InfluenzaPhase 1NCT02588521
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
A Phase 1 study testing AL-794 in people with Influenza, run by Alios Biopharma Inc. at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- AL-794
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 Aug 2015to 14 Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 38Show fewer
- 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:
- Subject is not sero-suitable.
- Immunocompromised status or diagnosis of active autoimmune disease.
- Known allergy to constituents of challenge virus.
- History of severe illness during adulthood due to a respiratory virus.
- Inability to tolerate repeated nasopharyngeal swabs.
- Abnormal pulmonary function in the opinion of the Investigator, as evidenced by the responses to the respiratory screening questions and /or clinically significant abnormalities in spirometry.
- Significant history of asthma.
- Any significant abnormality altering the anatomy of the nose or nasopharynx.
- Any clinically significant history of epistaxis.
- Any nasal or sinus surgery within six months of inoculation.
- Health care workers who are reasonably likely to come into contact with severely immuno-compromised patients
- Presence of household member or close contact who has known immunodeficiency, is receiving immunosuppressant medication, is undergoing or soon to undergo cancer chemotherapy, has been diagnosed with emphysema, COPD, or other severe lung disease, has received a bone marrow or solid organ transplant, resides in a nursing home
- Evidence of vaccinations within the four weeks prior to inoculation/dosing, whichever occurs first.
- Intention to receive any vaccination(s) before the Day 28 Follow Up Visit
- Prior participation in another Human Viral Challenge Study in the preceding 12 months taken from the date of inoculation in the previous study to the date of expected inoculation in this study.
- Receipt of systemic glucocorticoids or systemic antiviral drugs within six months prior to inoculation/dosing.
- Receipt of any systemic chemotherapy agent, immunoglobulins or any other cytotoxic or immunosuppressive drugs at any time.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, First-in-human, Study of Orally Administered AL-794 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses, and the Antiviral Activity of Multiple Doses in an Influenza Challenge Study in Healthy Subjects
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
- Being tested
- AL-794, Placebo/Vehicle
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AL-794Drug
Placebo/VehicleOther
Suspension vehicle without active drug
| Study group | Role | What they receive |
|---|---|---|
| AL-794 | Experimental | AL-794 administered orally in a suspension Receives: Drug: AL-794 |
| Vehicle | Placebo comparator | Suspension vehicle alone Receives: Other: Placebo/Vehicle |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: Screening to Day 28 in the Viral Challenge portion of the study.
Secondary outcomes (8)
Cmax: AL-794
Pharmacokinetic parameter of ALS-033719 and ALS-033927 (and other metabolites, if applicable) in plasma following single dose administration
Measured: From baseline to Day 8 for Single Dose and Food Effect cohorts
Cmax: AL-794
Pharmacokinetic parameter of ALS-033719 and ALS-033927 (and other metabolites, if applicable) in plasma following multiple dose administration
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: inoculation to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2015 (estimated)
- Study start31 Aug 2015
- Primary completion14 Aug 2017
- Study completion14 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alios Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Malcolm Boyce, Principal investigator, HMR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02588521
- Sponsor's protocol ID
- AL-794-801
- Status last verified
- Oct 2017
- First submitted
- 14 Oct 2015
- Last updated
- 11 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated device
- No
Publications
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.
PubMed 30053042Kakuda 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.
PubMed 29927386
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, First-in-human, Study of Orally Administered AL-794 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses, and the Antiviral Activity of Multiple Doses in an Influenza Challenge Study in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02588521
- Acronym / sponsor ID
- AL-794-801
- Conditions
- Influenza
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- Alios Biopharma Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Aug 2015 (actual)
- Primary completion
- 14 Aug 2017 (actual)
- Study completion
- 14 Aug 2017 (actual)
- First posted
- 28 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AL-794 | Experimental | Drug: AL-794AL-794 administered orally in a suspension |
| Vehicle | Placebo comparator | Other: Placebo/VehicleSuspension vehicle alone |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (38 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AL-794 | Drug | AL-794 |
| Placebo/VehicleSuspension vehicle without active drug | Other | Vehicle |
Primary outcome
Safety Data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results
Time frame: 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 (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).
Safety Data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results
Time frame: 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 (including chemistry, hematology, and urinalysis).
Safety Data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results
Time frame: Screening to Day 28 in the Viral Challenge 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 (including chemistry, hematology, and urinalysis).
8 secondary outcomes
Cmax: AL-794
Time frame: From baseline to Day 8 for Single Dose and Food Effect cohorts
Cmax: AL-794
Time frame: From baseline to Day 17 for Multiple Ascending Dose Cohorts
AUC: AL-794
Time frame: From baseline to Day 8 for Single Dose and Food Effect cohorts
AUC: AL-794
Time frame: From baseline to Day 17 for Multiple Ascending Dose cohorts
CMax: Fed vs. Fasted
Time frame: First dose to Day 8 (Single Ascending Dose/Food Effect)
AUC: Fed vs. Fasted
Time frame: First dose to Day 8 (Single Ascending Dose/Food Effect)
Influenza Viral Load
Time frame: Baseline to Day 28
Peak influenza viral load after treatment
Time frame: inoculation to Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2017.
- Derived from this study: PubMed 30053042Yogaratnam 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.
- Derived from this study: PubMed 29927386Kakuda 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.
Related trials for Influenza
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
RecruitingPhase 2
BPL-1357 Against H1N1 Influenza Virus Challenge
Influenza, Human
Not yet recruitingPhase 1
Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates
Influenza
RecruitingPhase 1
pH1N1 Blinded Challenge Study
Influenza
RecruitingPhase 3
A Study to Evaluate the Safety and Efficacy of MK-1406/CD388 for Prevention of Influenza (MK-1406-005/CD388.SQ.3.06)
Influenza
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Malcolm Boyce principal investigator
HMR
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AL-794 in people with Influenza, run by Alios Biopharma Inc. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Data including but not limited to tabulation of adverse events, physical exam, vital signs, 12-lead ECGs and clinical lab results (time frame: Screening to Day 8 in Single Dose and Food Effect portions of the study). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02588521, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2017.