Clinical Trials List
Protocol Number64041575RSV2003
NCT Number(ClinicalTrials.gov Identfier)NCT02935673
2016-10-21 - 2018-11-19
Phase II
Terminated6
ICD-10B97.4
Respiratory syncytial virus as the cause of diseases classified elsewhere
ICD-9079.6
Respiratory syncytial virus(RSV) infections in conditions classified elsewhere and of unspecified site
A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered ALS-008176 Regimens in Adult Subjects Hospitalized with Respiratory Syncytial Virus
-
Trial Applicant
Johnson & Johnson
-
Sponsor
JOHNSON & JOHNSON TAIWAN LTD.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 王秉槐 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 湯宏仁 Division of Infectious Disease
- Wei-Ting Chang Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Tzu-Tao Chen Division of Thoracic Medicine
- Chih-Cheng Chang Division of Thoracic Medicine
- Po-Hao Feng Division of Thoracic Medicine
- Kuan-Yuan Chen Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
40 Stop recruiting
Audit
CRO
Co-Principal Investigator
- Fu-Lun Chen Division of Infectious Disease
- Tsong-Yih Ou Division of Infectious Disease
- Chih-Hsin Lee Division of Thoracic Medicine
- Shian-Jiun Lin Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Jann-Tay Wang Division of Infectious Disease
- 陳世英 Division of Infectious Disease
- 李麗娜 Division of Infectious Disease
- Chong-Jen Yu Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Respiratory Syncytial Virus (RSV)
Objectives
Primary Objectives
For Part 1:
The primary objective is to characterize the pharmacokinetics (PK) and to confirm the population PK
(popPK) model derived from healthy volunteers in hospitalized adults who are infected with RSV.
For Part 2:
The primary objective is to determine in hospitalized adults who are infected with RSV the dose-response
relationship of multiple regimens of ALS-008176 on antiviral activity based on nasal RSV shedding using
quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay.
Secondary Objectives
The secondary objectives for Part 1 and Part 2 are to determine in hospitalized adults who are infected
with RSV:
The safety and tolerability of ALS-008176.
The impact of ALS-008176 on the clinical course of RSV infection including:
Duration of hospital stay.
Duration of supplemental oxygen.
Evolution of Activities of Daily Living (ADL) as assessed by Katz ADL score.
Time to clinical stability.
Improvement on the ordinal scale.
Rate of mortality and complications.
The antiviral activity based on nasal RSV shedding using qRT-PCR assay (secondary for Part 1
only) and the time to cessation of nasal RSV shedding.
The impact of ALS-008176 on the emergence of resistant strains of RSV.
The PK of ALS-008112 and ALS-008144 (and other metabolites, if applicable) in plasma.
The relationship between the PK and pharmacodynamics (PD; antiviral activity, clinical symptoms,
and selected safety parameters) after single (loading dose [LD]) and repeated oral dosing
(maintenance dose [MD]) of ALS-008176.
Test Drug
ALS-008176 (JNJ-64041575)
Active Ingredient
ALS-008176 (JNJ-64041575)
Dosage Form
tablets
Dosage
250 or 500 mg
Endpoints
Primary Endpoints
For Part 1:
The primary endpoint is the PK of ALS-008112 and ALS-008144 (and other metabolites, if applicable) in
plasma.
For Part 2:
The primary endpoint is RSV RNA viral load (measured by qRT-PCR in the mid-turbinate nasal swab
specimens) area under the curve (AUC) from immediately prior to first dose of study drug (baseline) until
Day 7.
Secondary Endpoints
The secondary endpoints for Part 1 and Part 2 are:
Safety/tolerability including adverse events (AEs), physical examinations, vital signs,
electrocardiograms (ECGs), and clinical laboratory results.
RSV clinical course endpoints:
Length of hospital stay from admission to discharge and from study treatment initiation to
discharge.
Length of hospital stay from admission to readiness for discharge and from study treatment
initiation to readiness for discharge, with readiness for discharge defined by the investigator.
Need for and duration of intensive care unit (ICU) stay.
Need for and duration of supplemental oxygen (regardless of method used).
