Alios ALS-008176 (RSV)

Principal Investigator: Kwabena Ampofo
Keywords: Respiratory , Synctial , Virus , RSV Department: Pediatric Administration
IRB Number: 00085403 Co Investigator:  
Specialty: Pediatric Pulmonary Care, Pediatric Infectious Diseases
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Zachary Mitchell
zachary.mitchell@hsc.utah.edu
801-587-7467

Brief Summary

STUDY PURPOSE
 
This study is being performed to determine preliminary safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) data after single and multiple doses of ALS-008176 given to infants ≥ 1.0 to ≤ 12.0 months of age who are hospitalized with RSV infection. Our site is only participating in the multiple dose portion of the study. 
 
STUDY OBJECTIVES
 
Primary Objective
To evaluate the safety and tolerability of single and multiple doses of ALS-008176
 
Secondary Objectives
  • 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
Exploratory Objectives
  • To evaluate the impact of ALS-008176 on the clinical course of RSV infection
  • To evaluate the relationship between viral kinetics and clinical outcomes
  • To evaluate the impact of ALS-008176 on biomarkers potentially associated with the inflammatory response induced by acute RSV infection
  • To evaluate the PK of ALS-008112 and ALS-008144 (and other metabolites, if applicable) in nasal swabs following multiple doses of ALS-008176, if an acceptable testing methodology can be established

Inclusion Criteria

INCLUSION CRITERIA
Subjects must meet all of the following criteria to be included in the study:
 
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 infection is permissible.
  • has been hospitalized for < 96 hours (at 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 eligibility if deemed acceptable by the Investigator and Medical Monitor)

Exclusion Criteria

EXCLUSION CRITERIA
Subjects will be ineligible for this study if they meet any one of the following 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 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
 
8) Subjects anticipated to be discharged from the hospital in < 24 hours from the time of randomization
 
9) Exclusionary medications include:
  • Herbal supplements which have evidence of adversely affecting absorption and clearance mechanisms (e.g., strong inhibitors of OAT3) within 21 days prior to randomization
 
  • The following prescription medications:
 
a) 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.
 
b) 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.
 
c) Prescription medications which are known to be a strong inhibitors of the OAT3 transporter, within 21 days prior to randomization (See Prohibited Medications. Section 5.8)
 
  • 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
 
10) Infants who are breastfeeding and their mother is taking any of the exclusionary medications described in exclusion criterion 9.
 
11) Infants with another child in the household who has enrolled in the study
 
12) Infants with known fructose intolerance (due to sorbitol in study medication)