A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients

NCT04458298 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: OP-101-004
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 8

Brief Summary

The primary purpose of Stage-I of this study is to evaluate the safety and tolerability of OP-101 in patients with severe COVID-19 and of Stage 2 of this study is to evaluate the efficacy of OP-101 in patients with severe COVID-19. The secondary purpose of Stage 1 and Stage 2 of this study is to determine the effect of OP-101 reducing proinflammatory cytokines biomarkers in severe COVID-19 Patients. A further secondary objective of Stage 2 of this study is: To evaluate the safety and tolerability of OP-101 in patients with severe COVID-19.

Conditions

COVID-19

Keywords

SARS-COV-2; Coronavirus; Cytokine storm; Acute respiratory distress syndrome; Inflammation; IL-6; Treatment; OP-101

Outcome Measures

Primary Outcomes (2)

• Stage I: Number of Participants with Treatment Emergent Adverse Events Graded as Assessed by CTCAE Version 4.0

  Number of participants with treatment emergent adverse events will be evaluated as a measure of safety and tolerability of OP-101 by monitoring and documenting all adverse events, which include laboratory test variables.

  Up to Day 60

• Stage II: Percentage of Participants Who Were Alive (i.e., not died due to any reason) at Day 29

  Day 29

Secondary Outcomes (21)

• Stage I: Time to Improvement (2 points) in Clinical Status Assessment Using the World Health Organization 7-Point Ordinal Scale (WHO 7OS)

  Up to Day 30

• Stage I: Time to Resolution of Fever for at least 48 hours Without Antipyretics for Patients with Documented Fever (>=37.2 degree celsius [oral], or >=37.8 degree celsius [rectal], or >=38.0 degree celsius [tympanic])

  Up to Day 30

• Stage I: Time to Improvement in Oxygenation for at least 48 hours

  Up to Day 30

• Stage I: Change from Baseline in the World Health Organization (WHO)-7 Point Ordinal Scale

  Baseline up to Day 30

• Stage I: Time to Discharge from Clinic or Hospital or to National Early Warning Score 2 (NEWS2) of <=2 and maintained for 24 hours

  Up to Day 30

Study Arms (6)

Stage I: Cohort A: OP-101 2 mg/kg

EXPERIMENTAL

Participants will receive a single intravenous (IV) infusion of OP-101 2 milligram per kilogram (mg/kg) on Day 1.

Drug: OP-101

Stage I: Cohort B: OP-101 4 mg/kg

EXPERIMENTAL

Participants will receive a single IV infusion of OP-101 4 mg/kg on Day 1.

Drug: OP-101

Stage I: Cohort C: OP-101 8 mg/kg

EXPERIMENTAL

Participants will receive a single IV infusion of OP-101 8 mg/kg on Day 1.

Drug: OP-101

Stage I: Cohort D: Placebo

PLACEBO COMPARATOR

Participants will receive a single IV infusion of matching placebo on Day 1.

Drug: Placebo

Stage II: Cohort E: OP-101 8 mg/kg

EXPERIMENTAL

Participants will receive a single IV infusion of OP-101 8 mg/kg on Days 1 and 4.

Drug: OP-101

Stage II: Cohort F: Placebo

PLACEBO COMPARATOR

Participants will receive a single IV infusion of matching placebo on Days 1 and 4.

Drug: Placebo

Interventions

OP-101 DRUG

OP-101 infusion will be administered intravenously.

Stage I: Cohort A: OP-101 2 mg/kg; Stage I: Cohort B: OP-101 4 mg/kg; Stage I: Cohort C: OP-101 8 mg/kg; Stage II: Cohort E: OP-101 8 mg/kg

Placebo DRUG

Matching placebo infusion will be administered intravenously.