Number of hours until peripheral capillary oxygen saturation (SpO2) ≥93% on room air among
subjects who were not on supplemental oxygen prior to the onset of respiratory symptoms.
Respiratory rate, SpO2, and body temperature return to pre-RSV disease level.
Need for and duration of noninvasive ventilator support (eg, continuous positive airway
pressure) and/or invasive ventilator support (eg, endotracheal-mechanical ventilation or
mechanical ventilation via tracheostomy).
Time to return to pre-RSV functional status (Katz ADL score).
Need for hydration and feeding by intravenous (IV) catheter/nasogastric tube.
Time to clinical stability defined as the time at which the following criteria are all met:
o normalization of blood oxygen level (return to baseline; by pulse oximetry) without
requirement of supplemental oxygen beyond baseline level
o normalization of oral feeding
o normalization of respiratory rate
o normalization of heart rate
Improvement on the ordinal scale.
All-cause mortality.
RSV RNA viral load as measured by qRT-PCR of the mid-turbinate nasal swab specimens which
will be used to determine the following:
Viral load over time.
Peak viral load, time to peak viral load, rate of decline of viral load, and time to RSV RNA
being undetectable.
Proportion of subjects with undetectable viral load at each time point.
The RSV RNA viral load AUC from immediately prior to first dose of study drug (baseline)
until Day 7 (secondary for Part 1 only).
RSV RNA viral load AUC from immediately prior to first dose of study drug (baseline) until
Day 10 and until Day 14.
RSV RNA viral load AUC in subjects assigned to a longer dosing duration, if dosing duration is
increased by the Independent Data Monitoring Committee (IDMC), from baseline until 1 day
after the last dose of study drug (Part 2 only).
Sequence changes (postbaseline) in the RSV polymerase L-gene and other regions (only if no
mutations are seen in the L-gene) of the RSV genome compared with baseline sequences.
Population-derived PK parameters of ALS-008112.
For Part 1:
The primary endpoint is the PK of ALS-008112 and ALS-008144 (and other metabolites, if applicable) in
plasma.
For Part 2:
The primary endpoint is RSV RNA viral load (measured by qRT-PCR in the mid-turbinate nasal swab
specimens) area under the curve (AUC) from immediately prior to first dose of study drug (baseline) until
Day 7.
Secondary Endpoints
The secondary endpoints for Part 1 and Part 2 are:
Safety/tolerability including adverse events (AEs), physical examinations, vital signs,
electrocardiograms (ECGs), and clinical laboratory results.
RSV clinical course endpoints:
Length of hospital stay from admission to discharge and from study treatment initiation to
discharge.
Length of hospital stay from admission to readiness for discharge and from study treatment
initiation to readiness for discharge, with readiness for discharge defined by the investigator.
Need for and duration of intensive care unit (ICU) stay.
Need for and duration of supplemental oxygen (regardless of method used).
Number of hours until peripheral capillary oxygen saturation (SpO2) ≥93% on room air among
subjects who were not on supplemental oxygen prior to the onset of respiratory symptoms.
Respiratory rate, SpO2, and body temperature return to pre-RSV disease level.
Need for and duration of noninvasive ventilator support (eg, continuous positive airway
pressure) and/or invasive ventilator support (eg, endotracheal-mechanical ventilation or
mechanical ventilation via tracheostomy).
Time to return to pre-RSV functional status (Katz ADL score).
Need for hydration and feeding by intravenous (IV) catheter/nasogastric tube.
Time to clinical stability defined as the time at which the following criteria are all met:
o normalization of blood oxygen level (return to baseline; by pulse oximetry) without
requirement of supplemental oxygen beyond baseline level
o normalization of oral feeding
o normalization of respiratory rate
o normalization of heart rate
Improvement on the ordinal scale.
All-cause mortality.
RSV RNA viral load as measured by qRT-PCR of the mid-turbinate nasal swab specimens which
will be used to determine the following:
Viral load over time.
Peak viral load, time to peak viral load, rate of decline of viral load, and time to RSV RNA
being undetectable.
