A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the<br>Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered ALS-008176 Regimens in Adult Subjects Hospitalized with Respiratory Syncytial Virus
- Conditions
- Respiratory Syncytial Virus Infection (RSV)10024970viral infection10047438
- Registration Number
- NL-OMON47223
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
1. Men or women *18 years of age or the legal age of consent in the jurisdiction in
which the study is taking place, defined at the time of randomization.;2. Hospitalized (or in emergency room prior to hospitalization) at the time of randomization and unlikely to be discharged for the first 24 hours after randomization. ;3. Diagnosed with RSV infection based on PCR-based assay with or without co-infection with another respiratory pathogen (eg, influenza,human metapneumovirus, or bacteria).
NOTE: in cases where commercial PCR-based assays are not available at the site, the sponsor should be consulted for agreement on the assay to be used. ;4. Has an acute respiratory illness with signs and symptoms consistent with a viral infection (eg, fever, cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, shortness of breath, or wheezing) with onset *5 days from the anticipated time of randomization.;NOTE: The viral infection may present in any way as long as the underlying precipitant of the illness is considered by the investigator to be due to RSV infection. Examples of such an illness include:
* An upper or lower viral respiratory tract infection (eg, *flu-like illness*)
* Pneumonia
* Respiratory distress
* Asthma exacerbation
* Chronic obstructive pulmonary disease (COPD) exacerbation;5. With the exception of the RSV disease, medically stable on the basis of medical history, physical examination, vital signs, and 12-lead ECG performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population and/or the RSV infection. This determination must be recorded in the subject*s source documents and initialed by the investigator.;6. Medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal do not pose an unacceptable risk to the subject, are not clinically significant, or are appropriate and reasonable for the population under study. This determination must be recorded in the subject*s source documents and initialed by the investigator. A single repeat laboratory evaluation is allowed for eligibility determination.;7. Must sign an ICF (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.;8. A woman must have a negative urine ß-human chorionic gonadotropin at screening.;9. Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. ;Before randomization, a woman must be either:
a. Not of childbearing potential defined as:
* Postmenopausal: a postmenopausal state is defined as >45 years and no menses for 12 consecutive months without an alternative medical cause, OR
* Permanently sterile: permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy.;b. Of childbearing potential and, if heterosexually active,
* Practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly)
Examples
1. Subjects who are not expected to survive for more than 48 hours.;2. Subjects who have had major thoracic or abdominal surgery in the 6 weeks prior to
randomization.;3. Subjects who are considered by the investigator to be immunocompromised within the past 12 months, whether due to underlying medical condition (eg, malignancy or genetic disorder) or medical therapy (eg, medications other than corticosteroids for the treatment of COPD or asthma exacerbations,, chemotherapy, radiation, stem cell or solid organ transplant).;4. Subjects with a known history of human immunodeficiency virus (HIV) or chronic viral hepatitis.;5. Subjects with ALT *3 times the upper limit of normal (ULN) AND bilirubin *2×ULN (direct >35%) OR ALT *5×ULN at screening. ;6. Subjects undergoing peritoneal dialysis, hemodialysis, or hemofiltration or with an estimated glomerular filtration rate (GFR, determined by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) of <60 mL/min.
GFR= 140 * min (Scr/k,1)* * max (Scr/k,1)-1.209 * 0.993Age * sex * race
Legend:
Min minimum of Scr/* or 1
Max maximum of Scr/* or 1
Scr serum creatinine measured in mg/dL
* 0.7 for women, 0.9 for men
* -0.329 for women, -0.411 for men
Age measured in years
Sex 1.018 for women, 1 for men
Race 1.159 for black, 1 for white and other;NOTE: The IDMC may recommend to lower the exclusionary GFR limit to <30 or <15 mL/min/1.73m2 if any available emerging PK data in subjects with GFR *60 mL/min/1.73m2 suggest that ALS-008112 exposure in the setting of moderate (ie, GFR *30 to <60 mL/min/1.73m2) or severe (ie, GFR *15 to <30 mL/min) renal impairment are projected to remain within an acceptable range.;In the event a local site is unable to perform a CKD-EPI determination, an alternative methodology for determining GFR is permissible if discussed with and approved by the sponsor.;7. Known allergies, hypersensitivity, or intolerance to lumicitabine/ALS-008176 or its excipients (refer to the IB).;8. Subjects unwilling to undergo mid-turbinate nasal swab procedures or with any physical abnormality which limits the ability to collect regular nasal specimens.;9. Subjects unable to take medications enterally or with a known gastrointestinal-related condition that is considered by the sponsor or investigator to be likely to interfere with study drug absorption.;10. Women who are pregnant or breastfeeding.;11. Men who plan to father a child while enrolled in this study or within 104 days after the last dose of study drug.;12. Subjects taking any disallowed therapies as noted in Section 8 before the planned first dose of study drug.;13. Subjects who received prescription medications intended to prevent or treat the RSV infection itself (eg, ribavirin, IV immunoglobulin, palivizumab), an investigational drug, an investigational vaccine, or used an invasive investigational medical device within 30 days or 5 half-lives (whichever is longer) before the planned first dose of study drug or is currently enrolled in an investigational study.;14. Subjects with any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.;15. Subjects who have used systemic corticosteroids for >7 consecutive days immediately prior to randomization at doses higher than 20 mg/day of prednisone or e
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>For Part 1:<br /><br>The primary endpoint is the PK of ALS-008112 and ALS-008144 (and other<br /><br>metabolites, if applicable) in plasma.<br /><br>For Part 2:<br /><br>The primary endpoint is RSV RNA viral load (measured by qRT-PCR in the<br /><br>mid-turbinate nasal swab specimens) area under the curve (AUC) from immediately<br /><br>prior to first dose of study drug (baseline) until Day 7.</p><br>
- Secondary Outcome Measures
Name Time Method