E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult hospitalized patients suffering from COVID-19. |
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E.1.1.1 | Medical condition in easily understood language |
Patients suffering from the disease COVID-19. |
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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 | 10084268 |
E.1.2 | Term | COVID-19 |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
• To demonstrate the efficacy of ATR-002 versus placebo in addition to standard of care based on the clinical severity status in adult hospitalized patients with COVID-19 |
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E.2.2 | Secondary objectives of the trial |
• To show that ATR-002 in addition to standard of care shortens the time to clinically relevant improvement of COVID-19 for a hierarchically ordered sequence of time-to-event endpoints • To show that the primary endpoint extended as AUC has a more favorable level under ATR-002 compared to placebo in addition to standard of care over the initial trial period of 30 days in adult hospitalized patients with COVID-19 • To explore whether survival time will be prolonged under ATR-002 compared to placebo in addition to standard of care during the initial 30 days of the trial period in adult hospitalized patients with COVID-19 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Capable of giving signed informed consent as described in Section 10.1.3 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Study participant must be at least 18 years of age at the time of signing the ICF. 3. Study participants with a laboratory confirmed diagnosis of SARS-CoV-2 infection presenting as moderate -to-severe COVID-19 requiring hospitalization for COVID-19 (Clinical Severity Status [3] or [4]) and for medical reasons (see Section 8 of the protocol). Patients presenting to the hospital without a laboratory confirmed SARS-CoV-2 infection will be tested locally for SARS-CoV-2 during the screening period. For sites in the EU: A CE certified SARS-CoV-2 PCR test kit is required to confirm infection. For sites outside the EU: SARS-CoV-2 PCR test kits certified according to local regulations are required to confirm infection. 4. Body weight at least 50 kg and have a body mass index (BMI) ≥ 18.0 kg/m2 and < 40.0 kg/m2. 5. Male or female. 6. A female study participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: a. She is not a WOCBP as defined in Section 10.3.1 of the protocol. b. Is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.3.2 of the protocol during the IMP period and for at least 4 weeks after the last dose of IMP. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of IMP. 7. A WOCBP must have a negative urine pregnancy test within 24 hours before the first dose of IMP, see Section 8.3.5 of the protocol. a. If a urine pregnancy test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required locally. In such cases, the participant must not be randomized if the serum pregnancy result is positive. b. If a serum pregnancy test is required as per local regulations, a serum pregnancy test is required locally. In such cases, the participant must not be randomized if the serum pregnancy result is positive. c. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetectable pregnancy. 8. A male study participant is eligible to participate if: a. He is azoospermic b. The partner is not a WOCBP as defined in Section 1.1.1 of the protocol. c. The partner is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.3.2 of the protocol during the IMP period and for at least 90 days after the last dose of IMP. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of IMP. d. He acknowledges that sperm donation is prohibited from the first dose of IMP until at least 90 days after the last dose of IMP. |
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E.4 | Principal exclusion criteria |
1. Patient’s clinical condition is worsening rapidly. 2. Requiring ICU admission or ventilator support at screening or at randomization. 3. Suspected bacterial, fungal, viral, or other infection (besides COVID-19). 4. History of any of the following: malignant disease, autoimmune disease, or severe liver, kidney, blood, cardiac, pulmonary, neurological, or endocrine disease as judged by the investigator. The medical monitor should be contacted by the investigator. 5. History of hypertension should have hypertension adequately controlled (BP < 140/90 mmHg) with appropriate anti-hypertensive treatment. 6. Clinically significant cardiac conduction abnormalities, including QTc prolongation of > 450 milliseconds. 7. Family history of Long QT Syndrome. 8. Heart failure class 3, or 4, as defined by the New York Heart Association (NYHA). 9. History of acute coronary syndrome (including myocardial infarction), coronary angioplasty, or stenting within 24 weeks prior to screening. 10. Patients with implanted defibrillators or permanent pacemakers. 11. Poorly controlled diabetes mellitus with an HbA1c > 7.5 %. 12. Renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome, or renal tubular acidosis. 13. Renal failure requiring renal replacement therapy or moderate renal impairment as defined by having an estimated glomerular filtration rate (eGFR, CKD-EPI) < 45 ml/min/1.73m2. 14. Chronic Obstructive Pulmonary Disease (COPD) GOLD C, or D, or hospitalization for exacerbation of COPD within 24 weeks prior to screening. 15. Other chronic lung diseases including cystic fibrosis, neuromuscular diseases, severe chest wall deformities, interstitial lung diseases, outpatient chronic non-invasive ventilation due to chronic respiratory failure. 16. Asthma with a symptom control level of "uncontrolled", according to current GINA guidelines. 17. Currently suffering from diseases that seriously affect the immune system, such as: human immunodeficiency virus (HIV) infection, or the blood system, or splenectomy, or organ/ stem cell transplantation. 18. Known Hepatitis B or C infection. 19. Any medical condition, physical examination finding or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient. 20. Alanine transaminase (ALT) or aspartate transaminase (AST) >3.0 x ULN. 21. Total bilirubin >1.0 x ULN (≥1.5 x ULN total bilirubin if known Gilbert’s syndrome). 22. Taking concomitant medication metabolized by CYP2C8 and/ or CYP2C9 and listed as “prohibited” in Section 10.5 of the protocol. 23. Taking concomitant medication of any experimental treatment or use of marketed medications including off-label use, that are intended as specific treatment for COVID-19. Any such treatments must be washed out for 30 days or at least 5 half-lives prior to randomization, whichever is longer, unless a formal written standard of care policy document requires otherwise. Inclusion needs to be approved by the investigator and medical monitor. 24. Taking medication that may seriously affect the immune system, e.g. chemotherapy, unless considered and documented as standard of care (e.g. corticosteroids) to treat COVID-19. 25. Currently participating in other clinical trials or previous treatment with an investigational medicinal product within 5 half-lives or 30 days (whichever is longer) prior to randomization. 26. Known allergy or hypersensitivity to the IMP (including excipients). 27. Study participant is pregnant or breastfeeding. 28. Patient has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities. 29. Patient is an employee of the sponsor, or an employee of any third-party organization involved into the clinical trial, or an employee of the clinical trial site, or is dependent on the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Population: All study participants fulfilling the inclusion and exclusion criteria • Target variable: Clinical severity status on a 7-point ordinal scale at Day 15 • Estimator: Odds ratio of ATR-002 in addition to standard of care versus placebo in addition to standard of care with 95% confidence interval
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Fulfillment of In-/exclusion criteria on day 1 • Target variable on day 15 |
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E.5.2 | Secondary end point(s) |
• Population defined as above • Target variables: - Time from randomization to discharge from hospital - Time to discharge from hospital or to score of ≤2 maintained for 24 hours in NEWS2, whichever occurs first - Time to resolution of fever, defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic) for at least 24 hours without antipyretics for 24 hours - Time to SpO2 >94% on room air maintained for 24 hours - Clinical severity status over the hospital period calculated as AUC from the 7-point ordinal scale at Days 3, 5, 8, 11, 15 and 30 - Survival time up to Day 30 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Population on day 1 • Target variables: - At any timepoint up to day 30 - Clinical severity status on days 3, 5, 8, 11, 15 and 30 - Survival time up to day 30 |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Georgia |
India |
Mexico |
South Africa |
Turkey |
Belgium |
Poland |
Netherlands |
Romania |
Spain |
Germany |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 16 |