E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Covid-19 with acute respiratory insufficiency |
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E.1.1.1 | Medical condition in easily understood language |
Covid-19 with acute respiratory problems |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084401 |
E.1.2 | Term | COVID-19 respiratory infection |
E.1.2 | System Organ Class | 100000004862 |
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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 evaluate the efficacy of orally administered PB432 capsules compared to placebo in hospitalised patients for 14 days in adults with stable COVID-19 with acute respiratory insufficiency |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of PB432 compared to placebo applied in patients with COVID-19 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male / female / diverse adult ≥18 years of age at time of enrolment 2. Laboratory-confirmed SARS-CoV-2 infection (COVID-19) as determined by PCR or antigen test in any defined specimen prior to enrolment; samples of first positive test collected within 8 (for symptomatic patients at the time of test) respectively 14 (for asymptomatic patients at the time of test) calendar days prior to randomisation are accepted. 3. Inpatient admitted to an isolation ward with dyspnoea and / or tachypnoea (e.g. respiratory rate >20/minute) in stable conditions (i.e. without immediate plans for intermediate (IMC) or intensive care unit (ICU) transfer) and a need for supplemental oxygen with low-flow (i.e. up to 5 l/min) nasal cannula according to investigators assessment. 4. Signed informed consent and data protection declaration prior to initiation of any trial procedures
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E.4 | Principal exclusion criteria |
1. Acute respiratory distress syndrome (ARDS) at time of inclusion2. 2. Relevant laboratory abnormality (serum liver enzymes (ASAT, ALAT, GGT) >3x upper range of normality) 3. Known hypersensitivity to trial medication or excipients 4. Presence of inflammatory gastrointestinal disease (e.g. Crohn´s Disease, or colitis ulcerosa, diverticulitis or non-infectious acute gastritis) at time of inclusion 5. Presence of acute or recurrent inflammatory disease of the gall bladder and / or biliary ducts at time of inclusion 6. Severe hepatic disease (e.g. liver cirrhosis Child Pugh B or C, ongoing viral hepatitis) at time of inclusion 7. Hereditary fructose intolerance 8. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30 ml/min) 9. Only for female patients of childbearing potential: Pregnancy, positive urine pregnancy test on Day 1, breast feeding or no use of effective contraception 10. Active malignancy (active = running or immediately planned treatment options like e.g. surgery, chemo- or radiation therapy) or condition after carcinoma not longer than 2 years without relapse, which would make it in the opinion of the investigator unsafe or unsuitable for the patient to participate in this clinical trial 11. Use of systemic immunosuppressants (except corticosteroids) within 4 weeks before inclusion into the clinical trial 12. Only for female subjects of childbearing potential: Woman who is pregnant or breast feeding, or without effective contraception 13. Patient in another clinical trial with an investigational medicianl product within 30 days before inclusion into the clinical trial 14. Known to be or suspected of being unable to comply with the clinical trial protocol (e.g. no permanent address, history of drug abuse, known to be non-compliant or presenting an unstable psychiatric history) 15. Legal incapacity and / or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the clinical trial 16. Patient in custody by juridical or official order evidence of an uncooperative attitude 17. Patient, who is a member of the staff of the study centre, staff of the sponsor or CRO, the investigator him- / herself or close relatives of the investigator Note for exclusion criterion no. 10: Watchful waiting of prostate carcinoma is not considered as an active carcinoma provided that the patient is free of symptoms and without therapy regarding the prostate carcinoma. Such a constellation does not fulfil exclusion criterion no. 10. Final decision is at the discretion of the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The daily scores of OSS (Ordinal Status Score, i.e. Patient’s Clinical Status) will be summed-up from Day 2 to Day 15, defined as SOSS-14 and Day 1 value will be used as baseline. 2. The number of days from Day 1 (randomisation) until first increase (improvement) by at least two points in OSS compared to Day 1.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The Daily Scores of OSS will be summed-up from Day 2 to Day 29, defined as SOSS-28. Time to patient satisfies categories 5, 6 or 7 on the above mentioned 7 category ordinal scale. Time to discharge from hospital (duration of hospitalisation) Time to OSS score ≤2 (ICU admission / death) Mortality Percent of patient discharged from hospital till Day 8, 15, 22, 29 Proportion of patients SARS-CoV-2 free pharyngeal swabs / sputum samples (virus-free) on Days 8, 15, 22, 29 Proportion of patients with interference of daily activities by dyspnoea at least once after discharge
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
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 | 10 |
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 | No |
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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In the protocol is defined, that availability of first draft report is the end of the clinical 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 | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |