A Study to Test BI 767551 in People With Mild to Moderate Symptoms of COVID-19

Study Overview
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Brief Summary
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This study is open to adults with mild to moderate symptoms of COVID-19 (coronavirus disease). The purpose of this study is to find out whether a medicine called BI 767551 helps people with COVID-19. BI 767551 is an antibody against the coronavirus. The study has 2 parts. Part 1 wants to find out the best dose of BI 767551 given as infusion into a vein. It also tests how BI 767551 is taken up by the body when taken via an inhaler. Participants are put into 4 groups by chance. Participants get BI 767551 or placebo once. 1 group gets a high dose of BI 767551 as an infusion into a vein 1 group gets a low dose of BI 767551 as an infusion into a vein 1 group gets BI 767551 via an inhaler 1 group gets placebo both as an infusion into a vein and via an inhaler The placebo infusion and inhaler look like the BI 767551 infusion and inhaler but do not contain any medicine. Doctors check how BI 767551 reduces the amount of coronavirus. Once the best dose of BI 767551 is found, part 2 of the study tests BI 767551 in a larger group of people. Also, in part 2, the participants get BI 767551 or placebo as an infusion into a vein once. In this part, doctors will check how many people need to be treated in a hospital or die. The results will be compared between the groups. For each part, participants are in the study for about 13 weeks. During this time, they visit the study site about 8 times and get about 3 remote visits. The doctors also regularly check participants' health and take note of any unwanted effects of BI 767551.

Official Title
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A Phase II/III Seamless, Randomized, Double-blind, Placebo-controlled, Parallel-group, Group-sequential Study to Evaluate Efficacy, Safety and Tolerability of BI 767551 for the Treatment of Symptomatic, Non-hospitalized Adults With Mild to Moderate COVID-19.

Conditions
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COVID-19

Intervention / Treatment
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* Drug: BI 767551 intravenous
* Drug: BI 767551 inhaled
* Drug: Placebo intravenous
* Drug: Placebo inhaled


