Chronic Hepatitis CPhase 1NCT02339207
First in Human Study of AL-335; Single Dose, Food Effect in Healthy Volunteers; Multiple Doses in Chronic Hepatitis C Genotype 1
A Phase 1 study testing AL-335 in people with Chronic Hepatitis C, run by Alios Biopharma Inc. at 3 sites in 3 countries.
Trial summary
This randomized, double-blind, placebo-controlled, 3-part study will assess the safety, tolerability, and pharmacokinetics of orally administered AL-335 in healthy volunteers (HV) and subjects with CHC infection. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- AL-335
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 31 Dec 2014to 31 May 2016
- 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 for HV and 18-65 years of age for subjects with CHC.
- Body mass index (BMI) 18-32 kg/m2, inclusive, for HV and 18-35 kg/m2, inclusive, for subjects with CHC. The minimum weight is 50 kg in both populations. No more than 25% of patients in any cohort may be enrolled with a BMI ≥ 30 kg/m2.
- A female subject is eligible to participate in this study if she is of non childbearing potential (defined as females with a documented tubal ligation, bilateral oophorectomy, or hysterectomy) or postmenopausal (defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females). A post-menopausal female receiving hormone replacement therapy who is willing to discontinue hormone therapy 28 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation.
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- If male, subject is surgically sterile or practicing specific forms of birth control (as outline in Section 6.2.9) until 90 days after the end of the study.
- Additional inclusion criteria for subjects with CHC infection:
- Documentation of Genotype 1 HCV infection for greater than 6 months at dosing
- Screening HCV RNA viral load ≥ 105 IU/mL using a sensitive quantitative assay, such as COBAS® Taqman® HCV Test 2.0
Who cannot join
- Clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid, or any other medical illness or psychiatric disorder, as determined by the Investigator and/or Sponsor's Medical Monitor.
- Positive test for HAV IgM, HBsAg, or HIV Ab. In Parts 1 and 2 positive HCV serology is exclusionary.
- 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 30 days or 5 half lives (whichever is longer) prior to study medication.
- Clinically significant abnormal ECG findings. Particularly, a history or family history of prolonged QT syndrome (e.g., torsade de pointes) or sudden cardiac death; or a corrected QT interval (QTc) > 450 milliseconds for male subjects and >470 milliseconds for female subjects at the Screening Visit.
- Clinically significant blood loss or elective blood donation of significant volume (i.e., > 500 mL) within 60 days of first dose of study drug; > 1 unit of plasma within 7 days of first dose of study drug.
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- Abnormal heart rate, respiratory rate, temperature or blood pressure values outside of the normal range (evaluated in a semi-recumbent or recumbent position after 5 minutes of rest). One repeat measurement after an additional 5 minutes of rest is permitted.
- Evidence of active infection (other than CHC infection in subjects enrolled in Part 3).
- Unwilling to abstain from alcohol for 48 hours prior to the start of dosing through the study completion visit.
- History of regular alcohol intake > 7 units per week of alcohol for females and > 14 units per week for males (one unit is defined as 10 g alcohol) within 3 months of screening visit.
- For healthy subjects (Parts 1-2), history of regular use of tobacco (i.e., ≥10 cigarettes per day) or nicotine-containing products within 3 months of the screening visit. For subjects with CHC infection, history of regular use of tobacco- or nicotine-containing products is allowed.
- The subject has a positive pre-study drug screen. A minimum list of drugs that will be screened for includes amphetamines, barbiturates, cocaine, opiates, cannabinoids, phencyclidine (PCP) and benzodiazepines. Subjects with CHC may be included if they have a positive result for cannabinoids at screening. However, they must be willing to abstain from cannabinoid use throughout the duration of the study.
- In Parts 1-2, the use of concomitant medications, including prescription, over the counter medications, or herbal medications within 14 days prior to the first dose of study medication is excluded, unless approved by the Sponsor's Medical Monitor. PRN use of a nonsteroidal anti inflammatory drug (NSAID) is permitted.
