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

NCT04646044 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 20-214-34
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

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.

Conditions

Covid-19; Coronavirus Disease 2019

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (2)

• Percentage of Patients Who Require 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.

  From baseline up to 7 days (Day 8) following the study drug administration.

Study Arms (2)

Bempegaldesleukin IV + Standard of Care

EXPERIMENTAL

Drug: Bempegaldesleukin; Drug: Standard of Care

Placebo + Standard of Care

PLACEBO COMPARATOR

Drug: Standard of Care; Other: Placebo

Interventions

Bempegaldesleukin DRUG

Administered as an intravenous infusion

Also known as: NKTR-214, BEMPEG

Bempegaldesleukin IV + Standard of Care

Standard of Care DRUG

Standard of Care Treatment for COVID-19 Infection

Bempegaldesleukin IV + Standard of Care; Placebo + Standard of Care

Placebo OTHER

Administered as an intravenous infusion

Placebo + Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nektar Therapeutics: lead

Study Sites (4)

A G A Clinical Trials - HyperCore - PPDS

Hialeah, Florida, 33012, United States

Location

New Generation Medical Research

Hialeah, Florida, 33016, United States

Location

Clinical Site Partners - Winter Park - HyperCore -PPDS

Winter Park, Florida, 32789, United States

Location

SMS Clinical Research, LLC

Mesquite, Texas, 75149, United States

Location

MeSH Terms

Conditions

COVID-19; Lymphopenia

Interventions

bempegaldesleukin; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Nektar Therapeutics

StudyInquiry@nektar.com

855-482-8676

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2020
• First Posted: November 27, 2020
• Study Start: November 13, 2020
• Primary Completion: May 11, 2021
• Study Completion: May 18, 2021
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-03

Locations

US (4)