A Placebo Controlled Trial of Bempegaldesleukin (BEMPEG; NKTR-214) With Standard of Care in Patients With Mild COVID-19

Study Overview
=================
Brief Summary
-----------------
The main purpose of this phase-1b, multicenter, randomized double-blind, placebo-controlled, trial is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of bempegaldesleukin (BEMPEG; NKTR-214) in combination with standard of care (SOC) in adult patients with mild COVID-19 (coronavirus disease 2019). The trial will also define the recommended phase 2 dose (RP2D) of bempegaldesleukin in patients with mild COVID-19.

Official Title
-----------------
A Phase 1b, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Bempegaldesleukin (BEMPEG; NKTR-214) Plus Standard of Care Versus Placebo Plus Standard of Care in Adults With Mild COVID-19

Conditions
-----------------
Covid-19, Coronavirus Disease 2019

Intervention / Treatment
-----------------
* Drug: Bempegaldesleukin
* Drug: Standard of Care
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients, age 18 years or older on the day of signing the informed consent form. Agrees to admission to an in-patient facility for monitoring from Days 1 to 8, inclusive. Symptoms of mild illness with COVID-19 without shortness of breath, dyspnea, or clinical signs indicative of more serious COVID-19. Laboratory confirmed SARS-CoV-2 infection within 4 days prior to the screening visit or during the 7-day screening period. Respiratory rate < 20 breaths per minute, heart rate < 90 beats per minute (bpm). Oxygen saturation by pulse oximetry > 93% on room air. Body mass index < 35 kg/m2. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min. Alanine transaminase (ALT) or aspartate transaminase (AST) < 2 x upper limit of normal (ULN) and total bilirubin < 1.5 x ULN. Agrees to not participate in another clinical trial for the treatment of COVID-19 while on study unless the patient's condition has worsened and is considered to be moderate, severe, or critical by the Investigator. Exclusion Criteria: Shortness of breath, hypoxia, or signs of serious lower airway disease. C-reactive protein, lactate dehydrogenase (LDH), or interleukin-6 (IL-6) > 1.5 x ULN. D-dimer or ferritin > 1.5 x ULN. Imminently requiring, or currently on, mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Systolic blood pressure < 90 mm Hg or diastolic blood pressure < 60 mm Hg. Evidence of acute respiratory distress syndrome (ARDS) or systemic inflammatory response syndrome (SIRS)/shock. Known cardiovascular history, including unstable or deteriorating cardiac disease. Autoimmune disease. History of pulmonary embolism (PE), deep vein thrombosis (DVT), or prior clinically significant venous or non-cerebrovascular accident/transient ischemic attack arterial thromboembolic event. Central nervous system disease or dysfunction. Requirement for > 2 anti-hypertensive medications. Unwilling to refrain from alcohol consumption from Day 1 of admission to the in-patient facility until discharge from the facility. Adrenal insufficiency. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bempegaldesleukin IV + Standard of Care<br> | Drug: Bempegaldesleukin<br>* Administered as an intravenous infusion<br>* Other names: BEMPEG;Drug: Standard of Care<br>* Standard of Care Treatment for COVID-19 Infection<br>|
| Placebo Comparator: Placebo + Standard of Care<br> | Drug: Standard of Care<br>* Standard of Care Treatment for COVID-19 Infection<br>Other: Placebo<br>* Administered as an intravenous infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of BEMPEG/standard of care (SOC) (PK). | Area under the serum concentration-time curve (AUC) of BEMPEG /SOC. | Approximately 30 days | 
| Cmax of BEMPEG /SOC (PK). | Maximum observed serum concentration (Cmax) of BEMPEG /SOC. | Approximately 30 days | 
| Tmax of BEMPEG /SOC (PK). | Time to Cmax (Tmax) of BEMPEG /SOC. | Approximately 30 days | 
| Incidence of adverse events. |  | Approximately 30 days | 
| Incidence of treatment emergent adverse events (TEAEs). |  | Approximately 30 days | 
| Incidence of serious adverse events (SAEs). |  | Approximately 30 days | 
| Incidence of dose limiting toxicities (DLT) for BEMPEG. |  | Approximately 30 days | 
| Presence and levels of anti-drug antibodies directed to BEMPEG. |  | Approximately 30 days | 
| Fold change from baseline in absolute lymphocyte count by Central Laboratory. |  | Approximately 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who require supplemental oxygen. |  | Approximately 30 days | 
| Change from baseline on the daily collection World Health Organization (WHO) Clinical Progression Scale, an 11-point clinical status ordinal scale. | The WHO Clinical Progression Scale scores and descriptors are as follows: 0- Uninfected; no viral RNA detected; 1- Asymptomatic; viral RNA detected; 2- Symptomatic; independent; 3- Symptomatic; assistance needed; 4- Hospitalized, no oxygen therapy; 5- Hospitalized; oxygen by mask or nasal prongs ; 6- Hospitalized; oxygen by non-invasive ventilation or high-flow; 7- Intubation and mechanical ventilation, PaO2/FiO2 ≥ 150 or SpO2/FiO2 ≥ 200; 8- Mechanical ventilation, PaO2/FiO2 < 150 (SpO2/FiO2 < 200) or vasopressors; 9- Mechanical ventilation, PaO2/FiO2 < 150 and vasopressors, dialysis, or ECMO; 10- Death Abbreviations: ECMO = extracorporeal membrane oxygenation; FiO2 = fraction of inspired oxygen; PaO2 = partial pressure of arterial oxygen; SpO2 = oxygen saturation If hospitalized for isolation only, record status as for ambulatory patient. Source: WHO 2020. | Approximately 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BEMPEG, Bempegaldesleukin, CD122, CD122-Biased Agonist, CD122-Biased Cytokine, Coronavirus Disease, COVID-19, IL-2 receptor agonist, Lymphopenia, Mild COVID, NKTR-214, SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2