- For subjects in Part 3, the use of prescription and over the counter medications deemed necessary to maintain the health status of the subject are permitted, if approved by the Sponsor's Medical Monitor. PRN NSAID use is permitted. Further guidance for the use of prior medication in subjects with CHC can be found in Section 5.7.
- Subjects must not have received any drug known to be a strong inducer or inhibitor of CYP450 enzymes within 2 weeks prior to study drug dosing (Appendix C).
- Exposure to more than four new investigational entities within 12 months prior to the first dosing day.
- Abnormal biochemistry or hematology laboratory results obtained at screening. Elevated bilirubin in subjects with suspected Gilbert's disease is allowed.
- Additional exclusion criteria for subjects with CHC infection:
- History of clinical hepatic decompensation, e.g., variceal bleeding, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy or active jaundice
- Liver biopsy within two 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 > 10.5 kPa.
- Prior treatment for CHC
- Serum alanine aminotransferase (ALT) concentration >5 x ULN
- Alpha Fetoprotein (AFP) is ≥ ULN, 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 AL-335 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Dosing and Food-effect in Healthy Volunteers, and Multiple Ascending Dosing in Subjects With Chronic Hepatitis C Genotype 1 Infection
This randomized, double-blind, placebo-controlled, 3-part study will assess the safety, tolerability, and pharmacokinetics of orally administered AL-335 in healthy volunteers (HV) and subjects with CHC infection.
- Conditions
- Chronic Hepatitis C
- Being tested
- AL-335 matching placebo, AL-335
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AL-335 matching placeboDrug
AL-335Drug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo dosed once in human volunteers in increasing dosages or once daily for seven days in patients with chronic Hepatitis C in increasing dosages. Receives: Drug: AL-335 matching placebo |
| AL-335 | Experimental | AL-335 dosed once in human volunteers in increasing dosages or once daily for seven days in patients with chronic Hepatitis C in increasing dosages. Receives: Drug: AL-335 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Data: Number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results
Tabulation of the number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results (including chemistry, hematology, and urine).
Measured: From screening to Day 8 (SAD/FE) and Day 21 (MAD)
Secondary outcomes (3)
Single Dose PK: Cmax, tmax, t1/2, CL/F and Vz/F (for AL-335 only), AUC0-inf or AUClast
PK parameters of AL-335, and metabolites following single dose administration: Cmax, tmax, t1/2, CL/F and Vz/F (for AL-335 only), AUC0-inf or AUClast
Measured: From dosing to Day 8 visit for each SAD/FE cohort
Multiple Dose PK: Cmax, tmax, t1/2, AUClast and AUC0 tau
- PK parameters of AL-335, ALS-022399, ALS-022227 (and other metabolites if applicable) following repeat dose administration: Cmax, tmax, t1/2, AUClast and AUC0 tau
Measured: From dosing to final study visit (21 days) for each cohort
Hepatitis C viral levels
HCV ribonucleic acid (RNA) viral load change from baseline to final study visit in subjects with CHC 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 posted15 Jan 2015 (estimated)
- Study start31 Dec 2014
- Primary completion31 May 2016
- Study completion31 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis 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
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alios Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02339207
- Sponsor's protocol ID
- AL-335-601
- Status last verified
- Oct 2019
- First submitted
- 18 Dec 2014
- Last updated
- 16 Oct 2019
- Results posted
- No
- FDA-regulated device
- No
Publications
McClure MW, Berliba E, Tsertsvadze T, Streinu-Cercel A, Vijgen L, Astruc B, Patat A, Westland C, Chanda S, Zhang Q, Kakuda TN, Vuong J, Khorlin N, Beigelman L, Blatt LM, Fry J. Safety, tolerability, and pharmacokinetics of AL-335 in healthy volunteers and hepatitis C virus-infected subjects. PLoS One. 2018 Oct 16;13(10):e0204974. doi: 10.1371/journal.pone.0204974. eCollection 2018.
