Chronic Hepatitits CPhase 1NCT02510248
First in Human Study of AL-704; Single Dose, Food Effect in Healthy Volunteers; Multiple Doses in Chronic Hepatitis C
A Phase 1 study testing AL-704 in people with Chronic Hepatitits C, run by Alios Biopharma Inc. at 3 sites in 3 countries.
Trial summary
This is a Phase 1, randomized, double-blind, placebo-controlled, first-in-human, 3-part study in which the safety, tolerability, and pharmacokinetics of orally administered AL-704 will be assessed in healthy adult subjects and in adult subjects with CHC infection. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Hepatitits C
- What is being tested?
- AL-704
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 31 Jul 2015to 24 Nov 2015
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject must be a man or woman 18 to 60 years of age, inclusive for healthy subjects, or 18 to 65 years of age, inclusive for subjects with CHC infection.
- Each subject must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study before starting any screening activities.
- Subject must be willing and able to adhere to the prohibitions and restrictions
- Subject included in Part 1 and 2 of the study, must be non-smokers for at least 3 months prior to screening.
- Subject included in Part 1 and 2 of the study, must be healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, vital signs, and the results of biochemistry, and hematology tests and a urinalysis performed at screening and admission. If there are abnormalities, the subject may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the Investigator.
- Subject with CHC infection included in Part 3 of the study, must be otherwise healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality other than those related to CHC infection, and includes a physical examination, medical history, vital signs, and the results of blood biochemistry, blood coagulation and hematology tests and a urinalysis performed at screening and admission. If there are abnormalities, the subject may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the Investigator and the Sponsor.
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- Subject included in Part 1 and 2 of the study, must have a body mass index (BMI) of 18.0 to 32.0 kg/m2, extremes included. Subjects with CHC infection included in Part 3 of the study must have a BMI of 18.0 to 35.0 kg/m2, extremes included, with a minimum weight of 50 kg in both populations. No more than 25% of patients in any cohort may be enrolled with a BMI ≥30 kg/m2.
- Female subject must be of non-childbearing potential.
- Female subject, except if postmenopausal, should have a negative serum pregnancy test at screening and a negative urine pregnancy test at admission.
- Subject must agree to comply with contraceptive measures .
- Subject must have a normal 12-lead ECG (based on the mean value of the triplicate parameters at admission)
- Additional inclusion criteria for CHC-infected subjects in Part 3 of the study:
- Documentation of HCV infection for longer than 6 months and determination of genotype 1 or 3 HCV infection at screening. In case of discrepancy between previously documented geno- or subtype and the geno- or subtype determined at screening, the eligibility results will be used to determine eligibility.
- HCV RNA viral load ≥105 IU/mL using a sensitive quantitative assay
Who cannot join
- Subject has a history or current clinically significant medical illness (except for
- CHC infection in subjects in Part 3 of the study) that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol-specified assessments. This may include but is not limited to renal dysfunction (calculated creatinine clearance below 60 mL/min at screening), significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances.
- Subject has a positive human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2) test at screening.
- Subject has hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin M [IgM]), or hepatitis B virus infection (confirmed by hepatitis B surface antigen [HBsAg]) at screening. Subject has current hepatitis C virus (HCV) infection (confirmed by HCV
- antibody) at screening, only applicable in Part 1 and 2 of the study.
- Subject has received an investigational agent (small molecule) or vaccine within 30 days, or having received a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to the planned intake of study drug.
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- Subject has a past history of heart arrhythmias (extrasystole, tachycardia at rest) or of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome).
- Subject has donated or lost more than 1 unit of blood (500 mL) within 60 days or more than one unit of plasma within 7 days prior to the first intake of study drug.
- Subject has evidence of active infection (other than CHC infection for subjects enrolled in Part 3).
- Subject has a positive urine drug test at study screening or admission.
- Additional exclusion criteria for CHC-infected subjects in Part 3 of the study:
- Subject with HCV RNA <105 IU/mL.
- Subject has a history of clinical hepatic decompensation, eg, variceal bleeding, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy or active jaundice.
- Subject has had a liver biopsy within 2 years or Fibroscan evaluation within 6 months prior to randomization that demonstrates cirrhosis (Knodell score >3, Metavir score >3, Ishak score >4). Fibroscan liver stiffness score >12.5 kPa.
- Subject has received prior treatment for CHC.
- Subject has ultrasound evidence consistent with or suspicious for hepatocellular carcinoma.
