Evaluation of the Safety and Efficacy of Razuprotafib in Hospitalized Subjects With Coronavirus Disease 2019

NCT04511650 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AKB-9778-CI-6001
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 7

Brief Summary

This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter, dose escalation and proof-of-concept study to evaluate the safety and efficacy of razuprotafib, administered 3 times daily (TID) (every 8 hours \[Q8H\]), in hospitalized subjects with moderate to severe Coronavirus disease 2019 (COVID-19) receiving standard of care therapy. The study was planned to include 2 parts with Part 1 comprising the dose escalation period of the study and Part 2 comprising the proof-of-concept safety and efficacy period of the study.

Conditions

COVID-19; Acute Respiratory Distress Syndrome (ARDS)

Keywords

COVID-19; ARDS; Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Outcome Measures

Primary Outcomes (1)

• Number and Percent of Subjects Who Were Alive and Free of Respiratory Failure Prior to Day 7 and Day 28

  All results were summarized descriptively by treatment arm and expressed as proportions, along with corresponding 95%CI of the difference between response rates, and p-values using Cochran-Mantel-Haenszel (CMH). The 95% CI will be constructed using the normal approximation method. Respiratory failure was defined as subjects who were on invasive mechanical ventilation; received oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20L/min with fraction of delivered oxygen ≥0.5) noninvasive positive pressure ventilation or extracorporeal membrane oxygenation; or had a clinical diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation).Subjects who died prior to the study timepoint (Day 7 or Day 28) were imputed based on the worst outcome.

  Baseline up to Day 7 and Day 28

Secondary Outcomes (14)

• Summary of The Mean Change From Baseline in D-Dimer at Day 7 and 28

  at Day 7 and 28

• Summary of Change From Baseline in C-Reactive Protein (CRP) at Day 7 and 28

  at Day 7 and 28

• Number of Participants Who Improve by at Least 2 Categories on the NIAID 8-point Ordinal Scale From Baseline to Day 7 and Baseline to Day 28

  from baseline to Day 7 and baseline to Day 28

• Number of Participants Who Were Discharged and Free of Respiratory Failure Prior to Day 7 and Day 28

  Day 7 and Day 28

• Number of Participants Alive and Not Requiring Invasive Mechanical Ventilation at Any Time

  Baseline up to Day 28

Other Outcomes (1)

• Summary of Razuprotafib Plasma Concentration

  razuprotafib plasma concentrations 30 and 90 minutes post-dose on Days 1 and 6

Study Arms (3)

Razuprotafib 10 mg

EXPERIMENTAL

Active Comparator

Drug: Razuprotafib Subcutaneous Solution

Placebo

PLACEBO COMPARATOR

Placebo Comparator

Drug: Placebo Subcutaneous Solution

Razuprotafib 20 mg

EXPERIMENTAL

Active Comparator

Drug: Razuprotafib Subcutaneous Solution

Interventions

Razuprotafib Subcutaneous Solution DRUG

Up to 3 daily dose levels of Razuprotafib Subcutaneous Solution will be evaluated. Doses will be administered subcutaneously three times daily (Q8H) for 7 days.

Also known as: Razuprotafib 10 mg and 20 mg solution

Razuprotafib 10 mg; Razuprotafib 20 mg

Placebo Subcutaneous Solution DRUG

Matched vehicle-controlled placebo solution will be administered subcutaneously three times daily (Q8H) for 7 days

Also known as: Placebo comparator

Placebo

Eligibility Criteria

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

You may qualify if:

• Ability to understand and provide informed consent;
• Males and non-pregnant females 18 years of age or older at the time of Screening;
• Laboratory-confirmed active SARS-CoV-2 infection within 72 hours prior to randomization, or (if testing results cannot be obtained) by evidence of progressive disease suggestive of ongoing SARS-CoV-2 infection;
• Females of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception through Day 28; and have a negative urine pregnancy test during Screening;
• Currently hospitalized, receiving standard of care therapy for COVID-19, and meets the criteria for moderate or severe COVID-19, as follows: Moderate = symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion and with respiratory rate at 20 or greater breaths/min, Peripheral capillary oxygen saturation (SpO2) \>93% on room air at sea level, or heart rate at 90 or greater beats/min; Severe = symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness, shortness of breath at rest, or respiratory distress, and respiratory rate at 30 or greater breaths/min, heart rate at 125 or greater beats/min, or SpO2 \>93% on room air at sea level or (partial pressure of oxygen:fraction of inspired oxygen (PaO2:FiO2) \<300.

You may not qualify if:

• Inability to initiate study drug within 12 hours after randomization;
• Female of childbearing potential who is unable or unwilling to forego breastfeeding through Day 28;
• Systolic blood pressure \<100 mmHg;
• In shock or requiring pressor support;
• Respiratory failure, defined as subjects who are on mechanical ventilation; are receiving oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen of 0.5 or greater), noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation (ECMO); or have a clinical diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation);
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 × the upper limit of normal (ULN);
• Total bilirubin \>2 × ULN;
• Estimated glomerular filtration rate \<30 mL/min or receiving hemodialysis or hemofiltration;
• Moribund subject not expected to survive 24 hours in the opinion of the treating clinical team;
• Any concurrent serious medical condition (eg, active malignancies on chemotherapy, post organ transplant, end stage congestive heart failure) or not likely to respond to treatment;
• Use of cytochrome P450 (CYP) 2 subfamily C, polypeptide 8 (2C8) substrates (eg, repaglinide, paclitaxel, or cerivastatin) or CYP3A4 substrates (eg, amlodipine, budesonide, dasabuvir, enzalutamide, imatinib, lopinavir, loperamide, saquinavir, sildenafil, midazolam, or montelukast);
• Use of CYP2C8 inhibitors (eg, gemfibrozil, fluvoxamine, or ketoconazole);
• Participation in another investigational study during the present study through the last visit (Day 28); or
• Previous randomization in this study.

Sponsors & Collaborators

• EyePoint Pharmaceuticals, Inc.: lead

Study Sites (7)

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California- Irvine Medical Center

Orange, California, 92868, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Snake River Research

Idaho Falls, Idaho, 83404, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02905, United States

Location

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome

Interventions

Solutions

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Results Point of Contact

• Title: Dario Paggiarino, MD
• Organization: EyePoint Pharmaceuticals, Inc.

dpaggiarino@eyepointpharma.com

8589670016

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study was planned to include 2 parts with Part 1 comprising the dose escalation period of the study and Part 2 comprising the proof-of-concept safety and efficacy period of the study. Although The Data Review Committee (DRC) recommended to continue with the study after the completion of Part 1, Step 1, the Sponsor elected to discontinue the study due to business-related reasons.

Study Record Dates

• First Submitted: August 7, 2020
• First Posted: August 13, 2020
• Study Start: October 21, 2020
• Primary Completion: February 26, 2021
• Study Completion: February 26, 2021
• Last Updated: June 8, 2023
• Results First Posted: June 8, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)