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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid-19; Coronavirus Disease 2019
• Intervention / Treatment: Drug: Standard of Care; Drug: Bempegaldesleukin; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hialeah, Florida, United States, 33016
      • New Generation Medical Research
    • Hialeah, Florida, United States, 33012
      • A G A Clinical Trials - HyperCore - PPDS
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners - Winter Park - HyperCore -PPDS
  • Texas
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + Standard of Care	Drug: Standard of Care; Standard of Care Treatment for COVID-19 Infection; Other: Placebo; Administered as an intravenous infusion
Experimental: Bempegaldesleukin IV + Standard of Care	Drug: Standard of Care; Standard of Care Treatment for COVID-19 Infection; Drug: Bempegaldesleukin; Administered as an intravenous infusion; Other Names: NKTR-214; BEMPEG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of Bempegaldesleukin [Pharmacokinetic Parameter].	Area under the serum concentration-time curve (AUC) of bempegaldesleukin calculated from time 0 to 168 hours.	Day 1: Predose, 0.5, 24, 48, 72, 120, and 168 hours post dose.
Cmax of Bempegaldesleukin [Pharmacokinetic Parameter].	Maximum observed serum concentration (Cmax) of bempegaldesleukin.	Day 1: Predose, 0.5, 24, 48, 72, 120, and 168 hours post dose.
Tmax of Bempegaldesleukin [Pharmacokinetic Parameter].	Time to maximum concentration of bempegaldesleukin. Cmax = maximum concentration. Tmax = time to maximum concentration.	Day 1: Predose, 0.5, 24, 48, 72, 120, and 168 hours post dose.
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]	Safety and Tolerability of bempegaldesleukin (starting at dose 0.00075 mg/kg) in combination with SOC was evaluated by incidence of Treatment-Emergent Adverse Events of Any Grade, Grade 3-4, and Grade 5 (Death).	Safety and tolerability were evaluated from baseline up to approximately 30 days.
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)	Dose finding for this study was based on the assessment of DLT of bempegaldesleukin dose levels. Number and percentage of patients with any DLT were summarized by bempegaldesleukin dose level in bempegaldesleukin plus SOC treatment groups [0.00075 mg/kg, N=5; 0.0015 mg/kg, N=5; and 0.003 mg/kg, N=5] and placebo plus SOC (N=15). Adverse events related to study drug(s) that were defined as DLTs included the following: Any Grade ≥ 3 drug-related AE.; Any Grade ≥ 3 drug-related laboratory abnormality that was clinically significant per the Investigator.; Respiratory compromise or other virus-related AE attributed to worsening COVID-19, such as severe hypoxia, cyanosis, or chest pain/pressure. The event was considered a DLT if it was confirmed to be at least possibly related to study drug, met any of the above definitions, and was confirmed to have occurred in a patient treated with bempegaldesleukin.	The DLT evaluation period was up to approximately 7 days following the bempegaldesleukin treatment.
Percent Change From Baseline for Absolute Lymphocyte Count (ALC) by Dose/Arm.	To assess the effect of bempegaldesleukin on the time course and extent of changes in absolute lymphocyte counts (ALC). Data are reported by dose and arm for Day 8 compared to baseline.	ALC was evaluated from baseline up to 7 days (Day 8) following the study drug administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Require Supplemental Oxygen.	The percentage of patients requiring supplemental oxygen was evaluated as part of disease measurements to assess efficacy. No patient in the study required supplemental oxygen.	From baseline, following the administration of study drug approximately up to 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(a); 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. The data are reported for Day 8 by arm. There were no scores rated 3 and higher per this scale at any timepoint. Abbreviations: ECMO = extracorporeal membrane oxygenation; FiO2 = fraction of inspired oxygen; PaO2 = partial pressure of arterial oxygen; SpO2 = oxygen saturation (a) If hospitalized for isolation only, record status as for ambulatory patient. Source: WHO 2020.	From baseline up to 7 days (Day 8) following the study drug administration.

Collaborators and Investigators

• Sponsor: Nektar Therapeutics
• Investigators: Study Director: Study Director, Nektar Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): May 11, 2021
• Study Completion (Actual): May 18, 2021

Study Registration Dates

• First Submitted: November 14, 2020
• First Submitted That Met QC Criteria: November 24, 2020
• First Posted (Actual): November 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Severe Acute Respiratory Syndrome Coronavirus 2; Coronavirus Disease; NKTR-214; BEMPEG; Bempegaldesleukin; CD122-Biased Agonist; CD122-Biased Cytokine; CD122; IL-2 receptor agonist; Lymphopenia; Mild COVID
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: 20-214-34

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No