- Subject has alpha fetoprotein (AFP) >50 ng/mL, unless the absence of a hepatic mass or lesion is demonstrated by ultrasound within the screening period.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, First-in-human, 3-part Study of Orally Administered JNJ-54257099 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses (Part 1) and Food-effect (Part 2) in Healthy Subjects, and Multiple Doses in Subjects With Chronic Hepatitis C Infection (Part 3)
This is a Phase 1, randomized, double-blind, placebo-controlled, first-in-human, 3-part study in which the safety, tolerability, and pharmacokinetics of orally administered AL-704 will be assessed in healthy adult subjects and in adult subjects with CHC infection.
Part 1: Healthy adult subjects will receive one of 5 single ascending oral doses (SAD) of AL-704 ranging from 100 mg to 1,500 mg (Cohorts 1 to 5). Within each cohort subjects will be randomized to receive either AL-704 or placebo (n=8 per cohort; 6 assigned to AL-704 and 2 assigned to placebo), in a fasted state.
Read more
The planned dose-escalation scheme may be changed based on the emerging PK and safety data. Two additional cohorts (Cohorts 6 and 7) may be enrolled for evaluation of additional doses at the discretion of the Sponsor and Investigator, based on the emerging pharmacokinetic (PK) profile, and the presence of an acceptable safety profile.
Part 2: To assess the food effect on pharmacokinetics, 8 healthy subjects from one full Part 1 cohort who received a single dose of AL-704 or placebo in a fasted state, will receive the same single dose of AL-704 or placebo in a fed state in Part 2 after a washout period of 7-14 days (depending on PK results). It is expected that Cohort 3 of Part 1 (600 mg dose) will be selected, however this depends on the evaluation of available PK and safety data from Part 1 of the study.
Part 3: The following cohorts of 10 adult subjects each, with CHC infection, will be evaluated. Subjects with CHC genotype 1 infection (Cohorts 8 to 10) and subjects with CHC genotype 3 infection (Cohort 11) will be randomized to receive AL-704 or placebo for 7 consecutive days (n=10 per cohort, 8 assigned to AL-704 and 2 assigned to placebo) in a fed state. The treatment is anticipated to be administered in a once daily dose regimen or a twice daily dose regimen. The dose and dose regimen to be administered will be determined by the Sponsor depending on the PK and safety outcomes of previous cohorts.
- Conditions
- Chronic Hepatitits C
- Being tested
- AL-704, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AL-704Drug
Also called JNJ-54257099, ALS-022704
JNJ-54257099 (also known as ALS-022704 or AL-704) is a hepatitis C virus (HCV) nonstructural (NS)5B inhibitor, belonging to the nucleoside / nucleotide inhibitor class, and is being developed as an orally administered anti-HCV therapeutic.
PlaceboDrug
Placebo to match AL-704
| Study group | Role | What they receive |
|---|---|---|
| Study Drug | Experimental | Study drug will be AL-704 once or twice daily for up to 7 days in dosages ranging from 100 mg to 1500 mg. Receives: Drug: AL-704 |
| Placebo | Placebo comparator | Placebo to match study drug dosing. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Data assessed by Number and frequency of treatment emergent adverse events, physical examination findings
abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results examination findings, vital signs, ECG and clinical lab results
Measured: From screening to last visit (up to 21 days)
Secondary outcomes (3)
Single dose PK Profile from Cmax, tmax, t1/2, CL/F and Vz/F, AUC0-inf or AUClast
Measured: From dosing to Day 8 visit for each SAD/FE cohort
Multiple dose PK: profile from Cmax, tmax, t1/2, AUClast and AUC0 tau
Measured: From dosing to final study visit (21 days) for each cohort
Hepatitis C virus levels
HCV RNA viral load change from baseline to final study visit in subjects with Chronic hepatitis C infection
Measured: From screening to final study visit (21 days) for each cohort
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2015 (estimated)
- Study start31 Jul 2015
- Primary completion24 Nov 2015
- Study completion24 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitits CStudies 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
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alios Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen Pharmaceutica
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02510248
- Sponsor's protocol ID
- AL-704-701
- Status last verified
- Nov 2017
- First submitted
- 2 Jul 2015
- Last updated
- 8 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 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, 3-part Study of Orally Administered JNJ-54257099 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses (Part 1) and Food-effect (Part 2) in Healthy Subjects, and Multiple Doses in Subjects With Chronic Hepatitis C Infection (Part 3)
- ClinicalTrials.gov ID
- NCT02510248
- Acronym / sponsor ID
- AL-704-701
- Conditions
- Chronic Hepatitits C
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Alios Biopharma Inc.Industry (pharma, biotech, devices)
- Collaborators
- Janssen Pharmaceutica
- Study start
- 31 Jul 2015 (actual)
- Primary completion
- 24 Nov 2015 (actual)
- Study completion
- 24 Nov 2015 (actual)
- First posted
- 29 Jul 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 is a Phase 1, randomized, double-blind, placebo-controlled, first-in-human, 3-part study in which the safety, tolerability, and pharmacokinetics of orally administered AL-704 will be assessed in healthy adult subjects and in adult subjects with CHC infection.