PubMed 30325939
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2019. 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 AL-335 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Dosing and Food-effect in Healthy Volunteers, and Multiple Ascending Dosing in Subjects With Chronic Hepatitis C Genotype 1 Infection
- ClinicalTrials.gov ID
- NCT02339207
- Acronym / sponsor ID
- AL-335-601
- Conditions
- Chronic Hepatitis C
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Alios Biopharma Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Dec 2014 (actual)
- Primary completion
- 31 May 2016 (actual)
- Study completion
- 31 May 2016 (actual)
- First posted
- 15 Jan 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, 3-part study will assess the safety, tolerability, and pharmacokinetics of orally administered AL-335 in healthy volunteers (HV) and subjects with CHC infection.
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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: AL-335 matching placeboPlacebo dosed once in human volunteers in increasing dosages or once daily for seven days in patients with chronic Hepatitis C in increasing dosages. |
| AL-335 | Experimental | Drug: AL-335AL-335 dosed once in human volunteers in increasing dosages or once daily for seven days in patients with chronic Hepatitis C in increasing dosages. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 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 for HV and 18-65 years of age for subjects with CHC.
- Body mass index (BMI) 18-32 kg/m2, inclusive, for HV and 18-35 kg/m2, inclusive, for subjects with CHC. The minimum weight is 50 kg in both populations. No more than 25% of patients in any cohort may be enrolled with a BMI ≥ 30 kg/m2.
Key exclusion criteria (23 listed)
- Clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid, or any other medical illness or psychiatric disorder, as determined by the Investigator and/or Sponsor's Medical Monitor.
- Positive test for HAV IgM, HBsAg, or HIV Ab. In Parts 1 and 2 positive HCV serology is exclusionary.
- 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 30 days or 5 half lives (whichever is longer) prior to study medication.
- Clinically significant abnormal ECG findings. Particularly, a history or family history of prolonged QT syndrome (e.g., torsade de pointes) or sudden cardiac death; or a corrected QT interval (QTc) > 450 milliseconds for male subjects and >470 milliseconds for female subjects at the Screening Visit.
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-335 matching placebo | Drug | Placebo |
| AL-335 | Drug | AL-335 |
Primary outcome
Safety Data: Number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results
Time frame: From screening to Day 8 (SAD/FE) and Day 21 (MAD)
Tabulation of the number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results (including chemistry, hematology, and urine).
3 secondary outcomes
Single Dose PK: Cmax, tmax, t1/2, CL/F and Vz/F (for AL-335 only), AUC0-inf or AUClast
Time frame: From dosing to Day 8 visit for each SAD/FE cohort
Multiple Dose PK: Cmax, tmax, t1/2, AUClast and AUC0 tau
Time frame: From dosing to final study visit (21 days) for each cohort
Hepatitis C viral levels
Time frame: From screening to final study visit (21 days) for each cohort
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 16 Oct 2019.
- Derived from this study: PubMed 30325939McClure MW, Berliba E, Tsertsvadze T, Streinu-Cercel A, Vijgen L, Astruc B, Patat A, Westland C, Chanda S, Zhang Q, Kakuda TN, Vuong J, Khorlin N, Beigelman L, Blatt LM, Fry J. Safety, tolerability, and pharmacokinetics of AL-335 in healthy volunteers and hepatitis C virus-infected subjects. PLoS One. 2018 Oct 16;13(10):e0204974. doi: 10.1371/journal.pone.0204974. eCollection 2018.
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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-335 in people with Chronic Hepatitis 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 10 inclusion and 23 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 16 Oct 2019. 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 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: Number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results (time frame: From screening to Day 8 (SAD/FE) and Day 21 (MAD)). 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 NCT02339207, which also lists 1 linked publication.
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 16 Oct 2019.