Stage I: Cohort D: Placebo; Stage II: Cohort F: Placebo

Eligibility Criteria

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

You may qualify if:

• Stage I:
• Body mass index (BMI) less than or equal to (\<=) 35 kilogram per meter square (kg/m\^2)
• Positive laboratory test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory infection with recent exposure to a person with laboratory-proven SARS-CoV-2
• Patient has an ordinal scale score between 5 and 7, inclusive, using the WHO 7OS
• Hypoxemia defined by saturation of peripheral oxygen (SpO2) of less than (\<) 95 percent (%) on room air or Acute respiratory distress syndrome (ARDS)
• Occurrence of at least two of the following criteria: fever greater than (\>) 38.0 degree celsius, tachycardia \>90 beats/minute, tachypnea \>20 breaths/minute, leucocytosis \>12\*109 per liter (/L) or leucopoenia \<4 \*10\^9/L
• Enrollment must occur within 72 hours from the initiation of mechanical ventilation or high-flow oxygen
• A signed informed consent form (ICF) from the patient or the patient's legally authorized representative must be available (telephone consent is acceptable)
• Female patients may not be pregnant, lactating, or breastfeeding
• Female patients of childbearing potential must have negative result for pregnancy test at screening
• Male patients must agree to use a barrier method of contraception during the study and for 90 days after the last dose
• Participants must have an estimated glomerular filtration rate of greater than or equal to (\>=) 45 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2) at screening
• Must agree not to enroll in another study of an investigational agent prior to completion of this study.
• Stage II:
• Positive laboratory test for SARS-CoV-2 or respiratory infection with recent exposure to a person with laboratory-proven SARS-CoV-2

You may not qualify if:

• Stage I:
• Not expected to survive for more than 24 hours
• Underlying clinical condition where, in the opinion of the investigator, it would be extremely unlikely that the patient would come off ventilation (eg, motor neuron disease, Duchenne muscular dystrophy, or rapidly progressive interstitial pulmonary fibrosis)
• Severe chronic obstructive pulmonary disease requiring long-term home oxygen therapy or mechanical ventilation (noninvasive ventilation or via tracheotomy) except for continuous positive airway pressure or bi-level positive airway pressure used solely for sleep-disordered breathing
• Congestive heart failure, defined as New York Heart Association Class IV
• Acute left ventricular failure or myocardial infarction
• Currently receiving extracorporeal membrane oxygenation (ECMO) therapy
• Receiving renal dialysis therapy for chronic renal failure
• Moderate to severe liver failure (Childs-Pugh Score \>12)
• Presence of any active malignancy (other than nonmelanoma skin cancer) that required treatment within the last 2 years
• Lung transplant patient
• WHO Class III or IV pulmonary hypertension
• Documented deep venous thrombosis or pulmonary embolism within past 3 months
• Major trauma in the preceding 5 days
• Concurrent treatment with immune modulatory study drugs (e.g., anti-IL6 antibodies, Janus kinase (JAK) kinase inhibitors) or other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 within 30 days or 5 half-lives, whichever is longer, prior to dosing with OP-101; except for those that have received FDA emergency-use authorization and have become standard of care (SOC). Concurrent treatment with corticosteroids is permitted if participant has documented continued hypoxemia (SpO2 of \<95% on room air) and hyper-inflammation (CRP\>=10 mg/L) at screening.

Sponsors & Collaborators

• Ashvattha Therapeutics, Inc.: lead

Study Sites (8)

Research Site

Loma Linda, California, 92354, United States

Location

Research site

Fort Lauderdale, Florida, 33316, United States

Location

Research site

Jacksonville, Florida, 32209, United States

Location

Research Site

Atlanta, Georgia, 30342, United States

Location

Research site

Baltimore, Maryland, 21287, United States

Location

Research Site

Sioux Falls, South Dakota, 57105, United States

Location

Research Site

Amarillo, Texas, 79109, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Cytokine Release Syndrome; Respiratory Distress Syndrome; Inflammation

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Respiration Disorders

Study Design

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

Study Record Dates

• First Submitted: June 29, 2020
• First Posted: July 7, 2020
• Study Start: August 11, 2020
• Primary Completion: August 12, 2022
• Study Completion: August 12, 2022
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)