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This randomized, double-blind, placebo-controlled, 4 part study will assess the safety, tolerability, pharmacokinetics and antiviral activity of orally administered AL-794 in healthy volunteers (HV).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AL-794 | Experimental | AL-794 administered orally in a suspension |
|
| Vehicle | Placebo Comparator | Suspension vehicle alone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AL-794 | Drug |
| ||
| Placebo/Vehicle |
| Measure | Description | Time Frame |
|---|---|---|
| Safety Data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results | Safety data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results (including chemistry, hematology, and urinalysis). Note that in the Multiple Ascending Dose (MAD) portion of the study, the time frame is from Screening to Day 17 (MAD) and for the Viral Challenge portion of the study the time frame is from Screening to Day 28 (Viral Challenge). | Screening to Day 8 in Single Dose and Food Effect portions of the study |
| Safety Data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results | Safety data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results (including chemistry, hematology, and urinalysis). | Screening to Day 17 in the Multiple Ascending Dose portion of the study |
| Safety Data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results | Safety data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results (including chemistry, hematology, and urinalysis). | Screening to Day 28 in the Viral Challenge portion of the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: AL-794 | Pharmacokinetic parameter of ALS-033719 and ALS-033927 (and other metabolites, if applicable) in plasma following single dose administration | From baseline to Day 8 for Single Dose and Food Effect cohorts |
| Cmax: AL-794 |
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Inclusion Criteria:
Exclusion Criteria:
Clinically significant cardiovascular, respiratory, renal, gastrointestinal, hepatic, hematologic, neurologic, thyroid or any other medical illness or psychiatric disorder, as determined by the Investigator, and/or Sponsor's Medical Monitor.
Positive screening test for hepatitis A, B, C or HIV infection.
Clinically significant laboratory abnormalities or abnormalities which are deemed to interfere with the ability to interpret study data.
Creatinine clearance of less than 60 mL/min (Cockroft Gault).
Total bilirubin, ALT, AST, or Alkaline Phosphatase > 1.2 X ULN.
Any condition that, in the opinion of the investigator, would compromise the study's objectives or the well-being of the subject or prevent the subject from meeting the study requirements.
Participation in an investigational drug trial or having received an investigational vaccine within 3 months prior to study medication (or inoculation for Part 4 subjects).
Clinically significant abnormal ECG findings.
Clinically significant blood loss or elective blood donation of significant volume (i.e., > 500 mL) within 90 days of first dose of study drug
Heart rate, respiratory rate, temperature or blood pressure values outside of the normal range, per local standards.
Unwilling to abstain from alcohol for 1 week before the start of admission until the final Completion Visit assessments.
History of regular alcohol intake > 14 units per week of alcohol for females and > 21 units per week for males (one unit is defined as 8 g alcohol) within 3 months of admission.
For Parts 1-3, subjects with a history of tobacco use or use of nicotine-containing products within 2 weeks of the screening visit. For Part 4, subjects who have a significant history of any tobacco use at any time.
The subject has a positive pre-study drug screen.
The use of concomitant medications, including prescription, over the counter medications, herbal medications, inducers or inhibitors of CYP450 enzymes or drug transporters (including P-gp), within 14 days prior to the first dose of study medication, unless approved by the Sponsor's Medical Monitor. Occasional use of ibuprofen or acetaminophen is permitted.
Exposure to more than four new investigational entities within 12 months prior to the first dosing day (Parts 1-3) or inoculation (Part 4).
Evidence of active infection, including respiratory tract infection within 2 weeks prior to admission.
Pregnant or nursing females, or women of childbearing potential. Men whose female partners are pregnant or contemplating pregnancy from the date of screening until 90 days after end of study.
Hypersensitivity to the active substances or to any of the excipients of AL-794.
Unwillingness or inability to comply with the study protocol for any other reason.
Part 4 ONLY: Contraindications to challenge with influenza virus or procedures related or influenza challenge study. For example:
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| Name | Affiliation | Role |
|---|---|---|
| Malcolm Boyce | HMR | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hammersmith Medicines Research Ltd (HMR) | London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30053042 | Derived | Yogaratnam J, Rito J, Kakuda TN, Fennema H, Gupta K, Jekle CA, Mitchell T, Boyce M, Sahgal O, Balaratnam G, Chanda S, Van Remoortere P, Symons JA, Fry J. Antiviral Activity, Safety, and Pharmacokinetics of AL-794, a Novel Oral Influenza Endonuclease Inhibitor: Results of an Influenza Human Challenge Study. J Infect Dis. 2019 Jan 7;219(2):177-185. doi: 10.1093/infdis/jiy410. | |
| 29927386 |
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Suspension vehicle without active drug |
|
Pharmacokinetic parameter of ALS-033719 and ALS-033927 (and other metabolites, if applicable) in plasma following multiple dose administration
| From baseline to Day 17 for Multiple Ascending Dose Cohorts |
| AUC: AL-794 | Pharmacokinetic parameter of ALS-033719 and ALS-033927 (and other metabolites, if applicable) in plasma following single dose administration | From baseline to Day 8 for Single Dose and Food Effect cohorts |
| AUC: AL-794 | Pharmacokinetic parameter of ALS-033719 and ALS-033927 (and other metabolites, if applicable) in plasma following multiple dose administration | From baseline to Day 17 for Multiple Ascending Dose cohorts |
| CMax: Fed vs. Fasted | Comparison of Cmax after a single oral dose in HV in fasted conditions as compared with fed conditions. | First dose to Day 8 (Single Ascending Dose/Food Effect) |
| AUC: Fed vs. Fasted | Comparison of AUC after a single oral dose in HV in fasted conditions as compared with fed conditions. | First dose to Day 8 (Single Ascending Dose/Food Effect) |
| Influenza Viral Load | AUC0-t of influenza viral load, as determined by quantitative polymerase chain reaction (PCR) assay of nasopharyngeal swab, from baseline (i.e., immediately prior to treatment onset) through checkout, Day 17, and completion of study | Baseline to Day 28 |
| Peak influenza viral load after treatment | Peak influenza viral load after treatment onset, as determined by quantitative PCR assay of nasopharyngeal swab | inoculation to Day 28 |
| Derived |
| Kakuda TN, Yogaratnam J, Rito J, Boyce M, Mitchell T, Gupta K, Symons JA, Chanda S, Van Remoortere P, Fry J. Phase I study on safety and pharmacokinetics of a novel influenza endonuclease inhibitor, AL-794 (JNJ-64155806), following single- and multiple-ascending doses in healthy adults. Antivir Ther. 2018;23(7):555-566. doi: 10.3851/IMP3244. Epub 2018 Jun 21. |
| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C038978 | sfericase |
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