ Open. 2022 Nov 17;12(11):e055205. doi: 10.1136/bmjopen-2021-055205.
PubMed 36396307
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination With Oseltamivir, in Adults With COVID-19
- ClinicalTrials.gov ID
- NCT04516915
- Acronym / sponsor ID
- IONIC / RA486120
- Conditions
- Covid 19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University Hospitals Coventry and Warwickshire NHS TrustUniversity, hospital or other
- Collaborators
- Immunic AG, University of Warwick, MODEPHARMA
- Study start
- 15 Jun 2020 (actual)
- Primary completion
- 20 May 2022 (actual)
- Study completion
- 21 Sep 2022 (actual)
- First posted
- 18 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate whether time-to-improvement is significantly better in IMU-838 plus Oseltamivir (IONIC Intervention) and standard care vs. Oseltamivir and standard care in adult subjects with coronavirus disease (COVID-19)
Detailed description
The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [IONIC Intervention] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care.
At present, there are no known treatments for COVID-19. Whilst, the anticipated scale of the epidemic is such that hospitals, and particularly intensive care facilities, may be massively overstretched. As described by a few models of pandemic spread, up to 50% of the adult population may fall sick over a period of 8-12 weeks, of whom around 10% may require hospitalisation. This figure could imply nearly 2 million hospital admissions. Considering this scenario, therapies which may only have a moderate impact on survival or on hospital resources could be worthwhile.
Critically, the present trial design has been developed with consideration of the front-line hospital staff working within an overstretched care system in these unprecedented times. To minimise their burden the protocol is deliberately flexible so that it is suitable for a wide range of settings, allowing:
- a broad range of patients to be enrolled (patient pathway, disease stage or mode of diagnosis)
- Additional sub-studies may be added to provide more detailed information on side effects or sub-categorisation of patient types but these are not the primary objective and are not required for participation.
- To be able to include more sites: the investigators will initiate the trial as a single centre (UHCW) and more sites invited to participate according to the emerging evidence
- The investigator have included 'Exploratory and Secondary objectives' in the protocol however, in consideration of the circumstances the research activities will emulate investigations performed as per standard care/routines care to minimise any burden on the delivery teams.
This is a Phase 2b, randomised, parallel-group, open-label study to assess the efficacy and safety of an oral dose of IMU-838 (22.5 mg twice daily [45 mg/day]) plus Oseltamivir (75mg twice daily [150mg/day]) (IONIC Intervetion) or Oseltamivir alone (75mg twice daily) in hospitalised patients with COVID-19.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, Randomized, Parallel-Group, Open-Label Study
| Arm | Type | Receives |
|---|---|---|
| IMU-838 + Oseltamivir | Experimental | Drug: IMU-838, Drug: OseltamivirLoading dose of IMU-838 followed by 22.5mg BID plus Oseltamivir (75mg BID) for 14 days |
| Oseltamivir | Active comparator | Drug: OseltamivirOseltamivir (75mg BID) for 14 days |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 1. Male or non-pregnant female patients at least 18 years old 2. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection, either:
Key exclusion criteria (32 listed)
- Use of the following concomitant medications is prohibited at Screening Visit and throughout the duration of the trial:
- Use of Oseltamivir for more than 48 hrs prior to the first treatment dose
- Use of antiviral drugs (e.g. nucleoside analogue reverse-transcriptase inhibitors, protease inhibitors, etc.)
- History of long-term or concurrent use of mycophenolate mofetil, methotrexate exceeding 17.5 mg weekly
- Chloroquine or hydroxychloroquine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMU-838Also: Intervention ArmIMU-838 twice daily at 22.5mg doses for 14 days | Drug | IMU-838 + Oseltamivir |
| OseltamivirAlso: Control armOseltamivir twice daily at 75mg doses for 14 days | Drug | IMU-838 + Oseltamivir, Oseltamivir |
Primary outcome
To evaluate whether time-to-improvement is significantly better in IMU-838 plus Oseltamivir (IONIC Intervention) vs. Oseltamivir alone in adult subjects with COVID-19
Time frame: 14 days
Time-to-clinical improvement; defined as the time from randomisation to a 2-point improvement on the world health organizations 9-point ordinal scale (ranging from 0-8; 0 being no evidence of clinical infection and 8 being death), discharge from hospital, or death (whichever occurs first)
5 secondary outcomes
To evaluate safety (number of adverse events) and tolerability (laboratory abnormalities) of IMU 838 + Oseltamivir vs. Oseltamivir alone in adult subjects with COVID-19.
Time frame: 28 days
To determine the effects of IONIC Intervention on improvement of at least two points in clinical status scale (from 0 to 8; with 8 being no evidence of clinical infection and 8 being death)
Time frame: 28 days
To assess the effects of IONIC Intervention vs. Oseltamivir on the need for invasive ventilation, renal replacement therapy or ECMO
Time frame: 14 days
To assess the effects of IONIC Intervention vs. Oseltamivir on the length of hospital and intensive care unit (ICU) stay
Time frame: 28 days
To assess the effects of IONIC Intervention vs. Oseltamivir on the time from treatment initiation to death
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2023.
- Derived from this study: PubMed 36396307Sharma K, Berry L, Vryonis E, Ali A, Lara B, Noufaily A, Parsons N, Bradley C, Haley B, Tabuso M, Arasaradnam RP. Prospective, randomised, parallel-group, open-label study to evaluate the effectiveness and safety of IMU-838, in combination with oseltamivir, in adults with COVID-19: the IONIC trial protocol. BMJ Open. 2022 Nov 17;12(11):e055205. doi: 10.1136/bmjopen-2021-055205.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IMU-838 and Oseltamivir in people with Covid 19, run by University Hospitals Coventry and Warwickshire NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate whether time-to-improvement is significantly better in IMU-838 plus Oseltamivir (IONIC Intervention) vs. Oseltamivir alone in adult subjects with COVID-19 (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04516915, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.