Chronic Hepatitis CPhase 1NCT02512562
A Study to Evaluate the Effect of ACH-3102 and Simeprevir on AL-335 Pharmacokinetics in Healthy Volunteers
A Phase 1 study testing AL-335, ACH-3102 and Simeprevir in people with Chronic Hepatitis C, run by Alios Biopharma Inc. at 1 site in France.
Trial summary
This is an open-label, two-group, fixed-sequence study to evaluate the effect of ACH-3102 and Simeprevir on AL-335 pharmacokinetics in healthy volunteers. 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, ACH-3102 and Simeprevir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteFrance
- Study dates
- 31 Jul 2015to 31 Aug 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 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.
- Body mass index (BMI) 18-32 kg/m2, inclusive. The minimum weight is 50 kg. No more than 25% of subjects 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.
- If male, subject is surgically sterile or practicing specific forms of birth control until 6 months after the end of the study. Males must agree to refrain from sperm donation from check-in through 6 months after dosing.
- Willing to avoid prolonged sun exposure while taking SMV and through follow-up. Subjects should also be advised to use a broad spectrum sun screen and lip balm of at least sun protection factor (SPF) > 30 to help protect against potential sunburn.
Who cannot join
- Pregnant or nursing (lactating) females, confirmed by a positive HCG laboratory test or females contemplating pregnancy. Men whose female partners are pregnant or contemplating pregnancy from the date of screening until 6 months after their last dose of study drugs.
- 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 screening test for hepatitis B, C or HIV serology. Subjects previously infected with HCV and achieved a sustained virologic response with treatment (no detectable HCV RNA 6 months post treatment) are eligible.
- 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.
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- ECG with PR > 200 ms, QRS > 120 ms, QTcF > 450 ms, as assessed by centrally read 12 lead ECG 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.
- 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.
- Unwilling to abstain from alcohol for at least 1 week 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 the screening visit.
- History of tobacco use or used nicotine-containing products within 3 months of the screening visit.
- 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 is excluded, unless approved by the Sponsor's Medical Monitor. Occasional use of acetaminophen is permitted.
- Exposure to more than four new investigational entities within 12 months prior to the first dosing day.
- Hypersensitivity to the active substances or to any of the excipients of AL-335, ACH-3102 or SMV.
- Subjects of East Asian ancestry.
- Abnormal biochemistry or hematology laboratory results obtained at screening. Elevated bilirubin in subjects with suspected Gilbert's disease is allowed.
- Unwillingness or inability to comply with the study protocol for any other reason.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase-1, Open-label, Two Group, Fixed-Sequence Study to Evaluate the Effect of ACH-3102 and Simeprevir on AL-335 Pharmacokinetics in Healthy Volunteers
This is an open-label, two-group, fixed-sequence study to evaluate the effect of ACH-3102 and Simeprevir on AL-335 pharmacokinetics in healthy volunteers.
- Conditions
- Chronic Hepatitis C
- Being tested
- AL-335, ACH-3102, Simeprevir
- 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-335Drug
AL-335 is a prodrug being developed as an orally administered anti-HCV therapeutic.
ACH-3102Drug
ACH-3102 is an NS5A inhibitor being developed as an orally administered anti-HCV therapeutic.