Part 1: Healthy adult subjects will receive one of 5 single ascending oral doses (SAD) of AL-704 ranging from 100 mg to 1,500 mg (Cohorts 1 to 5). Within each cohort subjects will be randomized to receive either AL-704 or placebo (n=8 per cohort; 6 assigned to AL-704 and 2 assigned to placebo), in a fasted state.
The planned dose-escalation scheme may be changed based on the emerging PK and safety data. Two additional cohorts (Cohorts 6 and 7) may be enrolled for evaluation of additional doses at the discretion of the Sponsor and Investigator, based on the emerging pharmacokinetic (PK) profile, and the presence of an acceptable safety profile.
Part 2: To assess the food effect on pharmacokinetics, 8 healthy subjects from one full Part 1 cohort who received a single dose of AL-704 or placebo in a fasted state, will receive the same single dose of AL-704 or placebo in a fed state in Part 2 after a washout period of 7-14 days (depending on PK results). It is expected that Cohort 3 of Part 1 (600 mg dose) will be selected, however this depends on the evaluation of available PK and safety data from Part 1 of the study.
Part 3: The following cohorts of 10 adult subjects each, with CHC infection, will be evaluated. Subjects with CHC genotype 1 infection (Cohorts 8 to 10) and subjects with CHC genotype 3 infection (Cohort 11) will be randomized to receive AL-704 or placebo for 7 consecutive days (n=10 per cohort, 8 assigned to AL-704 and 2 assigned to placebo) in a fed state. The treatment is anticipated to be administered in a once daily dose regimen or a twice daily dose regimen. The dose and dose regimen to be administered will be determined by the Sponsor depending on the PK and safety outcomes of previous cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Drug | Experimental | Drug: AL-704Study drug will be AL-704 once or twice daily for up to 7 days in dosages ranging from 100 mg to 1500 mg. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo to match study drug dosing. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subject must be a man or woman 18 to 60 years of age, inclusive for healthy subjects, or 18 to 65 years of age, inclusive for subjects with CHC infection.
- Each subject must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study before starting any screening activities.
- Subject must be willing and able to adhere to the prohibitions and restrictions
- Subject included in Part 1 and 2 of the study, must be non-smokers for at least 3 months prior to screening.
- Subject included in Part 1 and 2 of the study, must be healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, vital signs, and the results of biochemistry, and hematology tests and a urinalysis performed at screening and admission. If there are abnormalities, the subject may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the Investigator.
Key exclusion criteria (17 listed)
- Subject has a history or current clinically significant medical illness (except for
- CHC infection in subjects in Part 3 of the study) that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol-specified assessments. This may include but is not limited to renal dysfunction (calculated creatinine clearance below 60 mL/min at screening), significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances.
- Subject has a positive human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2) test at screening.
- Subject has hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin M [IgM]), or hepatitis B virus infection (confirmed by hepatitis B surface antigen [HBsAg]) at screening. Subject has current hepatitis C virus (HCV) infection (confirmed by HCV
- antibody) at screening, only applicable in Part 1 and 2 of the study.
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-704Also: JNJ-54257099, ALS-022704JNJ-54257099 (also known as ALS-022704 or AL-704) is a hepatitis C virus (HCV) nonstructural (NS)5B inhibitor, belonging to the nucleoside / nucleotide inhibitor class, and is being developed as an orally administered anti-HCV therapeutic. | Drug | Study Drug |
| PlaceboPlacebo to match AL-704 | Drug | Placebo |
Primary outcome
Safety Data assessed by Number and frequency of treatment emergent adverse events, physical examination findings
Time frame: From screening to last visit (up to 21 days)
abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results examination findings, vital signs, ECG and clinical lab results
3 secondary outcomes
Single dose PK Profile from Cmax, tmax, t1/2, CL/F and Vz/F, AUC0-inf or AUClast
Time frame: From dosing to Day 8 visit for each SAD/FE cohort
Multiple dose PK: profile from Cmax, tmax, t1/2, AUClast and AUC0 tau
Time frame: From dosing to final study visit (21 days) for each cohort
Hepatitis C virus levels
Time frame: From screening to final study visit (21 days) for each cohort
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2017.
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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AL-704 in people with Chronic Hepatitits C, run by Alios Biopharma Inc. at 3 sites in 3 countries.
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 14 inclusion and 17 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: stopped early, as of the sponsor's last update on 8 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France, Georgia, Moldova. 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 was stopped early. Results are not available in the source record.
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 assessed by Number and frequency of treatment emergent adverse events, physical examination findings (time frame: From screening to last visit (up to 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Nov 2017; AzTrials last refreshed its copy on 7 Nov 2026.