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

Primary Purpose

Acute Lung Injury, ALI, COVID-19

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

RLS-0071 10 mg/kg

RLS-0071 40 mg/kg

Placebo

RLS-0071 10 mg/kg

RLS-0071 40 mg/kg

About this trial

This is an interventional treatment trial for Acute Lung Injury focused on measuring Acute Lung Injury, Sars-CoV2, COVID-19, COVID-19 pneumonia, Early Respiratory Failure, ALI

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Henry Ford Health Systems

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Cohort 1

Cohort 2

Placebo Cohorts 1 and 2

Cohort 3

Cohort 4

Placebo Cohorts 3 and 4

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.

Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.

Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.

Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.

Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.

Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

Estimates of single-dose apparent total volume of distribution for RLS-0071.

Estimates of single-dose apparent total body clearance for RLS-0071.

Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.

Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.

Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.

Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.

Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).

Estimates of multiple-dose apparent total volume of distribution for RLS-0071.

Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.

Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.

Overall survival.

Incidence of progression to respiratory failure requiring mechanical ventilation.

Incidence of transfer to the ICU.

Duration of hospitalization after treatment (days).

Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).

Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.

Duration of requirement for supplemental oxygen after treatment (days).

PaO2/FiO2

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.

Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.

Incidence and duration after treatment (days) of dialysis.

Dialysis will be assessed by the investigator with CTCAE's latest version.

Levels of complement activity (eg, CH50).

Levels of C1q (free and bound to RLS-0071).

Full Information

NCT ID

NCT04574869

First Posted

September 16, 2020

Last Updated

January 20, 2022

Sponsor

ReAlta Life Sciences, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04574869

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Low probability of enrolling patients prior to expiry of study drug.

Study Start Date

January 2021 (Anticipated)

Primary Completion Date

September 2022 (Anticipated)

Study Completion Date

December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ReAlta Life Sciences, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lung Injury, ALI, COVID-19

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

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)

Masking

ParticipantInvestigator

Masking Description

This study is a double-blinded and randomized study. Pharmacy staff will mask infusion bags and lines to maintain the study blind.

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Title

Cohort 2

Arm Type

Experimental

Arm Title

Placebo Cohorts 1 and 2

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Cohort 3

Arm Type

Experimental

Arm Title

Cohort 4

Arm Type

Experimental

Arm Title

Placebo Cohorts 3 and 4

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

RLS-0071 10 mg/kg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

RLS-0071 40 mg/kg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

RLS-0071 10 mg/kg

Intervention Description

Multiple dose IV infusion of 10 mg/kg RLS-0071 administered every 8 hours for approximately 3 days (9 consecutive doses)

Intervention Type

Drug

Intervention Name(s)

RLS-0071 40 mg/kg

Intervention Description

Multiple dose IV infusion of 40 mg/kg RLS-0071 administered every 8 hours for approximately 3 days (9 consecutive doses)

Primary Outcome Measure Information:

Title

Time Frame

Through study completion at Day 28 following last dose.

Secondary Outcome Measure Information:

Title

Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.

Time Frame

Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

Title

Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.

Time Frame

Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

Title

Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.

Time Frame

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.

Title

Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.

Time Frame

Title

Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.

Time Frame

Title

Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

Time Frame

Title

Estimates of single-dose apparent total volume of distribution for RLS-0071.

Time Frame

Title

Estimates of single-dose apparent total body clearance for RLS-0071.

Time Frame

Title

Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.

Time Frame

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

Title

Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.

Time Frame

Title

Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.

Time Frame

Title

Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

Time Frame

Title

Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.

Time Frame

Title

Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).

Time Frame

Title

Estimates of multiple-dose apparent total volume of distribution for RLS-0071.

Time Frame

Title

Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.

Time Frame

Title

Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.

Time Frame

Through study completion at Day 28 following last dose.

Title

Overall survival.

Time Frame

Through Day 15 and through study completion at Day 28 following last dose.

Title

Incidence of progression to respiratory failure requiring mechanical ventilation.

Time Frame

Days on ventilation while in the hospital through study completion at Day 28.

Title

Incidence of transfer to the ICU.

Time Frame

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.

Title

Duration of hospitalization after treatment (days).

Time Frame

Through study completion at Day 28 following last dose.

Title

Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).

Time Frame

Through study completion at Day 28 following last dose.

Title

Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.

Time Frame

Through study completion at Day 28 following last dose.

Title

Duration of requirement for supplemental oxygen after treatment (days).

Time Frame

Through study completion at Day 28 following last dose.

Title

PaO2/FiO2

Time Frame

Through study completion at Day 28 following last dose.

Title

Time Frame

Through Day 15 and through study completion at Day 28 following last dose.

Title

Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.

Time Frame

Through Day 15 and through study completion at Day 28 following last dose.

Title

Incidence and duration after treatment (days) of dialysis.

Description

Dialysis will be assessed by the investigator with CTCAE's latest version.

Time Frame

Through Day 15 and through study completion at Day 28 following last dose.

Title

Levels of complement activity (eg, CH50).

Time Frame

Through study completion at Day 28 following last dose.

Title

Levels of C1q (free and bound to RLS-0071).

Time Frame

Through study completion at Day 28 following last dose.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

69 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kenji Cunnion, MD, MPH

Organizational Affiliation

ReAlta Life Sciences, Inc.

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Linda Dell

Organizational Affiliation

ReAlta Life Sciences, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Henry Ford Health Systems

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34473343

Citation

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.

Results Reference

derived

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

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