Clinical trial NCT03808922: Phase III DAS181 Lower Tract PIV Infection in Immunocompromised Subjects (Substudy: DAS181 for COVID-19): RCT Study
Official title: A Phase III Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Lower Respiratory Tract Parainfluenza Infection in Immunocompromised Subjects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lower Respiratory Tract Infection
Parainfluenza
Immunocompromised
COVID-19
Keywords: Parainfluenza
PIV
Immunocompromised
Lower Respiratory Tract Infection
LRTI
COVID19
SARS-CoV-2
Coronavirus
Ansun
Lead sponsor: Ansun Biopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-18
Enrollment: 274
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will seek to enroll immunocompromised patients with Lower Tract parainfluenza infection.

It also contains a sub-study to enroll patients with severe COVID-19.

Detailed description: Eligible subjects (i.e., those meeting the Inclusion / Exclusion criteria) will be enrolled in one of four cohorts based on the following criteria:

Cohort 1:

All eligible subjects in the PoI who are ≥18 year old subjects with a PIV infection and meet all of the following criteria:

1.1 Meet criteria for being severely immunocompromised 1.2 Prior to the onset of PIV infection, had no ongoing need for oxygen therapy due to a chronic respiratory condition (e.g., COPD, sleep apnea) and are assessed as acutely hypoxemic due to their PIV infection 1.3 At the time of randomization are not on mechanical, bi-level or continuous positive airway pressure (Bi-PAP or CPAP) ventilation 1.4 Have no known concurrent respiratory viral coinfection(s)

Cohort 2:

All eligible subjects in the PoI who are ≥18 year old with a PIV infection (including those with PIV and another SAD-RV) who do not meet one or more of the listed criteria for Cohort 1.

Cohort 3:

All eligible subjects in the PoI who are \<18 year old subjects with a PIV infection (including those with PIV and another concurrent SAD-RV). There is no lower age limit for this cohort.

Cohort 4:

All eligible subjects in the PoI with a respiratory infection due to any SAD-RV infection except PIV. Eligible subjects with both PIV and an additional concurrent SAD-RV, will be enrolled for either Cohorts 2 or 3 depending on their age. There is no lower age limit for this cohort.

Sub-Study:

Patients with Severe COVID-19

Eligibility criteria: Inclusion Criteria:

1. At the time of randomization, requires supplemental oxygen ≥2 LPM due to hypoxemia.
2. Immunocompromised, as defined by one or more of the following:

   * Received an autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at any time in the past
   * Received a solid organ transplant at any time in the past
   * Has been or is currently being treated with chemotherapy for hematologic malignancies (e.g., leukemia, myeloma, lymphoma) and/or solid tumor malignancies (e.g., lung, breast, brain cancer) at any time in the past
   * Has an immunodeficiency due to congenital abnormality (only applicable to subjects age \< 18 years old) or pre-term birth (only applicable to subjects age ≤ 2 years old)
3. Has, within 3 days prior to randomization, a confirmed LRTI with a sialic acid dependent respiratory virus
4. If female, subject must meet one of the following conditions:

   * Not be of childbearing potential or
   * Be of childbearing potential and have a negative urine/serum pregnancy test and agrees to practice an acceptable method of contraception
5. Non-vasectomized males are required to practice effective birth control methods
6. Capable of understanding and complying with procedures as outlined in the protocol
7. Provides signed informed consent prior to the initiation of any screening or study-specific procedures

For COVID-19 sub study:

1. Be ≥18 years of age
2. Provide adequate medical history to permit accurate stratification (but health status may be healthy, high-risk conditions, or immunocompromised).
3. Prior to SARS CoV 2 infection, has the ability to carry out self-care activities of daily living (basic ADL)
4. Have lower respiratory tract infection (LRTI) confirmed by CT imaging, with or without contrast, to involve at least 2 lobes of the lung.
5. Has laboratory-confirmation of the presence of SARS CoV 2 in the respiratory tract by at least one of the following samples
6. Satisfy inclusion criteria #1, 4, 5, 6, 7 of the main study

Exclusion Criteria:

1. Subjects may not be on hospice care or, in the opinion of the investigator, have a low chance of survival during the first 10 days of treatment
2. Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN and Total Bilirubin (TBILI) ≥2x ULN Note: Subjects with ALT/AST/ALP ≥ 3x ULN AND TB ≥2x ULN that have been chronically stable (for \>1 year on more than one assessments) due to known liver pathology including malignancy (primary or metastasis), chronic medications, transplantation, or chronic infection will not be excluded
3. Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug
4. Subjects taking any other investigational drug used to treat pulmonary infection.
5. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance
6. Subjects with known hypersensitivity to DAS181 and/or any of its components
7. Subjects with severe sepsis due to either their baseline SAD-RV infection or a concurrent viral, bacterial, or fungal infection and meet at least one of the following criteria:

