E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070255 |
E.1.2 | Term | Coronavirus test positive |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Is using Adalimumab up to 2 times in the first 14 days from randomisation compared to standard care, effective in preventing and/or reducing the severity of COVID-19 disease at 28 days post randomisation? |
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E.2.2 | Secondary objectives of the trial |
What is the safety profile of using Adalimumab in those with COVID-19 disease?
What impact(if any) does Adalimumab have on the clinical course of a COVID-19 infection?
There are some further exploratory variables being researched in this trial - they are: Exploratory investigation of biomarkers from those in the trial Exploratory investigation of drug levels in the blood for those given Adalimumab Compare the benefit/risk of the two dosing regimens of Adalimumab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible for the trial if all of the following are true: • Aged at ≥ 18 years • Confirmed SARS-CoV-2 infection based on a validated test • CRP >50 mg/L or Lymphopaenia (<1.5 x 109/L) or Neutrophilia (>7.5 x 109/L) • Oxygen saturation >93% on air (pulse oximeter)
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E.4 | Principal exclusion criteria |
The participant may not enter the trial if ANY of the following apply: • Subject is considered to be in their last few weeks of life prior to this acute illness • Clinical frailty score of 8 or 9 prior to this acute illness o Note that acute delirium is not an exclusion • History of haematopoietic stem cell transplant or solid organ transplant • Chronic Obstructive Pulmonary Disease on long term oxygen therapy o Subjects with FEV1 known to be <50% will also be excluded • Concomitant use of DMARDs (including csDMARDs, tsDMARDs and bDMARDs) or other immuno-suppressants • Previous malignancy and lymphoproliferative disorders (within the last 5 years) with the exception of stable prostate cancer and basal cell carcinoma • Current participation in another therapeutic interventional clinical study for COVID-19 • De-myelinating disease • Known to be co-infected with Hepatitis B Virus, HIV • Severe hepatic impairment • Acute Kidney Injury Stage 3 (NHS England Acute Kidney Injury algorithm) • Patients with tuberculosis or other severe infections such as (non-COVID-19) sepsis, abscesses, fungal superinfection and opportunistic infections requiring treatment. • Moderate or severe heart failure (NYHA class III/IV) • Treatment with anti-TNF drug in past 180 days (9 half lives of the drug) • Pregnancy • Lactating females • Women of child bearing potential who are unwilling to use effective contraception (i.e. barrier, oral contraceptive pill, implanted contraception, or previous hysterectomy, bilateral oophorectomy) for the study and 5 months afterwards.
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E.5 End points |
E.5.1 | Primary end point(s) |
To establish whether treatment with Adalimumab is associated with a lower rate of progression to severe disease as defined by severe illness, or critical illness, or death from any cause in community care patients with COVID-19, 28 days after randomisation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
28 days after randomisation |
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E.5.2 | Secondary end point(s) |
Safety of Adalimumab
Assessment of the impact of treatment with Adalimumab on the clinical course of COVID-19 infection
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 120 days post randomisation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of trial is the point at which all samples have been analysed and all the data has been entered into the clinical database and queries resolved. The maximum recruitment target is 750 subjects ((375 per arm) and standard of care) but the study may be stopped for futility or safety on the basis of recommendation from the DSMC. The TSC may terminate the study in the event that the incidence of cases of COVID-19 drops to a point where recruitment becomes impractical. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |