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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Nektar Therapeutics
- Enrollment
- 30
- Locations
- 4
- Primary Endpoint
- AUC of Bempegaldesleukin [Pharmacokinetic Parameter].
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-
- •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/m
- •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.
Arms & Interventions
Bempegaldesleukin IV + Standard of Care
Intervention: Bempegaldesleukin (Drug)
Bempegaldesleukin IV + Standard of Care
Intervention: Standard of Care (Drug)
Placebo + Standard of Care
Intervention: Standard of Care (Drug)
Placebo + Standard of Care
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
AUC of Bempegaldesleukin [Pharmacokinetic Parameter].
Time Frame: Day 1: Predose, 0.5, 24, 48, 72, 120, and 168 hours post dose.
Area under the serum concentration-time curve (AUC) of bempegaldesleukin calculated from time 0 to 168 hours.
Tmax of Bempegaldesleukin [Pharmacokinetic Parameter].
Time Frame: Day 1: Predose, 0.5, 24, 48, 72, 120, and 168 hours post dose.
Time to maximum concentration of bempegaldesleukin. Cmax = maximum concentration. Tmax = time to maximum concentration.
Cmax of Bempegaldesleukin [Pharmacokinetic Parameter].
Time Frame: Day 1: Predose, 0.5, 24, 48, 72, 120, and 168 hours post dose.
Maximum observed serum concentration (Cmax) of bempegaldesleukin.
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: Safety and tolerability were evaluated from baseline up to approximately 30 days.
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).
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time Frame: The DLT evaluation period was up to approximately 7 days following the bempegaldesleukin treatment.
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.
Percent Change From Baseline for Absolute Lymphocyte Count (ALC) by Dose/Arm.
Time Frame: ALC was evaluated from baseline up to 7 days (Day 8) following the study drug administration.
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.
Secondary Outcomes
- 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.)