Details

Details

Title 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

IRB ANSN1Z15

CC 15-545

Hospital Main Campus

Phase Phase 2

Disease Thrombotic Thrombocytopenic Purpura (TTP)

Drug DAS181

Description

Description

Primary Objective
  • To assess the mortality rate at Day 45 of DAS181-F02 in the hospitalized immunocompromised PIV infected lower tract subject population on supplemental oxygen.
Secondary Objective
  • To assess for clinical benefits based on:
    • Mortality rate at day 28
    • Change from baseline in viral load (log10 transformed) from Day 1 (baseline) to Day 2 through Day 10
    • Change in pulmonary function (FEV1% predicted) from Day 1 (baseline) to Day 2 through Day 10
Tertiary Objective
  • To assess the clinical impact of the DAS181 treatment in the immunocompromised PIV infected subject population on various clinical parameters
  • To assess the impact of DAS181 treatment on PIV viral load shedding.
Safety Objective
  • To assess the safety and tolerability of DAS181 treatment in the immunocompromised PIV infected population.
Exploratory Objective
  • The assessment of pharmacokinetics and immunogenicity.
Inclusion Criteria

Inclusion Criteria

  1. Age ≥12 years
  2. Able to provide informed consent, child assent with parental consent or surrogate consent when applicable
  3. Currently on invasive mechanical ventilation or noninvasive positive pressure ventilation (CPAP or bi-level positive airway pressure) or requiring > 2LPM supplemental oxygen therapy
  4. Immunocompromised, as defined by one of the following:
    • Autologous or Allogeneic hematopoietic stem cell transplantation (HSCT)
    • Lung or lung-heart transplantation
    • Subjects treated with chemotherapy for hematologic malignancies (e.g. leukemia, myeloma, lymphoma)
    • Subjects treated with chemotherapy for solid tumor malignancies
  5. Confirmed Parainfluenza virus at screening by one of the following methods using any sample type:
    • Respiratory virus panel
    • 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 subject on study).
  6. Confirmed PIV lower tract disease for subjects on mechanical ventilation within the 7 days of screening will be defined as one of the following:
    • PIV detection in bronchoalveolar lavage (BAL)
    • PIV detection in biopsy
    • PIV detection in tracheal aspirate AND a new pulmonary infiltrate or radiographic findings of bronchiolitis, pneumonitis or a worsening of an infiltrate or pneumonitis that temporally are associated with diagnosis of PIV infection on chest x-ray or CT
  7. Confirmed PIV lower tract disease for subjects on non-invasive positive pressure ventilation or ≥2L supplemental oxygen will be defined as all of the following within 7 days of screening:
    • New Pulmonary infiltrate or radiographic findings of bronchiolitis, pneumonitis or a worsening of an infiltrate or pneumonitis that temporally are associated with diagnosis of PIV infection on chest x-ray or CT
    • At least one PIV sign and/or symptom as defined in section 10.3.6; excluding hypoxia.
  8. ALT, AST or ALP are <3x ULN and TB are <2x ULN.
  9. 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.
  10. Male subjects must agree to use medically accepted form of contraception during the study period. Abstinence is an acceptable method of contraception.
Exclusion Criteria

Exclusion Criteria

  1. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance.
  2. Any significant finding in the subject's medical history or physical examination that, in the opinion of the investigator, would affect subject safety or compliance with the dosing schedule.
  3. In the opinion of the Investigator, subjects with a low chance of survival during the first 10 days of treatment.
  4. Subjects treated with oral, aerosolized or intravenous (IV) ribavirin for the treatment of PIV. A forty-eight hour (48 hr) washout period prior to randomization is allowed. Ribavirin treatment for current RSV and/or MPV is allowed and will not require washout.
  5. Subjects taking any investigational drug used to research or treat PIV
  6. Subjects with a history of allergic reactions to lactose.