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

• ClinicalTrials.gov Identifier: NCT04574869
• Recruitment Status: Not yet recruiting
• First Posted: October 5, 2020
• Last Update Posted: October 5, 2020
• Sponsor: ReAlta Life Sciences, Inc.
• Information provided by (Responsible Party): ReAlta Life Sciences, Inc.

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.

Condition or disease	Intervention/treatment	Phase
Acute Lung Injury; ALI; COVID-19	Drug: RLS-0071; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment

Intervention 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: Double (Participant, Investigator)
• Masking Description: This study is a double-blinded and randomized study. Pharmacy staff will mask infusion bags and lines to maintain the study blind.
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: October 2020
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: July 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: RLS-0071 administered as Single-Ascending Low Dose; Patients will receive a single low-dose infusion of RLS-0071 or placebo.	Drug: RLS-0071; RLS-0071 is a novel peptide that is being developed for the treatment of acute lung injury (ALI) due to coronavirus disease (COVID-19) pneumonia in early respiratory failure.; Other Name: Cohort 1 - single low dose
Experimental: RLS-0071 administered as Single-Ascending High Dose; Patients will receive a single high-dose infusion of RLS-0071 or placebo.	Drug: RLS-0071; RLS-0071 is a novel peptide that is being developed for the treatment of acute lung injury (ALI) due to coronavirus disease (COVID-19) pneumonia in early respiratory failure.; Other Name: Cohort 2 - single high dose
Placebo Comparator: Placebo administered as Single-Ascending Doses; Placebo will be administered at the same volume and duration of IV infusion corresponding to the dosing cohort schedules.	Drug: Placebo; The placebo control will be 0.9% Sodium Chloride Injection, United States Pharmacopoeia (USP).; Other Name: Cohort 1 & Cohort 2 single dose
Experimental: RLS-0071 administered as Multiple-Ascending Low Doses; Patients will receive treatment with RLS-0071 low dose or placebo approximately 3 days (i.e., q8 hours [± 1 hour] for 9 consecutive doses).	Drug: RLS-0071; RLS-0071 is a novel peptide that is being developed for the treatment of acute lung injury (ALI) due to coronavirus disease (COVID-19) pneumonia in early respiratory failure.; Other Name: Cohort 3 - multiple low doses
Experimental: RLS-0071 administered as Multiple-Ascending High Doses; Patients will receive treatment with RLS-0071 high dose or placebo approximately 3 days (i.e., q8 hours [± 1 hour] for 9 consecutive doses).	Drug: RLS-0071; RLS-0071 is a novel peptide that is being developed for the treatment of acute lung injury (ALI) due to coronavirus disease (COVID-19) pneumonia in early respiratory failure.; Other Name: Cohort 4 - multiple high doses
Placebo Comparator: Placebo administered as Multiple-Ascending Doses; Placebo will be administered approximately 3 days (i.e., q8 hours [± 1 hour] for 9 consecutive doses).	Drug: Placebo; The placebo control will be 0.9% Sodium Chloride Injection, United States Pharmacopoeia (USP).; Other Name: Cohort 3 & Cohort 4 multiple doses

Outcome Measures

Primary Outcome Measures :

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. [ Time Frame: Through study completion at Day 28 following last dose. ]

Secondary Outcome Measures :

1. 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). ]
2. 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). ]
3. 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. ]
4. Estimates of single-dose time to maximum plasma concentration (Tmax) 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. ]
5. Estimates of single-dose minimum plasma concentration (Cmin) 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. ]
6. Estimates of single-dose area under the plasma concentration-time curve (AUC) 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. ]
7. Estimates of single-dose apparent total volume of distribution 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. ]
8. Estimates of single-dose apparent total body clearance 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. ]
9. 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), 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. ]
10. Estimates of multiple-dose maximum plasma concentration (Cmax) 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). ]
11. Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) 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). ]
12. Estimates of multiple-dose area under the plasma concentration-time curve (AUC) 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). ]
13. Estimates of multiple-dose average plasma drug concentration observed (Cavg) 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). ]
14. Estimates of multiple-dose trough concentration prior to dose administration (Ctrough). [ 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). ]
15. Estimates of multiple-dose apparent total volume of distribution 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). ]
16. Estimates of multiple-dose apparent total body clearance 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). ]
17. Estimates of multiple-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). ]
18. 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. ]
19. Overall survival. [ Time Frame: Through Day 15 and through study completion at Day 28 following last dose. ]
20. Incidence of progression to respiratory failure requiring mechanical ventilation. [ Time Frame: Days on ventilation while in the hospital through study completion at Day 28. ]
21. 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. ]
22. Duration of hospitalization after treatment (days). [ Time Frame: Through study completion at Day 28 following last dose. ]
23. Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C). [ Time Frame: Through study completion at Day 28 following last dose. ]
24. 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. ]
25. Duration of requirement for supplemental oxygen after treatment (days). [ Time Frame: Through study completion at Day 28 following last dose. ]
26. PaO2/FiO2 [ Time Frame: Through study completion at Day 28 following last dose. ]
27. 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. [ Time Frame: Through Day 15 and through study completion at Day 28 following last dose. ]
28. 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. ]
29. Incidence and duration after treatment (days) of dialysis. [ Time Frame: Through Day 15 and through study completion at Day 28 following last dose. ]
    Dialysis will be assessed by the investigator with CTCAE's latest version.
30. Levels of complement activity (eg, CH50). [ Time Frame: Through study completion at Day 28 following last dose. ]
31. Levels of C1q (free and bound to RLS-0071). [ Time Frame: Through study completion at Day 28 following last dose. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 69 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Linda Dell; 757-901-0330; ldell@realtals.com

Contact: Rocio Navarro; 301-762-6100 ext 162; rnavarro@rrdintl.com

Locations

United States, Florida

Prestige Clinical Research Center

Coral Gables, Florida, United States, 33134

Contact: Naty Diaz 305-907-6960 naty@pcresearchcenter.com

Principal Investigator: Efrain Garcia, MD

Sponsors and Collaborators

ReAlta Life Sciences, Inc.

Investigators

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

More Information

• Responsible Party: ReAlta Life Sciences, Inc.
• ClinicalTrials.gov Identifier: NCT04574869
• Other Study ID Numbers: RLS-0071-102
• First Posted: October 5, 2020
• Last Update Posted: October 5, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ReAlta Life Sciences, Inc.:

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

Additional relevant MeSH terms:

Pneumonia; Respiratory Insufficiency; Lung Injury; Acute Lung Injury; Respiratory Distress Syndrome, Adult; Wounds and Injuries; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Respiration Disorders; Thoracic Injuries