Proportion of subjects with undetectable viral load at each time point.
The RSV RNA viral load AUC from immediately prior to first dose of study drug (baseline)
until Day 7 (secondary for Part 1 only).
RSV RNA viral load AUC from immediately prior to first dose of study drug (baseline) until
Day 10 and until Day 14.
RSV RNA viral load AUC in subjects assigned to a longer dosing duration, if dosing duration is
increased by the Independent Data Monitoring Committee (IDMC), from baseline until 1 day
after the last dose of study drug (Part 2 only).
Sequence changes (postbaseline) in the RSV polymerase L-gene and other regions (only if no
mutations are seen in the L-gene) of the RSV genome compared with baseline sequences.
Population-derived PK parameters of ALS-008112.
Inclution Criteria
1. Criterion modified per Amendment 2:
1.1. Criterion modified per Amendment 3:
1.2 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. Criterion modified per Amendment 2:
3.1. 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. Criterion modified per Amendment 2:
4.1. 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. Criterion modified per Amendment 2:
5.1. 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. Criterion modified per Amendment 2:
8.1. A woman must have a negative urine -human chorionic gonadotropin at
screening.
9. Criterion modified per Amendment 2:
9.1. 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:
o Postmenopausal: a postmenopausal state is defined as >45 years and no menses for 12 consecutive months without an alternative medical cause,OR
o 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,
o Practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly)
Examples of highly effective contraceptives include
- User-independent methods:
implantable progestogen-only hormone contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject.)
- User-dependent methods:
combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, and transdermal; progestogen-only hormone contraception associated with inhibition of ovulation: oral and injectable
Typical use failure rates may differ from those when used consistently and correctly.
o Agrees to remain on a highly effective method throughout the study and for at least 44 days after the last dose of study drug.
Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes (eg, a woman who is not heterosexually active becomes active) a woman must begin a highly effective method of contraception, as described throughout the inclusion criteria.
10. Criterion modified per Amendment 2:
10.1. Contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies.
During the study and until the end of relevant systemic exposure, plus a minimum of 1 spermatogenesis cycle (ie, 104 days in total) after receiving the last dose of study drug, a man:
• Who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (eg, condom with spermicidal foam/gel/film/cream/suppository)
• Who is sexually active with a pregnant woman must use a condom
• Must agree not to donate sperm
11. Criterion modified per Amendment 2:
11.1. Female partners of men must either be surgically sterilized, postmenopausal
(amenorrhea for a minimum of 1 year) or, if of childbearing potential, must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) during the study and for 104 days following the last dose of study drug.
12. Criterion modified per Amendment 2:
12.1. A woman must agree not to donate eggs (ova, oocytes) during the study and for at least 44 days after receiving the last dose of study drug.
13. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
14. Subject must have a body weight 50.0 kg, at screening.
1.1. Criterion modified per Amendment 3:
1.2 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. Criterion modified per Amendment 2:
3.1. 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. Criterion modified per Amendment 2:
4.1. 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. Criterion modified per Amendment 2:
5.1. 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. Criterion modified per Amendment 2:
8.1. A woman must have a negative urine -human chorionic gonadotropin at
screening.
9. Criterion modified per Amendment 2:
9.1. 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:
o Postmenopausal: a postmenopausal state is defined as >45 years and no menses for 12 consecutive months without an alternative medical cause,OR
o 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,
o Practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly)
Examples of highly effective contraceptives include
- User-independent methods:
implantable progestogen-only hormone contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject.)
- User-dependent methods:
combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, and transdermal; progestogen-only hormone contraception associated with inhibition of ovulation: oral and injectable
Typical use failure rates may differ from those when used consistently and correctly.
o Agrees to remain on a highly effective method throughout the study and for at least 44 days after the last dose of study drug.
Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes (eg, a woman who is not heterosexually active becomes active) a woman must begin a highly effective method of contraception, as described throughout the inclusion criteria.
