A Study of ALS-008176 in Infants Hospitalized with RSV

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2013-005104-33-GB
• Date of registration: 13/01/2014
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• Public title: A Study of ALS-008176 in Infants Hospitalized with RSV
• Scientific title: A Randomized, Double-blind, Placebo-controlled, 2-Part Study of Orally Administered ALS-008176 to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Dosing and Multiple Ascending Dosing in Infants Hospitalized with Respiratory Syncytial Virus (RSV) Infection
• Date of first enrolment: 14/02/2014
• Target sample size: 260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005104-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Chile, Colombia, France, Japan, New Zealand, Panama, Romania, South Africa, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: None
• Affiliation: Janssen Research & Development, LLC

• Name: None
• Affiliation: Janssen Research & Development, LLC

Key inclusion & exclusion criteria

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 or <28 days of age (neonate cohort only). Note: all subjects, including neonates, must have been discharged from the hospital after birth and are now being admitted due to an RSV related illness
• has been diagnosed with RSV infection based on study-supplied BINAX NOW RSV test or an RSV PCR or any other RSV assay conducted at the clinical trial site. NOTE: A subject remains eligible if any RSV result is positive. (RSV-specific PCR run locally is strongly encouraged, but not required.) Coinfection with other respiratory viruses or bacterial coinfection in addition to RSV is permissible.
• has been hospitalized for < 96 hours (at the time of randomization) for confirmed RSV infection (NOTE: nosocomial RSV infection is excluded)
• has had symptoms consistent with RSV infection (e.g., runny nose, cough, sneezing, fever, or tachypnea) for =5 days at the time of randomization (unless otherwise instructed by the IDMC which may modify the duration to up to 7 days)
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 not below the lower limit of normal for the subject’s age (Schwartz equation calculation preferred, however alternative equations may be utilized to determine eligiblity if deemed acceptable by the Investigator and Medical Monitor).
Are the trial subjects under 18? yes
Number of subjects for this age range: 260
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) Subjects receiving invasive endotracheal mechanical ventilation
4) 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).
5) 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 (under appropriate conditions, e.g. not hemolyzed)is allowed for eligibility determination.
6) 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
7) Clinically significant abnormal ECG findings, as judged by the Investigator or qualified designee
8) Subjects anticipated to be discharged from the hospital in < 24 hours from the time of randomization
9) Exclusionary medications include:
a. Herbal supplements which have evidence of adversely affecting absorption and clearance mechanisms (e.g., strong inhibitors of OAT3) within 21 days prior to randomization
b. The following prescription medications:
? Use of systemic medications (either chronically (i.e., >14 days
for neonates and infants <2 months old, or >28 days for
subjects =2-=12 months of age) 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. The only exception is systemic corticosteroids will be acceptable if they are not taken chronically for a non-RSV-related indication.
? 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.
? Prescription medications which are known to be strong
inhibitors of the OAT3 transporter, within 21 days prior to
randomization
c. Investigational drug trial medications within 30 days or 5 half-lives (whichever is longer) prior to randomization


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Respiratory Syncytial Virus (RSV) Infection
MedDRA version: 20.0 Level: PT Classification code 10061603 Term: Respiratory syncytial virus infection System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: ALS-008176
Product Code: ALS-008176
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: N/A
CAS Number: Pending
Current Sponsor code: ALS-008176
Other descriptive name: ALS-008176
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Product Name: ALS-008176
Product Code: ALS-008176
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: N/A
CAS Number: Pending
Current Sponsor code: ALS-008176
Other descriptive name: ALS-008176
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: SAD: Post randomisation, Study days 2 to 6 and Completion visit day 7
MAD: Post randomisation, Study days 2 to 10, Outpatient safety visit and Completion day 11.

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)

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
• To evaluate the antiviral activity of ALS-008176 after single and multiple doses of ALS-008176
• To determine if ALS-008176 exposure results in the emergence of resistant strains of RSV

Main Objective: To evaluate the safety and tolerability of single and multiple doses of ALS-008176

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: SAD: Post randomisation, Study days 2 to 6 and Completion visit day 7
MAD: Post randomisation, Study days 2 to 10, Outpatient safety visit and Completion day 11.

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, AUC0-24h, AUC0-inf or AUC0-last
PK parameters of ALS-008112 and ALS-008144 (and other metabolites as applicable) in blood following repeat dose administration: Cmax, Cmin, tmax, t1/2, AUC0-12h, AUC0-24h, AUC0-tau, AUC0-inf or AUC0-last
RSV viral RNA concentrations in nasal swabs or aspirates as measured by quantitative RT-PCR
Changes in the RSV polymerase that result in reduced sensitivity to ALS-008112

Secondary ID(s)

ALS-8176-503

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 01/12/2018
• Date Completed: 15/02/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005104-33/results