Phase III DAS181 Lower Tract PIV Infection in Immunocompromised Subjects (Substudy: DAS181 for COVID-19): RCT Study

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03808922
• Other study ID #: DAS181-3-01
• Secondary ID: 2018-004318-16
• Status: Recruiting
• Phase: Phase 3
• Start date: May 23, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: Ansun Biopharma, Inc.
• Contact: Lisa Li
• Phone: 858-353-4948
• Email: lli[@]ansunbiopharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 274
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19
• Immunocompromised
• Infections
• Lower Respiratory Tract Infection
• Parainfluenza
• Paramyxoviridae Infections
• Respiratory Tract Infections

Intervention

Drug:
• DAS181
DAS181 4.5mg nebulized qd x 7 OR 10 days
• Placebo
Placebo nebulized qd x 7 OR 10 days
• DAS181 COVID-19
DAS181 4.5mg nebulized q12h/day x 7 OR 10 days
• DAS181 OL
DAS181 4.5mg nebulized qd x 7 OR 10 days = 40kg DAS181 2.5mg nebulized qd x 7 OR 10 days < 40kg

Locations

Country	Name	City	State
Australia	The Wesley Hospital	Auchenflower	Queensland
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	Westmead Hospital	Sydney	New South Wales
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	Shanghai Pulmonary Hospital	Yangpu	Shanghai
Denmark	Rigshospitalet	Copenhagen
France	Hôpital Henri Mondor	Créteil	Ile-de-France
Hong Kong	Prince of Wales Hospital	Sha Tin	New Territories
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul	Gyeonggi-do
Korea, Republic of	Seoul National University Hospital	Seoul	Gyeonggi-do
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul	Gyeonggi-do
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Zhongzheng	Taipei City
United States	Universtiy of Michigan	Ann Arbor	Michigan
United States	Children's Hospital Colorado	Aurora	Colorado
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The Lindner Center- The Christ Hospital	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	City of Hope cancer Center	Duarte	California
United States	Duke University	Durham	North Carolina
United States	University of Kansas Medical Center	Fairway	Kansas
United States	Cook Children's	Fort Worth	Texas
United States	Texas Health	Fort Worth	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	MD Anderson	Houston	Texas
United States	Therapeutic Concepts	Houston	Texas
United States	UCLA	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Froedtert Medical College Pulmonary Clinic	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	VCU Health System	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of California Davis Health System	Sacramento	California
United States	Washington University	Saint Louis	Missouri
United States	University of California San Diego Medical Center	San Diego	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Children's Hospital	Seattle	Washington
United States	Louisiana State University	Shreveport	Louisiana
United States	Kent Hospital	Warwick	Rhode Island
United States	Novant Health	Winston-Salem	North Carolina
United States	St. Elizabeth Youngstown Hospital	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ansun Biopharma, Inc.

Countries where clinical trial is conducted

United States,  Australia,  China,  Denmark,  France,  Hong Kong,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of subjects who Return to Room Air (RTRA) (main study)	Removal of all oxygen support (with stable SpO2)	by Day 28
Primary	Percent of subjects with improved COVID-19 Clinical Status Scale (sub-study)		Day 14
Secondary	All-cause mortality rate (main study)		at Day 28
Secondary	Percent of subjects who Return to Room Air (RTRA) (main study)		by Day 21
Secondary	Time (in days) to RTRA (main study)		Days 10, 14, 21, 28
Secondary	Percent of subjects who achieve clinical stability (main study)		by Day 28
Secondary	Percent of subjects discharged (without mortality and hospice) (main study)		by Days 14, 21, 28 and 35
Secondary	Time (in days) to first hospital discharge (without hospice) (main study)		through Day 35
Secondary	Total number of inpatient days (main study)		up to Day 35
Secondary	Baseline SAD-RV infection-related mortality rate (main study)		at Day 28
Secondary	Baseline SAD-RV infection-related mortality rate (main study)		at Day 35
Secondary	All-cause mortality rate (main study)		at Day 35
Secondary	Change in pulmonary function (FEV1% predicted) (main study)		Day 1, Day 7, Day 14, Day 28
Secondary	Time to improved COVID19 clinical status (Sub-study)		Day 5, Day 10, Day 21, Day 28
Secondary	Time to RTRA		Day 10, Day 14, Day 21, Day 28
Secondary	Time to Clinical stability		Day 14, Day 21, Day 28
Secondary	Time to SARS-CoV-2 RNA in the respiratory specimens being undetectable		Day 5, Day 10, Day 14, Day 21, Day 28
Secondary	Time to Clinical deterioration		Day 5, Day 10, Day 14, Day 21, Day 28
Secondary	Time to Discharge from hospital (without readmission before Day 28).		Day 14, Day 21, Day 28
Secondary	Time to Death (all causes)		Day 14, Day 21, Day 28