   * Has evidence of vital organ failure outside of the lung (e.g., liver, kidney)
   * Requires vasopressors to maintain blood pressure

For COVID-19 sub study:

1. Subjects requiring invasive mechanical, Bi-PAP or CPAP ventilation at randomization.
2. Subjects receiving any other investigational or empiric treatment for SARS-2-CoV (either as part of a clinical trial or under emergency approval (approved agents for the management of symptoms, e.g., fever, are permitted).
3. Subjects who are known HIV-positive (and not undetectable at most recent HIV RNA assessment)
4. Subjects who are currently taking immunomodulating biologics (e.g, interferons, interleukin)
5. Subjects with severe sepsis due to either their SARS-CoV-2 infection or a concurrent viral, bacterial, or fungal infection and meeting at least one of the following criteria:

   * Have evidence of vital organ failure outside of the lung (e.g., liver, kidney)
   * Require vasopressors to maintain blood pressure
6. Subjects meeting exclusion criteria #2, 3, 5 and 6 of the main study

Primary outcomes:
measure: Percent of subjects who Return to Room Air (RTRA) (main study)
timeFrame: by Day 28
measure: Percent of subjects with improved COVID-19 Clinical Status Scale (sub-study)
timeFrame: Day 14
Secondary outcomes:
measure: All-cause mortality rate (main study)
timeFrame: at Day 28
measure: Percent of subjects who Return to Room Air (RTRA) (main study)
timeFrame: by Day 21
measure: Time (in days) to RTRA (main study)
timeFrame: Days 10, 14, 21, 28
measure: Percent of subjects who achieve clinical stability (main study)
timeFrame: by Day 28
measure: Percent of subjects discharged (without mortality and hospice) (main study)
timeFrame: by Days 14, 21, 28 and 35
measure: Time (in days) to first hospital discharge (without hospice) (main study)
timeFrame: through Day 35
measure: Total number of inpatient days (main study)
timeFrame: up to Day 35
measure: Baseline SAD-RV infection-related mortality rate (main study)
timeFrame: at Day 28
measure: Baseline SAD-RV infection-related mortality rate (main study)
timeFrame: at Day 35
measure: All-cause mortality rate (main study)
timeFrame: at Day 35
measure: Change in pulmonary function (FEV1% predicted) (main study)
timeFrame: Day 1, Day 7, Day 14, Day 28
measure: Time to improved COVID19 clinical status (Sub-study)
timeFrame: Day 5, Day 10, Day 21, Day 28
measure: Time to RTRA
timeFrame: Day 10, Day 14, Day 21, Day 28
measure: Time to Clinical stability
timeFrame: Day 14, Day 21, Day 28
measure: Time to SARS-CoV-2 RNA in the respiratory specimens being undetectable
timeFrame: Day 5, Day 10, Day 14, Day 21, Day 28
measure: Time to Clinical deterioration
timeFrame: Day 5, Day 10, Day 14, Day 21, Day 28
measure: Time to Discharge from hospital (without readmission before Day 28).
timeFrame: Day 14, Day 21, Day 28
measure: Time to Death (all causes)
timeFrame: Day 14, Day 21, Day 28
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center, University of Miami Health System
state: Florida
city: Tampa
country: United States
facility: Houston Methodist Hospital
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Shreveport
country: United States
facility: Louisiana State University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Universtiy of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center- The Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Youngstown
country: United States
facility: St. Elizabeth Youngstown Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Health System
state: Pennsylvania
city: Warwick
country: United States
facility: Kent Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's
state: Texas
city: Fort Worth
country: United States
facility: Texas Health
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Richmond
country: United States
facility: VCU Health System
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Medical College Pulmonary Clinic
state: Wisconsin
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: The Wesley Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Yangpu
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
city: Hangzhou
country: China
facility: Shulan (Hangzhou) Hospital co., LTD
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Créteil
country: France
facility: Hôpital Henri Mondor
state: Ile-de-France
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
state: Gyeonggi-do
city: Zhongzheng
country: Taiwan
facility: National Taiwan University Hospital
state: Taipei City
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
affiliation: Ansun Biopharma, Inc.
name: Lisa Li
role: STUDY_DIRECTOR
References: