Safety and Pharmacokinetics of FBR-002 for the Treatment of Patients Hospitalized With COVID-19 in Need of Supplemental Oxygen and at Risk of Severe Outcome

Study Overview
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Brief Summary
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the coronavirus associated with COVID-19 (Coronavirus Disease 2019), invading the respiratory tract, and leading to symptoms from dysgeusia, anosmia, fever, headache and cough to dyspnea and severe respiratory failure and even death. In order to obtain its pathogenic activity, the SARS-CoV-2 relies on its spike protein to enter the cells of the infected patient. This infection leads to a variable severity spectrum, with the majority of forms of mild entity (upper respiratory tract infection or lower respiratory tract without respiratory failure or insufficiency of other organs) despite the presence of a considerable share of severe infections in need hospitalization in sub-intensive or intensive area (up to 6% of cases) with invasive and non-invasive respiratory support. Approximately 14% of patients have experienced severe disease and 5% have been critically ill. In the context of global pandemic, Fab'entech is currently developing polyclonal F(ab')2 equine fragments directed against the SARS-CoV-2 spike protein. Indeed, as virus entry within the cell requires this protein, Fab'entech proposes a way to block this event, neutralizing viral replication, and therefore inhibiting pathogenic activity of the virus. The objective of this two-stage randomized, placebo-controlled, double blind, phase 2a study is to characterize the safety and pharmacokinetics of FBR-002 in patients hospitalized with COVID-19 in need of supplemental oxygen and at risk of severe outcome

Official Title
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A Two-stage Randomized, Placebo-controlled, Double-blind, Phase 2a Study to Characterize the Safety and Pharmacokinetics of FBR-002 in Patients Hospitalized With COVID-19 in Need of Supplemental Oxygen and at Risk of Severe Outcome

Conditions
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COVID-19

Intervention / Treatment
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* Drug: FBR-002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: I1. Male or female ≥ 18 years greater than or equal to 70 years of age with or without any risk factor or less than 70 years of age and the presence of at least one of the following risk factors: Arterial hypertension under treatment (all stages) Obesity (body mass index [BMI] ≥30 kg/m²) or severe obesity (BMI of ≥40 kg/m²) Diabetes (all types) Heart conditions (such as heart failure, coronary artery disease, cardiomyopathies or hypertension) Stroke or cerebrovascular disease History Chronic lung diseases, including COPD (chronic obstructive pulmonary disease), asthma (moderate-to-severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension Malignancies (solid tumors or blood malignancies) that are progressive or were diagnosed less than 5 years ago Immunocompromised state (this includes patients who are suffering from primary immunodeficiencies; patients under treatment with corticosteroids either oral or parenteral; patients receiving active chemotherapy; patients on biological treatment or treatment with Janus Kinase (JAK) inhibitors) Solid organ or blood stem cell transplant Down syndrome Known human immunodeficiency virus (HIV) infection Liver disease of stage 1 and 2 based on the Child-Pugh classification (Appendix C) Hemoglobin blood disorders (Thalassemia, Sickle Cell Disease, etc) Renal disease (grade 1 and 2 according to Kidney Disease Improving Global Outcomes (KDIGO) classification) (see Appendix D) Dementia or other neurological conditions Absence of anti-SARS-CoV2 IgM or IgG at screening I2. Written informed consent provided by the patient or by a legal representative I3. Biologically confirmed SARS-CoV-2 infection ≤ 10 days before screening I4. First onset of COVID-19 symptoms ≤ 10 days, among fever and/or chills, headache, myalgias, cough, shortness of breath, fatigue, the new loss of taste or smell I5. Findings in chest-X-ray or chest computed tomography compatible with lower respiratory tract infection* * precision for imaging: typical imaging features related to COVID-19 I6. Patient admitted to hospital for COVID-19, but outside of the Intensive Care Unit I7. Patient requiring low-flow O2 supplementation ≤ 6L/min by mask or nasal prongs at screening I8. The score of 5 on the WHO 11-point Clinical Progression Scale at screening Exclusion Criteria: E1. Score ≥ 6 on the WHO 11-point Clinical Progression Scale at screening E2. Respiration rate > 30 breaths/min in adults under low-flow (⩽ 6 L/min) oxygen E3. Liver failure of stage 3 according to the Child-Pugh classification E4. Severe renal failure (≥ grade 3 according to KDIGO classification) E5. Treatment with anti-SARS-CoV-2 immunoglobulins or any blood-derived products in the last 90 days E6. Any anti-SARS-CoV-2 vaccine injection performed less than 21 days before screening E7. Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study E8. Known allergy or hypersensitivity or intolerance to study product components E9. History of anaphylaxis during a prior administration of equine serum (i.e., anti- tetanus serum or anti-ophidic serum or anti-arachnid toxin serum or anti-rabies serum) or allergic reaction due to contact or exposure to horses E10. Participation in any other Interventional study with an investigational product in the last 30 days or within 5 half-lives of receiving the investigational product E11. Patients with short life expectancy or with any severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the patient's participation in the study E12. Septic shock

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>FBR-002 at 4.3 EU/kg on D1 and D3 or FBR-002 at 5.7 EU/kg on D1 and D3 | Drug: FBR-002<br>* Administration on D1 and D3<br>|
| Placebo Comparator: Placebo Arm<br>Two administrations of placebo at D1 and D3 | Drug: Placebo<br>* Administration on D1 and D3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events of FBR-002 | The rate of treatment-emergent adverse events (serious and non-serious) of FBR-002 in the two groups of treated patients and vs. placebo over 14 days | Day 1 to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of FBR-002 | To characterize the pharmacokinetics (PK) profile of FBR-002 on SARS-CoV-2 infected patients over time from Day D1 to D14, including the mean plasmatic concentration of FBR002 of at least 2.6 μg/mL between Day 1 and Day 7 in treated groups; | Day 1 to Day 14 | 
| Biomarkers | The comparison of the relative changes of biomarkers over the time from D1 to D14 between patients treated with placebo and patients treated with each of the two dose regimens of FBR-002 | Day 1 to Day 14 | 
| Viral load | The comparison of viral load over the time from D1 to D14 between patients treated with placebo and patients treated with each of the two dose regimens of FBR-002 | From Day 1 to Day 14 | 
| Efficacy of FBR-002 | The comparison of the rate of patients progressing into WHO-CPS ≥6 by Day 8 between patients treated with placebo and patients treated with either dose of FBR-002 | Day 8 | 
| Efficacy of FBR-002 | The comparison of the rate of patients with an improvement of at least two points based on the WHO 11-point ordinal CPS i.e., hospital discharge between patients treated with placebo and patients treated with either dose of FBR-002; this is censored at 7 days after the administration of the first dose (Day 8). | Day 8 |