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

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

Official Title
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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

Conditions
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Parainfluenza

Intervention / Treatment
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* Drug: DAS181 dry powder, formulation F02
* Drug: Lactose Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAS181<br>DAS181-F02, 4.5 mg qd x 10 days | Drug: DAS181 dry powder, formulation F02<br> <br> |
| Placebo Comparator: Lactose Placebo<br>placebo, 4.5 mg qd x 10 days | Drug: Lactose Placebo<br> <br> |

What is the study measuring?
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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 |