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

NCT04574869 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: RLS-0071-102
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Lung Injury; ALI; COVID-19

Keywords

Acute Lung Injury; Sars-CoV2; COVID-19; COVID-19 pneumonia; Early Respiratory Failure; ALI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (30)

• 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.

Study Arms (6)

Cohort 1

EXPERIMENTAL

Drug: RLS-0071 10 mg/kg; Drug: Placebo

Cohort 2

EXPERIMENTAL

Drug: RLS-0071 40 mg/kg; Drug: Placebo

Placebo Cohorts 1 and 2

PLACEBO COMPARATOR

Placebo will be administered at the same volume and duration of IV infusion corresponding to the cohort dosing schedule.

Drug: Placebo

Cohort 3

EXPERIMENTAL

Drug: Placebo; Drug: RLS-0071 10 mg/kg

Cohort 4

EXPERIMENTAL

Drug: Placebo; Drug: RLS-0071 40 mg/kg

Placebo Cohorts 3 and 4

PLACEBO COMPARATOR

Placebo will be administered at the same volume and duration of IV infusion corresponding to the cohort dosing schedule.

Drug: Placebo

Interventions

RLS-0071 10 mg/kg DRUG

Single dose IV infusion of 10 mg/kg RLS-0071

Cohort 1

RLS-0071 40 mg/kg DRUG

Single dose IV infusion of 40 mg/kg RLS-0071

Cohort 2

Placebo DRUG

The placebo control will be commercial sterile saline (0.9% Sodium Chloride Injection, United States Pharmacopoeia \[USP\]).

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Placebo Cohorts 1 and 2; Placebo Cohorts 3 and 4

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ReAlta Life Sciences, Inc.: lead

Study Sites (1)

Henry Ford Health Systems

Detroit, Michigan, 48202, United States

Location

Related Publications (1)

• 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.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

Acute Lung Injury; COVID-19; Respiratory Insufficiency

Interventions

RLS-0071

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Respiration Disorders

Study Officials

• Kenji Cunnion, MD, MPH

  ReAlta Life Sciences, Inc.

  STUDY CHAIR

• Linda Dell

  ReAlta Life Sciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study is a double-blinded and randomized study. Pharmacy staff will mask infusion bags and lines to maintain the study blind.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study intervention, RLS-0071 or placebo, will be administered as an IV infusion over 30 minutes (± 10 minutes). The following dose groups are planned: Part A (Single-Ascending Dose): * Cohort 1: low dose (single infusion) vs. placebo * Cohort 2: high dose (single infusion) vs. placebo Part B (Multiple-Ascending Dose): * Cohort 3: low dose administered q8 hours (± 1 hour) vs. placebo for 3 days (9 doses) * Cohort 4: high dose administered q8 hours (± 1 hour) vs. placebo for 3 days (9 doses)

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: October 5, 2020
• Study Start: January 1, 2021
• Primary Completion: September 1, 2022
• Study Completion: December 1, 2022
• Last Updated: February 4, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)