Clinical trial NCT04458298: A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients
Official title: A Two-Stage, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of OP-101 (Dendrimer N-acetyl-cysteine) in Patients With Severe COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: SARS-COV-2
Coronavirus
Cytokine storm
Acute respiratory distress syndrome
Inflammation
IL-6
Treatment
OP-101
Lead sponsor: Ashvattha Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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
* Patient has an ordinal scale score between 5 and 8, inclusive, using the WHO 10OS.
* Patients with an ordinal score of 5 must be receiving oxygen by mask at a rate of 10 L or greater
* Hypoxemia defined by SpO2 of \<95% on room air or diagnosed with ARDS
* Hyperinflammation (elevated CRP \> upper limit of local normal for laboratory range) at screening
* A signed 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
* Patients must have an estimated glomerular filtration rate of \>= 30 mL/min/1.73 m\^2 at screening
* Male patients must agree to use a barrier method of contraception during the study and for 90 days after the last dose
* Must agree not to enroll in another study of an investigational agent prior to completion of this study.

Exclusion Criteria:

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.
* Has lost or donated \>450 mL of whole blood or blood products within 30 days before screening
* Has any finding that, in the view of the investigator or medical monitor, would compromise the patient's safety requirements
* Is employed by the Sponsor, the contract research organization, or the study site (permanent, temporary contract worker, or designee responsible for the conduct of the study), or is a family member (spouse, parent, sibling, or child) of the Sponsor, contract research organization, or study site employee.

Stage II:

* 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 (e.g., 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 ECMO therapy
* Receiving renal dialysis therapy for end stage renal disease
* 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 approved or emergency use authorized immune modulatory study drugs (eg, anti-IL6 antibodies \[tocilizumab\], JAK kinase inhibitors \[baricitinib\]) or other investigational agents with actual or possible direct acting antiviral activity against SARS-CoV-2 within 30 days or 5 half-lives, whichever is longer, before dosing with OP-101.
* Has lost or donated \>450 mL of whole blood or blood products within 30 days before screening
* Mechanical ventilation for \>72 hours at the time of dosing
* Has any finding that, in the view of the investigator or medical monitor, would compromise the patient's safety requirements
* Is employed by the Sponsor, the contract research organization, or the study site (permanent, temporary contract worker, or designee responsible for the conduct of the study), or is a family member (spouse, parent, sibling, or child) of the Sponsor, contract research organization, or study site employee.

Primary outcomes:
measure: Stage I: Number of Participants with Treatment Emergent Adverse Events Graded as Assessed by CTCAE Version 4.0
timeFrame: Up to Day 60
measure: Stage II: Percentage of Participants Who Were Alive (i.e., not died due to any reason) at Day 29
timeFrame: Day 29
Secondary outcomes:
measure: Stage I: Time to Improvement (2 points) in Clinical Status Assessment Using the World Health Organization 7-Point Ordinal Scale (WHO 7OS)
timeFrame: Up to Day 30
measure: 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])
timeFrame: Up to Day 30
measure: Stage I: Time to Improvement in Oxygenation for at least 48 hours
timeFrame: Up to Day 30
measure: Stage I: Change from Baseline in the World Health Organization (WHO)-7 Point Ordinal Scale
timeFrame: Baseline up to Day 30
measure: Stage I: Time to Discharge from Clinic or Hospital or to National Early Warning Score 2 (NEWS2) of <=2 and maintained for 24 hours
timeFrame: Up to Day 30
measure: Stage I: Percentage of Patients Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 30
timeFrame: Up to Day 30
measure: Stage I: Number of Days of Resting Respiratory Rate of more than 24 breath/min
timeFrame: Up to Day 30
measure: Stage I: Number of Days with Hypoxemia
timeFrame: Up to Day 30
measure: Stage I: Number of Days of Supplemental Oxygen use
timeFrame: Up to Day 30
measure: Stage I: Number of Ventilator-free Days
timeFrame: Up to Day 28
measure: Stage I: Number of Days in Intensive Care Unit (ICU)
timeFrame: Up to Day 30
measure: Stage I: Number of Days of Hospitalization for Survivors
timeFrame: Up to Day 30
measure: Stage I: Number of Participants with all cause Deaths
timeFrame: Up to Day 30
measure: Stage I: Percent Change from Baseline in Proinflammatory Cytokines
timeFrame: Baseline up to Day 30
measure: Stage I: Incidence of Drug-related Serious Adverse Events (SAEs)
timeFrame: Up to Day 60
measure: Stage II: Percentage of Participants Who Were Alive and free of Respiratory Failure
timeFrame: Up to Day 29
measure: Stage II: Percentage of Participants Alive and Free of Invasive Mechanical Ventilation
timeFrame: Up to Day 29
measure: Stage II: Percentage of Participants Alive and Discharged From the Hospital
timeFrame: Up to Day 29
measure: Stage II: Percentage of Participants Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 29
timeFrame: Up to Day 29
measure: Stage II: Percent Change from Baseline in Proinflammatory Biomarkers
timeFrame: Baseline up to Day 29
measure: Stage II: Number of Days in Intensive Care Unit (ICU)
timeFrame: Up to Day 29
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Research Site
state: California
city: Fort Lauderdale
country: United States
facility: Research site
state: Florida
city: Jacksonville
country: United States
facility: Research site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Baltimore
country: United States
facility: Research site
state: Maryland
city: Sioux Falls
country: United States
facility: Research Site
state: South Dakota
city: Amarillo
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
Study officials:
References: