A Study of ALS-008176 in Infants Hospitalized with RSV

Phase 1

• Conditions: Respiratory Syncytial Virus (RSV) Infection; MedDRA version: 18.0Level: PTClassification code 10061603Term: Respiratory syncytial virus infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2013-005104-33-FR
• Lead Sponsor: Alios BioPharma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-22
• Last Update Posted: 19 March 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 264

Inclusion Criteria

1) Subject’s parent(s)/legal guardian(s) has provided signed and dated informed consent and authorization to use protected health information, as required by national and local regulations.
2) In the investigator’s opinion, the subject’s parent(s)/legal guardian(s) understands and is able to comply with protocol requirements, instructions, and protocol-stated restrictions, and is likely to complete the study as planned.
3) Male or female infant who
• is = 1.0 to = 12.0 months of age (inclusive), defined at the time of hospital admission
• has been diagnosed with RSV infection based on study-supplied BINAX NOW RSV test. NOTE: A subject remains eligible if the BINAX NOW RSV result is negative but a RSV-specific PCR assay run locally is positive. (RSV-specific PCR run locally is not required.) Coinfection with other respiratory viruses or bacterial coinfection in addition to RSV is permissible.
• has been hospitalized for < 48 hours for confirmed RSV infection
• has had symptoms consistent with RSV infection (e.g., runny nose, cough, sneezing, fever, and tachypnea) for = 5days
4) With the exception of the RSV-related illness, the subject is in otherwise good health as deemed by the investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests, and ECG
5) Creatinine clearance is within the normal range for the subject’s age (Schwartz equation)
Are the trial subjects under 18? yes
Number of subjects for this age range: 264
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) History of or concurrent clinically significant medical illness (not directly attributable to the acute RSV infection) – including, but not limited to cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, endocrinologic, immunologic, musculoskeletal, oncologic, or congenital disorders – as judged by the Investigator. Specifically excluded conditions include but are not limited to:
a. Immunosuppressed state
b. Bronchopulmonary dysplasia
c. Congenital heart disease
d. Down’s syndrome
2) Prematurity, defined as gestational age < 37 weeks at birth
3) Body weight <10th percentile for age
4) Subjects receiving invasive endotracheal mechanical ventilation
5) Subjects who are thought to have a poorly functioning gastrointestinal tract (i.e., unable to absorb drugs or nutrition via enteral route). NOTE: The use of intravenous fluids is not exclusionary so long as the investigator believes the patient’s gastrointestinal tract still functions properly (i.e., is able to absorb drugs or nutrition).
6) Subjects with clinically significant laboratory abnormalities which are deemed by the Investigator to represent a safety risk to participation in this study. Other laboratory parameters outside the reference range for the subject’s age may be included if the investigator considers the abnormalities unlikely to introduce additional risk factors and will not interfere with data interpretation. A single repeat laboratory evaluation is allowed for eligibility determination.
7) Any condition that, in the opinion of the investigator, would compromise the study or the well-being of the subject or prevent the subject from meeting the study requirements
8) Clinically significant abnormal ECG findings, as judged by the Investigator
9) Subjects anticipated to be discharged from the hospital in < 24 hours from the time of randomization
10) Exclusionary medications include:
• Herbal supplements within 21 days prior to randomization
• The following prescription medications:
a) Any chronically used, systemic prescription medications
b) Use of systemic medications (either chronically or within the 21 days prior to randomization) which are known to modulate the host immune response and/or increase viral shedding such as corticosteroids or other immunomodulatory therapies
c) Prescription medications used within 14 days prior to randomization to treat the RSV infection itself (e.g., ribavirin, intravenous immunoglobulin). Prescription medications intended to treat the symptoms/sequelae of the RSV infection are permitted.
d. Prescription medications which are known to be a strong inducer or inhibitor of CYP450 enzymes, within 21 days prior to randomization

• Investigational drug trial medications within 30 days or 5 half-lives (whichever is longer) prior to randomization
• Prior exposure to an investigational vaccine
• MMR vaccine within 1 week prior to screening, according to parent report
• Prior exposure to ALS-008176
• Prior exposure to palivizumab
11) Infants who are breastfeeding and their mother is taking any of the exclusionary medications described in exclusion criterion 10.
12) Infants with another child in the household who has enrolled in the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of single and multiple doses of ALS-008176;Secondary Objective: • To evaluate the pharmacokinetics of ALS-008112 and ALS-008144 (and other metabolites, if applicable) in blood following single and multiple doses of ALS-008176<br>• To evaluate the antiviral activity of ALS-008176 after single and multiple doses of ALS-008176<br>• To determine if ALS-008176 exposure results in the emergence of resistant strains of RSV;Primary end point(s): Safety data including, but not limited to, adverse events, physical examinations, vital signs, 12-lead ECGs and clinical laboratory results (including chemistry and hematology);Timepoint(s) of evaluation of this end point: SAD: Post randomisation, Study days 2 to 6 and Completion visit day 7<br>MAD: Post randomisation, Study days 2 to 10, Outpatient safety visit and Completion day 11.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • PK parameters of ALS-008112 and ALS-008144 (and other metabolites, as applicable) in blood following single dose administration: Cmax, tmax, t1/2, CL/F and Vdss/F (excluding metabolites), AUC0-24h, AUC0-inf or AUC<br>• PK parameters of ALS-008112 and ALS-008144 (and other metabolites as applicable) in blood following repeat dose administration: Cmax, Cmin, tmax, t1/2, CL/F and Vdss/F (excluding metabolites), AUC0-12h, AUC0-24h, AUC0-tau, AUC0-inf or AUC0-last<br>• RSV viral RNA concentrations in nasal aspirates as measured by quantitative RT-PCR<br>• Changes in the RSV polymerase that result in reduced sensitivity to ALS-008112;Timepoint(s) of evaluation of this end point: SAD: Post randomisation, Study days 2 to 6 and Completion visit day 7<br>MAD: Post randomisation, Study days 2 to 10, Outpatient safety visit and Completion day 11.