A Study of AL-794 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses, and the Antiviral Activity of Multiple Doses in an Influenza Challenge Study

NCT02588521 | Completed Phase 1

• 1 other identifier: AL-794-801
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Influenza

Outcome Measures

Primary Outcomes (3)

• 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.

Secondary Outcomes (8)

• Cmax: AL-794

  From baseline to Day 8 for Single Dose and Food Effect cohorts

• Cmax: AL-794

  From baseline to Day 17 for Multiple Ascending Dose Cohorts

• AUC: AL-794

  From baseline to Day 8 for Single Dose and Food Effect cohorts

• AUC: AL-794

  From baseline to Day 17 for Multiple Ascending Dose cohorts

• CMax: Fed vs. Fasted

  First dose to Day 8 (Single Ascending Dose/Food Effect)

Study Arms (2)

AL-794

EXPERIMENTAL

AL-794 administered orally in a suspension

Drug: AL-794

Vehicle

PLACEBO COMPARATOR

Suspension vehicle alone

Other: Placebo/Vehicle

Interventions

AL-794 DRUG

AL-794

Placebo/Vehicle OTHER

Suspension vehicle without active drug

Vehicle

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has provided written consent.
• In the investigator's opinion, the subject is able to understand and comply with protocol requirements, instructions, and protocol stated restrictions and is likely to complete the study as planned.
• Subject is in good health as deemed by the investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests and ECG.
• Male or female, 18-60 years of age (Parts 1-3). For Part 4, Males or female, 18-55 years of age.
• Body mass index (BMI) 18-30kg/m2, inclusive. The minimum weight is 50 kg.
• A female subject is eligible to participate in this study if she is of non childbearing potential or postmenopausal and not receiving hormone replacement therapy.
• If male, subject is surgically sterile or practicing specific forms of birth control until 90 days after the end of the study.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alios Biopharma Inc.: lead

Study Sites (1)

Hammersmith Medicines Research Ltd (HMR)

London, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 30053042 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.

  PMID: 29927386 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

sfericase

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Malcolm Boyce

  HMR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2015
• First Posted: October 28, 2015
• Study Start: August 31, 2015
• Primary Completion: August 14, 2017
• Study Completion: August 14, 2017
• Last Updated: October 11, 2017

Record last verified: 2017-10

Locations

GB (1)