A Phase II, Randomized, Double-blind, Placebo-controlled Study to Examine the Effects of DAS181 in Immunocompromised Subjects With Lower Respiratory Tract Parainfluenza Infection on Supplemental Oxygen (DAS181-2-05)

This protocol will seek to enroll immunocompromised patients who are on supplemental oxygen and diagnosed with a parainfluenza infection.

Study Overview

• Status: Completed
• Conditions: Parainfluenza
• Intervention / Treatment: Drug: DAS181 dry powder, formulation F02; Drug: Lactose Placebo

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic-Arizona
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94305
      • Stanford University Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis
    • San Diego, California, United States, 92121
      • Ansun Biopharma, Inc
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 42367
      • Indiana Blood and Marrow Transplantation
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas
    • Kansas City, Kansas, United States, 64108
      • Children's Mercy Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minnesota City, Minnesota, United States, 55455
      • University of Minnesota, School of Medicine
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College/New York Presbyterian Hospital
    • New York, New York, United States, 10065
      • Weill Cornell Medical College-Peds
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Stony Brook, New York, United States, 11794-88183
      • StonyBrook
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt- Henry-Joyce Cancer Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cencer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥12 years
• Able to provide informed consent, child assent with parental consent or surrogate consent when applicable
• Currently on invasive mechanical ventilation or noninvasive positive pressure ventilation (CPAP or bilevel positive airway pressure) or requiring > 2LPM supplemental oxygen therapy to maintain O2 saturation > 90% due to hypoxemia
• Immunocompromised, as defined by one of the following: Autologous or Allogeneic hematopoietic cell transplantation (HSCT); Lung or lung-heart transplantation; Subjects treated with chemotherapy for hematologic malignancies; Subjects treated with chemotherapy for solid tumor malignancies
• Confirmed parainfluenza at screening by one of the following methods using any sample type: Respiratory Virus Panel, Direct fluorescent antibody (DFA), Qualitative/quantitative RT-PCR test for parainfluenza virus performed at the local laboratory (a confirmatory PCR test will be done at the central lab but is not required to start the patient on study).
• Confirmed PIV lower tract disease for subjects on mechanical ventilation will be defined as PIV detection in bronchoalveolar lavage (BAL) or biopsy within last 7 days of screening
• Confirmed PIV lower tract disease for subjects on non-invasive positive pressure ventilation or supplemental oxygen will be defined as all of the following within the last 7 days of screening: New pulmonary infiltrate on chest imaging and at least one PIV sign and/or symptom as defined in section 10.3.6
• Female subjects of child-bearing potential who are capable of conception must be post-menopausal (one year or greater without menses), surgically incapable of childbearing, or practicing two effective methods of birth control. Acceptable methods include abstinence, intrauterine device, spermicide, barrier, male partner surgical sterilization and hormonal contraception. A female subject ≥18 years of age and of child bearing potential must agree to practice two acceptable methods of birth control during the study period. All reproductive female subjects must have a negative serum pregnancy test during the screening visit.
• Male subjects must agree to use medically accepted form of contraception during the study period. Abstinence is an acceptable method of contraception.

Exclusion Criteria:

• Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect patient safety and/or compliance.
• Any significant finding in the patient's medical history or physical examination that, in the opinion of the investigator, would affect patient safety or compliance with the dosing schedule.
• In the opinion of the Investigator, subjects with a low chance of survival during the first 5 days of treatment.
• Subjects treated with oral, aerosolized or intravenous (IV) ribavirin for the treatment of PIV. A forty-eight hour (48 hr) wash out period prior to randomization is allowed.
• Subjects with a history of RSV or MPV
• Subjects taking any other investigational drug used to research or treat PIV.
• Subjects with a history of allergic reactions to lactose.
• Subjects with a history of documented Pseudomonas aeruginosa pneumonia confirmed radiographically and by culture from BAL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DAS181; DAS181-F02, 4.5 mg qd x 10 days	Drug: DAS181 dry powder, formulation F02
PLACEBO_COMPARATOR: Lactose Placebo; placebo, 4.5 mg qd x 10 days	Drug: Lactose Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Stability	Clinical stability survival (CSS) rate is defined as subjects who meet the clinical stability criteria and are alive at Study Day 45 (Responders) compared to those who have not met clinical stability criteria or have expired regardless of stability status (Non-responders)	45 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Stability	Clinical stability (CS) rate excluding survival status: Clinical stability (CS) rate is defined as subjects who reached clinical stability criteria (Responders) compared to those subjects who did not meet the clinical stability criteria (Non-responders).	45 days
Mortality	Mortality rate at Day 45	45 days
Clinical Stability	Time (in days) to reach clinical stability (including survival status or excluding survival status)	45 days
Clinical Stability	Time (in days) to death	45 days
Clinical Stability	Time (in days) to hospital discharge of CS non-responders and death	45 days

Collaborators and Investigators

• Sponsor: Ansun Biopharma, Inc.

Publications and helpful links

General Publications

• Chemaly RF, Marty FM, Wolfe CR, Lawrence SJ, Dadwal S, Soave R, Farthing J, Hawley S, Montanez P, Hwang J, Ho JH, Lewis S, Wang G, Boeckh M. DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study. Clin Infect Dis. 2021 Aug 2;73(3):e773-e781. doi: 10.1093/cid/ciab113.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): December 15, 2016
• Study Completion (ACTUAL): December 15, 2016

Study Registration Dates

• First Submitted: July 17, 2012
• First Submitted That Met QC Criteria: July 18, 2012
• First Posted (ESTIMATE): July 19, 2012

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2017
• Last Update Submitted That Met QC Criteria: September 21, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Paramyxoviridae Infections
• Other Study ID Numbers: DAS181-2-05