Phase III DAS181 Lower Tract PIV Infection in Immunocompromised Subjects (Substudy: DAS181 for COVID-19): RCT Study
- Conditions
- Lower Respiratory Tract InfectionParainfluenzaImmunocompromisedCOVID-19
- Interventions
- Registration Number
- NCT03808922
- Lead Sponsor
- Ansun Biopharma, Inc.
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 274
-
At the time of randomization, requires supplemental oxygen ≥2 LPM due to hypoxemia.
-
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)
-
Has, within 3 days prior to randomization, a confirmed LRTI with a sialic acid dependent respiratory virus
-
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
-
Non-vasectomized males are required to practice effective birth control methods
-
Capable of understanding and complying with procedures as outlined in the protocol
-
Provides signed informed consent prior to the initiation of any screening or study-specific procedures
For COVID-19 sub study:
- Be ≥18 years of age
- Provide adequate medical history to permit accurate stratification (but health status may be healthy, high-risk conditions, or immunocompromised).
- Prior to SARS CoV 2 infection, has the ability to carry out self-care activities of daily living (basic ADL)
- Have lower respiratory tract infection (LRTI) confirmed by CT imaging, with or without contrast, to involve at least 2 lobes of the lung.
- Has laboratory-confirmation of the presence of SARS CoV 2 in the respiratory tract by at least one of the following samples
- Satisfy inclusion criteria #1, 4, 5, 6, 7 of the main study
-
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
-
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
-
Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug
-
Subjects taking any other investigational drug used to treat pulmonary infection.
-
Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance
-
Subjects with known hypersensitivity to DAS181 and/or any of its components
-
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:
-
Subjects requiring invasive mechanical, Bi-PAP or CPAP ventilation at randomization.
-
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).
-
Subjects who are known HIV-positive (and not undetectable at most recent HIV RNA assessment)
-
Subjects who are currently taking immunomodulating biologics (e.g, interferons, interleukin)
-
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
-
Subjects meeting exclusion criteria #2, 3, 5 and 6 of the main study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 and Cohort 2 Treatment DAS181 DAS181 4.5mg qd x 7 OR 10 days Cohort 1 and Cohort 2 Placebo Placebo Placebo qd x 7 OR 10 days Cohort 3 DAS181 OL DAS181 4.5mg qd x 7 OR 10 days (≥ 40 kg) DAS181 2.5mg qd x 7 OR 10 days (\< 40kg) Cohort 4 DAS181 OL DAS181 4.5mg qd x 7 OR 10 days DAS181 COVID-19 Treatment DAS181 COVID-19 DAS181 4.5mg q12h x 7 OR 10 days DAS181 COVID-19 Placebo Placebo Placebo q12h x 7 OR 10 days
- Primary Outcome Measures
Name Time Method Percent of subjects with improved COVID-19 Clinical Status Scale (sub-study) Day 14 Percent of subjects who Return to Room Air (RTRA) (main study) by Day 28 Removal of all oxygen support (with stable SpO2)
- Secondary Outcome Measures
Name Time Method Baseline SAD-RV infection-related mortality rate (main study) at Day 35 Percent of subjects who Return to Room Air (RTRA) (main study) by Day 21 Percent of subjects who achieve clinical stability (main study) by Day 28 Percent of subjects discharged (without mortality and hospice) (main study) by Days 14, 21, 28 and 35 Time (in days) to first hospital discharge (without hospice) (main study) through Day 35 All-cause mortality rate (main study) at Day 35 Time to Clinical stability Day 14, Day 21, Day 28 Time (in days) to RTRA (main study) Days 10, 14, 21, 28 Total number of inpatient days (main study) up to Day 35 Time to RTRA Day 10, Day 14, Day 21, Day 28 Time to SARS-CoV-2 RNA in the respiratory specimens being undetectable Day 5, Day 10, Day 14, Day 21, Day 28 Time to Discharge from hospital (without readmission before Day 28). Day 14, Day 21, Day 28 Time to Death (all causes) Day 14, Day 21, Day 28 Change in pulmonary function (FEV1% predicted) (main study) Day 1, Day 7, Day 14, Day 28 Time to improved COVID19 clinical status (Sub-study) Day 5, Day 10, Day 21, Day 28 Time to Clinical deterioration Day 5, Day 10, Day 14, Day 21, Day 28
Trial Locations
- Locations (66)
MD Anderson
🇺🇸Houston, Texas, United States
Sylvester Comprehensive Cancer Center, University of Miami Health System
🇺🇸Miami, Florida, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Iowa Health Care
🇺🇸Iowa City, Iowa, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
City of Hope cancer Center
🇺🇸Duarte, California, United States
UCLA
🇺🇸Los Angeles, California, United States
University of California Davis Health System
🇺🇸Sacramento, California, United States
University of California San Diego Medical Center
🇺🇸San Diego, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University of Kansas Medical Center
🇺🇸Fairway, Kansas, United States
Louisiana State University
🇺🇸Shreveport, Louisiana, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Universtiy of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
Novant Health
🇺🇸Winston-Salem, North Carolina, United States
The Lindner Center- The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
St. Elizabeth Youngstown Hospital
🇺🇸Youngstown, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center Health System
🇺🇸Pittsburgh, Pennsylvania, United States
Kent Hospital
🇺🇸Warwick, Rhode Island, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Cook Children's
🇺🇸Fort Worth, Texas, United States
Texas Health
🇺🇸Fort Worth, Texas, United States
Therapeutic Concepts
🇺🇸Houston, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
VCU Health System
🇺🇸Richmond, Virginia, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Froedtert Medical College Pulmonary Clinic
🇺🇸Milwaukee, Wisconsin, United States
Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
The Wesley Hospital
🇦🇺Auchenflower, Queensland, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Shanghai Pulmonary Hospital
🇨🇳Yangpu, Shanghai, China
West China Hospital
🇨🇳Chengdu, Sichuan, China
Shulan (Hangzhou) Hospital co., LTD
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Rigshospitalet
🇩🇰Copenhagen, Denmark
Hôpital Henri Mondor
🇫🇷Créteil, Ile-de-France, France
Prince of Wales Hospital
🇭🇰Sha Tin, New Territories, Hong Kong
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
National Taiwan University Hospital
🇨🇳Zhongzheng, Taipei City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan