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 as measured by frequency of return to room air (RTRA) responders compared to placebo |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of DAS181 on the frequency and rate of return to room air (RTRA) compared to placebo
To evaluate the effect of DAS181 on mortality (all-cause and pulmonary infection-related) compared to placebo
To evaluate the effect of DAS181 on the frequency and rate of return to Clinical Stability (CS) compared to placebo
To evaluate the effect of DAS181 on the length of initial hospital stay and of total days of hospitalization compared to placebo
To evaluate the effect of DAS181 on pulmonary function 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 all of the following inclusion criteria to be eligible for participation in this study: 1. Requires, at the time of randomization, supplemental oxygen ≥2 LPM due to hypoxemia, defined by meeting at least one of the following criteria: - SpO2 <92% on or off supplemental oxygen - mechanical or non-invasive ventilation (CPAP or Bi-PAP) - Written declaration from Investigator that subject is clinically hypoxemic and removal of oxygen supplementation would not be considered clinically appropriate for the purpose of measuring SpO2 while on room air Note: Documentation of hypoxemia prior to or during the most recent oxygen supplementation must be available in source documents. Note: 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 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 (SAD-RV, see definition). This can be confirmed by: - bronchoalveolar lavage (BAL) positive for SAD-RV - lung biopsy positive for SAD-RV - chest imaging with a new or worsening finding of pulmonary infiltrate, bronchiolitis, or pneumonitis temporally associated with an upper respiratory tract sample (e.g., tracheal aspirate, sputum, nasopharyngeal swab (NPS), nasopharyngeal wash) positive for SAD-RV Note: These requirements can be fulfilled by results from samples and/or chest imaging that are collected/performed locally as per standard of care within 3 days prior to randomization. Note: For all subjects, after obtaining informed consent but within 3 days prior to randomization, a separate nasopharyngeal swab sample will be collected and sent to the central laboratory for confirmation of a SAD-RV. The results from the central lab analysis are not required to initiate the subject on study treatment. 4. If female, subject must meet one of the following conditions: - Not be of childbearing potential, defined as one or more of the following conditions: -Premenarchal -Postmenopausal for at least 1 year -Surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; - Be of childbearing potential and meet all of the following criteria: -Has a negative urine or serum pregnancy test (beta-human chorionic gonadotropin) at screening -Agrees to practice an acceptable method of contraception (or meets criteria for waiving contraception) from screening until at least 30 days after last dose of study medication (see Section 8.10.1) for details) Note: Additional contraception requirements may need to be followed according to local regulations and/or requirements. 5. Non-vasectomized males are required to practice effective birth control methods (see Section 8.10.1) from screening until at least 30 days after last dose of study medication 6. 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 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 TBILI ≥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 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 drugs 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), or Requires vasopressors to maintain blood pressure |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent of subjects who ‘Return to Room Air’ by Day 28 |
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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 at Day 28 b. Percent of subjects who RTRA by Day 21 c. Time (in days) to RTRA d. Percent of subjects who achieve CS by Day 28 e. Percent of subjects discharged (without mortality or hospice) by Day 14, 21, 28 and 35 f. Time (in days) to first hospital discharge (without mortality or hospice) g. Total number of inpatients days (up to Day 35) h. Mortality at Day 28 related to baseline SAD-RV infection i. Mortality at Day 35 related to baseline SAD-RV infection j. All-cause mortality rate at Day 35 k. Change in pulmonary function (FEV1% predicted) from Day 1 (baseline) to Day 7, Day 14 and Day 28 |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
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 |