E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 with acute respiratory infection |
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E.1.1.1 | Medical condition in easily understood language |
COVID-19 with acute respiratory infection |
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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 |
The trial is conducted to assess the efficacy of 2 weeks of treatment with 4 x 300 mg (total 1200 mg)/day oral PB432 in acute symptomatic COVID-19 outpatients with new onset of cough. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of PB432 treatment in the studied out-patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Male / female / diverse adults between ≥18 and ≤60 years of age at enrolment 2 Acute coughing with new onset of cough, i.e., starting within 48 h (or 2 days) before enrolment and with sufficiently high coughing intensity, defined as a minimum score of 5 on 11-point NRS at Visit 1 3 Signed informed consent and data protection declaration for SARS-CoV-2 antigen test prior to initiation of this trial-related procedure 4 Confirmed SARS-CoV-2 infection (by test on-site) as determined by antigen test at Visit 1 before randomisation 5 Signed informed consent and data protection declaration prior to initiation of any further trial procedures beyond SARS-CoV-2 antigen test Note: For screening activities in first stage (confirmation of SARS-CoV-2 by antigen test) only inclusion criteria 1., 2. and 3. must be confirmed
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E.4 | Principal exclusion criteria |
1 Any clinical indication for immediate hospitalisation 2 Need for supplemental oxygen 3 Clinical indication for immediate systemic antibiotic therapy 4 Patients that at the discretion of the responsible physician are likely to benefit from COVID-19-specific antiviral therapy 5 Medical history suggesting chronic or readily recurrent sinusitis or bronchitis i.e., without previous acute sinusitis or bronchitis 6 At time of study inclusion chronic cough (> 6 weeks), anamnestic knowledge of bronchiectasis, suspected pneumonia, and mucoviscidosis unless consistently treated at a constant dose from 1 week before Visit 1 7 Exacerbation of COPD or asthma bronchiale with the need of systemic steroids 8 Acute symptoms of a known allergic rhinitis 9 Use of not permitted previous / concomitant medication or therapy and any other medication regularly used to treat concomitant or chronic diseases that is known to interfere with cough or mucus formation 10 Use of, or anticipated use of inhaled, intranasal, or systemic steroid treatment during the trial 11 Inflammatory gastrointestinal or severe hepatic disease or inflammation of the gallbladder or bile duct at the time of inclusion or within the last 6 months before Visit 1 12 Known hypersensitivity to trial medication or its excipients 13 Patients with rare hereditary problems of fructose intolerance 14 Only for patients of childbearing potential: Pregnancy, positive urine pregnancy test on Day 0, breast feeding or no use of effective contraception 15 Malignancy (active = running or immediately planned treatment options like e.g., surgery, chemo- or radiation therapy) or condition after carcinoma not longer than 5 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. Watchful waiting in case of prostate carcinoma is not considered as an active malignancy, provided that the patient is free of symptoms and without therapy regarding the prostate carcinoma. Such a constellation does not fulfil this exclusion criterion. Final decision is at the discretion of the investigator 16 Participation in clinical trial within 30 days before screening 17 Known to be or suspected of being unable to comply with the study protocol (e.g., no permanent address, history of drug abuse, known to be non-compliant or presenting an unstable psychiatric history) 18 Legal incapacity and / or other circumstances rendering the patient unable to understand the nature, scope, and possible impact of the trial 19 Patient in custody by juridical or official order evidence of an uncooperative attitude 20 Patient, who is a member of the staff of the study center, staff of the sponsor or CRO, the investigator him- / herself or close relatives of the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
The following main efficacy endpoints will be analysed using the eDiary data: 1. Number of coughing fits during the day using a manual counter from Day 1 to Day 13 2. Severity of typical COVID-19-symptoms from Day 0 to Day 13 using a NRS 11
The following main efficacy endpoints will be analysed using the investigator’s assessments: 1. Severity of typical COVID-19-symptoms from at each Visit using a NRS 11
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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 following exploratory efficacy endpoints will be analysed using the eDiary data: 1. Symptom rate and extent 2. Sleep disturbance due to any COVID-19 related symptom 3. Global judgement of efficacy (patient’s ratings, 4-Point Verbal Rating Scale) 4. Time to 50 % reduction in coughing fits compared to Day 1 5. Time to 50 % reduction in coughing fits compared to Day of maximum coughing fits 6. Time from Day 0 to symptom resolution or alleviation of cough and all typical COVID-19 symptoms 7. Time from Day of maximum symptom score to symptom resolution or alleviation of cough and all typical COVID-19 symptoms 8. Proportion of patients with no coughing fits separately for each study day 9. Proportion of patients with no symptoms (for each symptom and total core) separately for each study day assessed on a 11-scale VAS (0-10) 10. Proportion of patients with dyspnoea while climbing stairs
The following further exploratory efficacy endpoints will be analysed: 1. Proportion of patients hospitalized during study or on Visit 3 (Day 14 or discontinuation)
The following safety endpoints will be analysed: 1. Frequency and intensity of adverse events (AE)
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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 | Yes |
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 | 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 | 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 | 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 | 11 |
E.8.9.1 | In the Member State concerned days | |