10. Criterion modified per Amendment 2:
10.1. Contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies.
During the study and until the end of relevant systemic exposure, plus a minimum of 1 spermatogenesis cycle (ie, 104 days in total) after receiving the last dose of study drug, a man:
• Who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (eg, condom with spermicidal foam/gel/film/cream/suppository)
• Who is sexually active with a pregnant woman must use a condom
• Must agree not to donate sperm
11. Criterion modified per Amendment 2:
11.1. Female partners of men must either be surgically sterilized, postmenopausal
(amenorrhea for a minimum of 1 year) or, if of childbearing potential, must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) during the study and for 104 days following the last dose of study drug.
12. Criterion modified per Amendment 2:
12.1. A woman must agree not to donate eggs (ova, oocytes) during the study and for at least 44 days after receiving the last dose of study drug.
13. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
14. Subject must have a body weight 50.0 kg, at screening.
Exclusion Criteria
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. Criterion modified per Amendment 2:
3.1. 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. Criterion modified per Amendment 2:
6.1. Subjects undergoing peritoneal dialysis, hemodialysis, or hemofiltration or with an estimated glomerular filtration rate (GFR, determined by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation15) of <60 mL/min/1.73m2.
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/1.73m2) 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 ALS-008176 or its excipients (refer to the IB).5
8. Criterion deleted per Amendment 2
9. Subjects unwilling to undergo mid-turbinate nasal swab procedures or with any physical abnormality which limits the ability to collect regular nasal specimens.
10. 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.
11. Women who are pregnant or breastfeeding.
12. Criterion modified per Amendment 2:
12.1. Men who plan to father a child while enrolled in this study or within 104 days after the last dose of study drug.
13. Subjects taking any disallowed therapies as noted in Section 8 before the planned first dose of study drug.
14. Criterion modified per Amendment 2:
14.1. 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.
15. 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.
16. Subjects who have used systemic corticosteroids for >7 consecutive days immediately prior to randomization at doses higher than 20 mg/day of prednisone or equivalent.
17. Subject is being treated with extracorporeal membrane oxygenation.
18. Subjects with 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table (see Attachment 1):
Hemoglobin <9.5 g/dL
Platelet count <75,000/mm3
White blood cell count <1,000/mm³
Absolute neutrophil count <1,000/mm³
Note: Retesting of abnormal laboratory values that may lead to exclusion will be allowed once without asking prior approval from the sponsor. Retesting will be performed once within the screening window. Subjects with a normal value at retest may be included.
2. Subjects who have had major thoracic or abdominal surgery in the 6 weeks prior to randomization.
3. Criterion modified per Amendment 2:
3.1. 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. Criterion modified per Amendment 2:
6.1. Subjects undergoing peritoneal dialysis, hemodialysis, or hemofiltration or with an estimated glomerular filtration rate (GFR, determined by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation15) of <60 mL/min/1.73m2.
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/1.73m2) 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 ALS-008176 or its excipients (refer to the IB).5
8. Criterion deleted per Amendment 2
9. Subjects unwilling to undergo mid-turbinate nasal swab procedures or with any physical abnormality which limits the ability to collect regular nasal specimens.
10. 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.
11. Women who are pregnant or breastfeeding.
12. Criterion modified per Amendment 2:
12.1. Men who plan to father a child while enrolled in this study or within 104 days after the last dose of study drug.
13. Subjects taking any disallowed therapies as noted in Section 8 before the planned first dose of study drug.
14. Criterion modified per Amendment 2:
14.1. 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.
15. 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.
16. Subjects who have used systemic corticosteroids for >7 consecutive days immediately prior to randomization at doses higher than 20 mg/day of prednisone or equivalent.
17. Subject is being treated with extracorporeal membrane oxygenation.
18. Subjects with 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table (see Attachment 1):
Hemoglobin <9.5 g/dL
Platelet count <75,000/mm3
White blood cell count <1,000/mm³
Absolute neutrophil count <1,000/mm³
Note: Retesting of abnormal laboratory values that may lead to exclusion will be allowed once without asking prior approval from the sponsor. Retesting will be performed once within the screening window. Subjects with a normal value at retest may be included.
The Estimated Number of Participants
-
Taiwan
6 participants
-
Global
216 participants
