A Study of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, PK, & PD of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure.

Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part.

The name of the study drug involved in this study is: RLS-0071.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19; Acute Lung Injury; ALI
• Intervention / Treatment: Drug: RLS-0071 10 mg/kg; Drug: Placebo; Drug: RLS-0071 10 mg/kg; Drug: RLS-0071 40 mg/kg; Drug: RLS-0071 40 mg/kg

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 67 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed COVID-19 based on positive SARS-CoV-2 viral RNA PCR or antigen test.
• Hypoxemia.
• Radiographic evidence of opacification consistent with viral-related pneumonia.
• Weight less than 150 kg.
• Provide written informed consent.

Exclusion Criteria:

• Endotracheal intubation and mechanical ventilation.
• Noninvasive positive pressure ventilation without endotracheal intubation.
• Requires chronic oxygen therapy.
• Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents for ≥ 4 weeks duration within 3 months prior to the Screening visit.
• Use of oral corticosteroids in a dose higher than prednisone 15 mg or equivalent per day for ≥ 4 weeks duration within 3 months prior to the Screening visit.
• Systemic autoimmune disease.
• Participation in any clinical research study evaluating an investigational product or therapy within 3 months prior to the Screening visit,
• Presence of any of the following abnormal laboratory values at Screening: absolute neutrophil count < 2,000/mm3, aspartate aminotransferase or alanine aminotransferase > 5 × upper limit of normal (ULN), platelets < 50,000/mm3.
• D-dimer > 2 × ULN at Screening, as evidence of potential disseminated intravascular coagulation (DIC).
• Has confounding medical conditions, including poorly controlled diabetes, uncontrolled New York Heart Association Class III congestive heart failure, clinically significant arrhythmias not controlled by medication, idiopathic pulmonary fibrosis, interstitial lung disease, or chronic obstructive pulmonary disease.
• Has bacterial sepsis currently or suspicion thereof.
• Has cancer currently and is receiving active treatment (including radiation therapy or chemotherapy) or malignancy within the last 5 years, with the exception of curable cancer (eg, basal or squamous cell skin cancer, cervical cancer in situ, nonmedullary thyroid carcinoma) that has been adequately treated (eg, excision).
• Prior history of myocardial infarction or angina, stroke or transient ischemic attack (TIA), pulmonary embolism or deep vein thrombosis.
• Is moribund and not expected to survive 48 hours following Screening or for whom no further aggressive treatment such as mechanical ventilation is planned.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: RLS-0071 10 mg/kg; Single dose IV infusion of 10 mg/kg RLS-0071; Drug: Placebo; The placebo control will be commercial sterile saline (0.9% Sodium Chloride Injection, United States Pharmacopoeia [USP]).; Drug: RLS-0071 10 mg/kg; Multiple dose IV infusion of 10 mg/kg RLS-0071 administered every 8 hours for approximately 3 days (9 consecutive doses)
Experimental: Cohort 2	Drug: Placebo; The placebo control will be commercial sterile saline (0.9% Sodium Chloride Injection, United States Pharmacopoeia [USP]).; Drug: RLS-0071 40 mg/kg; Single dose IV infusion of 40 mg/kg RLS-0071; Drug: RLS-0071 40 mg/kg; Multiple dose IV infusion of 40 mg/kg RLS-0071 administered every 8 hours for approximately 3 days (9 consecutive doses)
Experimental: Cohort 3	Drug: RLS-0071 10 mg/kg; Single dose IV infusion of 10 mg/kg RLS-0071; Drug: Placebo; The placebo control will be commercial sterile saline (0.9% Sodium Chloride Injection, United States Pharmacopoeia [USP]).; Drug: RLS-0071 10 mg/kg; Multiple dose IV infusion of 10 mg/kg RLS-0071 administered every 8 hours for approximately 3 days (9 consecutive doses)
Experimental: Cohort 4	Drug: Placebo; The placebo control will be commercial sterile saline (0.9% Sodium Chloride Injection, United States Pharmacopoeia [USP]).; Drug: RLS-0071 40 mg/kg; Single dose IV infusion of 40 mg/kg RLS-0071; Drug: RLS-0071 40 mg/kg; Multiple dose IV infusion of 40 mg/kg RLS-0071 administered every 8 hours for approximately 3 days (9 consecutive doses)
Placebo Comparator: Placebo Cohorts 1 and 2; Placebo will be administered at the same volume and duration of IV infusion corresponding to the cohort dosing schedule.	Drug: Placebo; The placebo control will be commercial sterile saline (0.9% Sodium Chloride Injection, United States Pharmacopoeia [USP]).
Placebo Comparator: Placebo Cohorts 3 and 4; Placebo will be administered at the same volume and duration of IV infusion corresponding to the cohort dosing schedule.	Drug: Placebo; The placebo control will be commercial sterile saline (0.9% Sodium Chloride Injection, United States Pharmacopoeia [USP]).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and severity of Adverse Events, including Serious Adverse Events, by treatment group and dose level, including the frequency of premature discontinuation of study intervention due to Adverse Events.	Through study completion at Day 28 following last dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.		Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).
Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.		Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).
Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Estimates of single-dose apparent total volume of distribution for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Estimates of single-dose apparent total body clearance for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.
Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion
Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).		Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Estimates of multiple-dose apparent total volume of distribution for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.		Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).
Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.		Through study completion at Day 28 following last dose.
Overall survival.		Through Day 15 and through study completion at Day 28 following last dose.
Incidence of progression to respiratory failure requiring mechanical ventilation.		Days on ventilation while in the hospital through study completion at Day 28.
Incidence of transfer to the ICU.		Through Day 15 following last dose; through study completion at Day 28 following last dose; and duration of ICU stay days in the hospital post-dose through study completion at Day 28.
Duration of hospitalization after treatment (days).		Through study completion at Day 28 following last dose.
Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).		Through study completion at Day 28 following last dose.
Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.		Through study completion at Day 28 following last dose.
Duration of requirement for supplemental oxygen after treatment (days).		Through study completion at Day 28 following last dose.
PaO2/FiO2		Through study completion at Day 28 following last dose.
Incidence, severity, and duration after treatment (days) of new cardiovascular events as assessed by the investigator (e.g. myocardial infarction, stroke, TIA, ischemic limb) with CTCAE's latest version.		Through Day 15 and through study completion at Day 28 following last dose.
Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.		Through Day 15 and through study completion at Day 28 following last dose.
Incidence and duration after treatment (days) of dialysis.	Dialysis will be assessed by the investigator with CTCAE's latest version.	Through Day 15 and through study completion at Day 28 following last dose.
Levels of complement activity (eg, CH50).		Through study completion at Day 28 following last dose.
Levels of C1q (free and bound to RLS-0071).		Through study completion at Day 28 following last dose.

Collaborators and Investigators

• Sponsor: ReAlta Life Sciences, Inc.
• Investigators: Study Chair: Kenji Cunnion, MD, MPH, ReAlta Life Sciences, Inc.; Study Director: Linda Dell, ReAlta Life Sciences, Inc.

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): February 4, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Acute Lung Injury; ALI; Sars-CoV2; COVID-19 pneumonia; Early Respiratory Failure
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Lung Diseases; Thoracic Injuries; COVID-19; Respiratory Insufficiency; Pneumonia; Wounds and Injuries; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: RLS-0071-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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