Participation Criteria
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Eligibility Criteria
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Inclusion criteria phase II and III: ≥ 18 years old, males and females Signed and dated written informed consent in accordance with International Council on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial Documentation of laboratory-confirmed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a molecular test (antigen or nucleic acid) from any respiratory tract specimen (nasopharyngeal (NP) or nasal swab or saliva) collected no more than 72 hours prior to start of treatment Patients experienced mild to moderate Coronavirus Disease 2019 (COVID-19)-related symptoms or measured fever for no more than 5 days prior to start of treatment where symptoms are defined by fever, feeling feverish, fatigue, cough, shortness of breath at rest or during activity, sore throat, body pain or muscle pain/ aches, chills, headache, nasal obstruction or congestion, loss of smell or taste, nausea, diarrhea, vomiting, or dysgeusia One or more of the following signs/symptoms present on day of start of treatment: fever, feeling feverish, fatigue, cough, shortness of breath at rest or during activity, sore throat, body pain or muscle pain/ aches, chills, headache, nasal obstruction or congestion, loss of smell or taste, nausea, diarrhea, vomiting, or dysgeusia Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly Exclusion criteria phase II and III: Body weight of less than 40 kg Severe or critical COVID-19 including at least one of Oxygen saturation (SpO2) ≤ 93 % on room air or on their usual level of oxygen supplementation in case of chronic oxygen use Ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) < 300 (in case arterial blood sample was taken) History of hospitalization for COVID-19 Current or imminent need for hospitalization or immediate medical attention in the clinical opinion of the site investigator. Does not include patients hospitalized for isolation only Receipt of intravenous immunoglobulin within 12 weeks prior to Visit 2 Receipt of COVID-19 convalescent plasma treatment at any time prior to Visit 2 Receipt of any SARS-CoV-2 monoclonal antibody treatment at any time prior to Visit 2 Receipt of SARS-CoV-2 vaccine at any time prior to Visit 2 Receipt of an investigational product for COVID-19 within 5 half-lives prior to Visit 2 Receipt of systemic steroids (e.g. prednisone, dexamethasone) within 4 weeks prior to Visit 2 unless used for chronic condition Further exclusion criteria apply. Exclusion criterion phase III only: - Previous enrolment in this trial. Patients participating in Phase II are not eligible for Phase III. Re-screening is allowed once, for repeat of Quantitative Reverse Transcription Polymerase chain reaction (RT-qPCR) or antigen SARS-CoV-2 test, if required. The test method used for initial screening (RT-qPCR or antigen) should be used for re-screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This trial consists of two phases: Exploratory Phase II: Randomised, double-blind, placebo controlled, doubledummy,Phase II, parallel group design comparing different doses and modes of administration of BI 767551 to placebo. Confirmatory Phase III: Randomised, double-blind, placebo-controlled, parallel group, Phase III comparing BI 767551 to placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Phase II, Arm 1: Placebo intravenous (i.v.) + placebo inhaled<br>Single dose of sterile normal saline (NaCl 0.9%) used as placebo for intravenous (i.v.) was administered as intravenous infusion over a period of 60 minutes plus a single inhaled of solvent for dilution of BI 767551 used as placebo for inhalation administered via inhalation through a mouthpiece (Aerogen® Ultra) using a mesh nebulizer (Aerogen® Solo) on Day 1, followed by a 90-day follow-up period. The inhalation procedure was to start approximately 25 min after the start of infusion. | Drug: Placebo intravenous<br>* Placebo intravenous<br>Drug: Placebo inhaled<br>* Placebo inhaled<br>|
| Experimental: Phase II, Arm 2: BI 767551 10 milligrams (mg)/kilogram (kg) intravenous (i.v.) + placebo inhaled<br> | Drug: BI 767551 intravenous<br>* BI 767551 intravenous<br>Drug: Placebo inhaled<br>* Placebo inhaled<br>|
| Experimental: Phase II, Arm 3: BI 767551 40 mg/kg intravenous (i.v.) + placebo inhaled<br> | Drug: BI 767551 intravenous<br>* BI 767551 intravenous<br>Drug: Placebo inhaled<br>* Placebo inhaled<br>|
| Experimental: Phase II, Arm 4: Placebo intravenous (i.v.) + BI 767551 250 mg inhaled<br>Single dose of sterile normal saline (NaCl 0.9%) used as placebo for intravenous (i.v.) was administered as intravenous infusion over a period of 60 minutes plus a single inhaled of 250 milligrams (mg) of BI 767551 administered via inhalation through a mouthpiece (Aerogen® Ultra) using a mesh nebulizer (Aerogen® Solo) on Day 1, followed by a 90-day follow-up period. The inhalation procedure was to start approximately 25 min after the start of infusion. | Drug: BI 767551 inhaled<br>* BI 767551 inhaled<br>Drug: Placebo intravenous<br>* Placebo intravenous<br>|
| Experimental: Phase III, Arm 1: BI 767551 (medium or high dose infusion) or low dose inhalation<br> | Drug: BI 767551 intravenous<br>* BI 767551 intravenous<br>|
| Placebo Comparator: Phase III, Arm 2: Placebo<br> | Drug: Placebo intravenous<br>* Placebo intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: Time-weighted Change From Baseline in Viral Shedding Over 8 Days in Site Collected Nasopharyngeal (NP) Swabs by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) | Time-weighted change from baseline in viral shedding over 8 days in site collected nasopharyngeal (NP) swabs by Quantitative Reverse Transcription Polymerase chain reaction (RT-qPCR), defined as a absolute change from baseline in log10 viral load, is reported. | Up to 8 days | 
| Phase II: Time-weighted Change From Baseline in Viral Shedding Over 29 Days in Site Collected Nasopharyngeal (NP) Swabs by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) | Time-weighted change from baseline in viral shedding over 29 days in site collected nasopharyngeal (NP) swabs by Quantitative Reverse Transcription Polymerase chain reaction (RT-qPCR), defined as a absolute change from baseline in log10 viral load, is reported. | Up to 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: Number of Participants With Loss of Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Ribonucleic Acid (SARS-CoV-2 RNA) by Site Collected NP Swab at Day 4, 8, 15, 22 and 29 | Number of participants with loss of detection of Severe acute respiratory syndrome coronavirus 2 ribonucleic acid (SARS-CoV-2 RNA) by site collected NP swab at Day 4, 8, 15, 22 and 29 is report. The Yes = loss of detection of SARS-CoV-2 RNA; No = SARS-CoV-2 RNA detected; Missing = not evaluable. | At Day 4, Day 8, Day 15, Day 22, and Day 29 |