E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Lower Respiratory Tract Parainfluenza Infection in Immunocompromised Subjects |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10033796 |
E.1.2 | Term | Parainfluenzae viral infections |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of DAS181 on clinical outcome compared to placebo as measured by percentage of RTRA Responders by Day 28 |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate all-cause mortality rate by Day 28 and 35 in DAS181 compared to placebo
2. To evaluate percent of patients who RTRA by Day 21 in DAS181 compared to placebo
3. To evaluate time (in days) to cessation of oxygen support in DAS181 compared to placebo
4. To evaluate rate of Clinical Stability (CS) by Day 28 in DAS181 compared to placebo
5. To determine the percent of subjects discharged each week (without mortality and hospice) up to Day 35 in DAS181 compared to placebo
6. To determine the initial length of stay (without mortality and hospice) in DAS181 compared to placebo
7. To evaluate total length of stay up to Day 35 in DAS181 compared to placebo
8. To evaluate PIV-related mortality rate by Day 28 and 35 in DAS181 compared to placebo |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Main/Parent Optional Pharmacokinetics Sub-Study Information Sheet
and Consent Form, version 2.0 dated 21Feb2019.
2. Pediatric Pharmacokinetic Sub-Study Assent Form (12–17 Years Old) Assent of a Minor to Be in an Investigational Study, version 2.0 dated 21Feb2019.
Objective is to investigate how the study drug is processed by the body by checking how much of the study drug is in the bloodstream at a particular point in time. |
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E.3 | Principal inclusion criteria |
Subjects must meet the following inclusion criteria at the time of randomization to be eligible for participation in this study:
1. Males and females ≥12 years of age
2. SpO2 < 92% on room air while at rest and requires supplemental oxygen ≥2 LPM at the time of randomization. Subjects who also require invasive mechanical ventilation (MV) or non-invasive positive pressure ventilation (CPAP or bi-PAP) are eligible, although ventilator support is not mandatory
3. 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
- Treated with chemotherapy for hematologic malignancies (e.g., leukemia, myeloma, lymphoma) at any time in the past
- Treated with chemotherapy for solid tumor malignancies (e.g., lung, breast, brain cancer) at any time in the past
4. Confirmed PIV lower tract disease for subjects within the screening period (3 days prior to randomization) will be defined as PIV detection in one of the following:
- bronchoalveolar lavage (BAL)
- lung biopsy
- upper respiratory viral sample:
o Tracheal aspirate OR sputum OR nasopharyngeal swab (NPS) OR nasopharyngeal wash
AND
o Radiographic finding of a new or worsening pulmonary infiltrate, bronchiolitis, OR pneumonitis that temporally is associated with diagnosis of PIV
infection on chest x-ray or CT scan.
PIV diagnosis test will use any of the sample types listed above and will be analyzed at local laboratory using one of the following methods:
- Respiratory virus panel (RVP),
- Qualitative/quantitative polymerase chain reaction (PCR) or
- Direct Fluorescent Antibody (DFA)
Note: If PIV infection is highly suspected but negative result with DFA, it is recommended to retest for PIV using RVP or PCR.
5. If female, patient must not be pregnant or nursing, and is either:
- Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral
oophorectomy, or hysterectomy; or
- Of childbearing potential and:
o Is practicing an effective method of contraception (e.g., oral/parenteral contraceptives or a barrier
method), or
o Has a vasectomized partner (at least 6 months postvasectomy
procedure), or
o Is currently abstinent from sexual intercourse, AND must have a negative serum (beta-human chorionic gonadotropin) pregnancy test at screening
Women of childbearing potential must be willing to practice the chosen contraceptive method or remain abstinent during the conduct of the study and for at least 30 days after last dose of study medication.
Acceptable methods of contraception include:
o Male or female condom with or without spermicides (a female condom should not be used at the same time as a male condom due to risk of tearing)
o Female barrier contraception (such as diaphragm, cervical cap, or sponge) with spermicide
o Continuous use of an intrauterine device for at least 90 days before the first dose of study drug
o Oral, implanted, injected, or vaginal hormonal contraceptives, if successfully used for at least 60 days before the first dose of study drug.
Additional contraception requirements may need to be followed according to local regulations and/or requirements.
6. Non-vasectomized males are required to practice effective birth control methods (e.g., abstinence, use of a condom or use of other barrier device) during the conduct of the study and for at least 30 days after last dose of study medication
7. Capable of understanding and complying with procedures as outlined in the protocol as judged by the Investigator and able to
sign informed consent form prior to the initiation of any screening or study-specific procedures. Subjects must have the ability to return to the hospital to comply with required procedures if they are discharged during the study.
Note: For subjects, including minors and patients with medical incapacity or impaired consciousness such that they are not able to give fully informed voluntary consent, the subjects' legal representative (parent, guardian or surrogate) must sign an institutional review board (IRB)/independent ethical committee (IEC)-approved informed consent document prior to the initiation of any screening or study specific procedures. Minor subjects must also sign an IRB/IEC-approved assent form unless not required per local and institution regulations |
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria will not be enrolled in this study:
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 treated with oral, aerosolized or intravenous (IV) ribavirin for the treatment of PIV within 48 hours prior to the first dose of study drug. Ribavirin treatment for current Respiratory Syncytial Virus (RSV) and/or Metapneumovirus (MPV) is allowed and will not require washout
3. Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN AND Total Bilirubin (TB) ≥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 assessment) due to known liver pathology including malignancy (primary or metastasis), chronic medications, transplantation, or chronic infection will not be excluded
4. Female subjects with positive serum pregnancy test, planning become pregnant, breastfeeding, or planning to breastfeed throughout the study period
5. Subjects taking any other investigational drugs used to research or treat PIV
6. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance
7. Subjects with known hypersensitivity to DAS181 and/or any of its components
8. Subjects with ongoing sepsis/septic shock |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent of subjects who RTRA |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
a. All-cause mortality rate
b. Percent of subjects who RTRA
c. Time (in days) to cessation of oxygen support
d. Percent of subjects who achieve CS
e. Percent of subjects discharged (without mortality or hospice)
f. Time (in days) to first hospital discharge (without hospice)
g. Total number of inpatients days
h. PIV-related mortality rate
i. PIV-related mortality rate
j. All-cause mortality rate |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a. at Day 28
b. by Day 21
c. in days
d. by Day 28
e. by Day 14,21,28 and 35
f. in days
g. up to Day 35
h. at Day 28
i. at Day 35
j. at Day 35 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
China |
Denmark |
France |
Germany |
Hong Kong |
Italy |
Korea, Republic of |
Spain |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |