A Clinical Trial Evaluating the Safety and Efficacy of AP1189 Versus Placebo as an add-on to Standard of Care in Participants With Respiratory Insufficiency Expected to be Caused by Infection With Respiratory Viruses

A Randomized, Double-blind, Multicentre, Placebo-controlled, Proof-of-concept Clinical Trial Evaluating the Safety and Efficacy of the Biased Melanocortin Agonist AP1189 Versus Placebo as an add-on to Standard of Care (SOC) in Participants With RESPIRatory Insufficiency Expected to be Caused by Infection With Respiratory Viruses, Including Influenza, Respiratory Syncytial Virus, and Coronavirus

A clinical study to evaluate the efficacy and safety of once daily oral dosing of 100 mg AP1189 or placebo administered for 14 days, as an add-on to standard of care (SOC) in participants with respiratory insufficiency expected to be caused by respiratory viral infection.

The purpose of the trial is to evaluate the efficacy and safety 14 days daily treatment of oral AP1189 at a dose or 100 mg as an add-on to SOC treatment.

The aim is to have 96 participants randomized and completing the study. They will be randomized in a 1:1 ratio to one of the following two groups:

• Group A (48 participants): AP1189 tablets 100 mg, once daily for 14 days as an add-on to SOC
• Group B (48 participants): placebo tablets once daily for 14 days as an add-on to SOC.

Inclusion Criteria:

• Written informed consent has been obtained prior to initiating any study-specific procedures
• Expected respiratory viral infection, and positive for either SARS-COV-2, Influenza A or B, or RSV as confirmed by a bedside LAF test, qualitative PCR, or quantitative PCR (Q-PCR).
• Hospitalized with respiratory insufficiency expected to be caused by respiratory viral infection defined by SpO2 ≤ 93 % on ambient air or supplementary oxygen supply via nasal catheter or facial mask (WHO Clinical Progression Scale score 5 or 6). Or in participants with hypercapnic respiratory failure (usually due to COPD) the SpO2 threshold is SpO2 ≤ 85 %.
• Duration of disease from first symptom< 15 days before enrolment
• Females of childbearing potential using reliable means of contraception or are post-menopausal or are surgically sterilized
• Females of childbearing potential with a negative pregnancy test at screening and baseline
• As the morbidity and mortality of respiratory infections are many fold increased in vulnerable participants, vulnerable participants are not excluded but included as subgroups.
• Screened within 24 hours of hospital admission to the hospital, or within 24 hours of receiving a patient, if the patient is transferred from another hospital or another hospital department due to respiratory distress

Exclusion Criteria:

• In the investigator's opinion, progression to death is imminent and inevitable irrespective of the provision of treatment
• Already meeting any component of the primary composite endpoint at screening, defined as the presence of any of the following: invasive mechanical ventilation, ECMO, cardiovascular organ support (balloon pump or inotropes/vasopressors), or renal failure (Cockcroft-Gault estimated creatinine clearance <15 ml/min, haemofiltration or dialysis). Note: participants qualifying under inclusion criterion 8b (pre-existing renal insufficiency or dialysis) are excluded only if they meet any of the other criteria (invasive mechanical ventilation, ECMO, or cardiovascular organ support). Participants who are physically located in an ICU or HDU but do not meet the above physiological criteria are not excluded on that basis alone.
• Participating in other drug clinical trials
• Any condition that in the view of the screening physician would suggest that the participant is unable to comply with study protocol and procedures
• Participants who have initiated treatment within 3 months prior to screening with immunosuppressive or immunomodulatory treatments for chronic autoimmune diseases. Administration of steroids or other immunosuppressive medicines implemented as standard-of-care for the treatment of the respiratory viral infection is acceptable. Asthma/COPD participants are allowed to use their habitual inhalation spray containing adrenocortical hormone.
• Pregnant women or nursing (breastfeeding) mothers