SimeprevirDrug
Also called Olysio
Simeprevir is an orally active, small molecule inhibitor of the NS3/4A protease of HCV and indicated for the treatment of chronic HCV infection as a component of a combination antiviral treatment regimen.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: AL-335, Simeprevir and ACH-3102 | Active comparator | AL-335, ACH-3102, and Simeprevir dosed in healthy human volunteers once daily for 24 days. Receives: Drug: AL-335; Drug: ACH-3102; Drug: Simeprevir |
| Group 2: AL-335, Simeprevir and ACH-3102 | Active comparator | AL-335, ACH-3102, and Simeprevir dosed in healthy human volunteers once daily for 24 days. Receives: Drug: AL-335; Drug: ACH-3102; Drug: Simeprevir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multiple dose PK Profile, Cmax and AUC: effect of ACH-3102 on AL-335 and metabolites
To evaluate the effect of multiple oral doses of ACH-3102, on the multiple oral dose PK of AL-335 and metabolites
Measured: From screening to Day 28 follow-up visit
Multiple dose PK Profile, Cmax and AUC: effect of Simeprevir on AL-335 and metabolites
To evaluate the effect of multiple oral doses of Simeprevir, on the multiple oral dose PK of AL-335 and metabolites
Measured: From screening to Day 24 visit
Multiple dose PK Profile, Cmax and AUC: effect of ACH-3102 and Simeprevir on AL-335 and metabolites
To evaluate the effect of multiple oral doses of ACH-3102 and Simeprevir, on the multiple oral dose PK of AL-335 and metabolites
Measured: From screening to Day 28 follow-up visit
Secondary outcomes (3)
Safety Data: Composite 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 28 follow-up visit
Steady-state PK Profile from Clast, t1/2, Tmax, Tlast, CL/F, Vz/F, λz: effect of AL-335 and ACH-3102 on Simeprevir
To determine the potential effect of AL-335 and/or ACH-3102 on the steady-state PK of Simeprevir.
Measured: From screening to Day 28 follow-up visit
Steady-state PK Profile from Clast, t1/2, Tmax, Tlast, CL/F, Vz/F, λz: effect of AL-335 and Simeprevir on ACH-3102
To determine the potential effect of AL-335 and/or Simeprevir on the steady-state PK of ACH-3102.
Measured: From screening to Day 28 follow-up visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2015 (estimated)
- Study start31 Jul 2015
- Primary completion31 Aug 2015
- Study completion31 Aug 2015
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 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alios Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02512562
- Sponsor's protocol ID
- AL-335-602
- Status last verified
- Oct 2019
- First submitted
- 6 Jul 2015
- Last updated
- 16 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated device
- No
Publications
Valade E, Valenzuela B, Kakuda TN, Westland C, McClure MW, Ouwerkerk-Mahadevan S, Perez-Ruixo JJ, Ackaert O. Characterizing the Pharmacokinetic Interaction Between Simeprevir and Odalasvir in Healthy Volunteers Using a Population Modeling Approach. AAPS J. 2018 Oct 22;20(6):111. doi: 10.1208/s12248-018-0271-0.
PubMed 30350297Kakuda TN, McClure MW, Westland C, Vuong J, Homery MC, Poizat G, Viguerie L, Denot C, Patat A, Zhang Q, Hui J, Apelian D, Smith DB, Chanda SM, Fry J. Pharmacokinetics, safety, and tolerability of the 2- and 3-direct-acting antiviral combination of AL-335, odalasvir, and simeprevir in healthy subjects. Pharmacol Res Perspect. 2018 Apr 30;6(3):e00395. doi: 10.1002/prp2.395. eCollection 2018 Jun.
PubMed 29736243
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 Phase-1, Open-label, Two Group, Fixed-Sequence Study to Evaluate the Effect of ACH-3102 and Simeprevir on AL-335 Pharmacokinetics in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02512562
- Acronym / sponsor ID
- AL-335-602
- Conditions
- Chronic Hepatitis C
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Alios Biopharma Inc.Industry (pharma, biotech, devices)
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- 31 Jul 2015 (actual)
- Primary completion
- 31 Aug 2015 (actual)
- Study completion
- 31 Aug 2015 (actual)
- First posted
- 31 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 an open-label, two-group, fixed-sequence study to evaluate the effect of ACH-3102 and Simeprevir on AL-335 pharmacokinetics in healthy volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: AL-335, Simeprevir and ACH-3102 | Active comparator | Drug: AL-335, Drug: ACH-3102, Drug: SimeprevirAL-335, ACH-3102, and Simeprevir dosed in healthy human volunteers once daily for 24 days. |
| Group 2: AL-335, Simeprevir and ACH-3102 | Active comparator | Drug: AL-335, Drug: ACH-3102, Drug: SimeprevirAL-335, ACH-3102, and Simeprevir dosed in healthy human volunteers once daily for 24 days. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 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.
- Body mass index (BMI) 18-32 kg/m2, inclusive. The minimum weight is 50 kg. No more than 25% of subjects may be enrolled with a BMI ≥ 30 kg/m2.
Key exclusion criteria (20 listed)
- Pregnant or nursing (lactating) females, confirmed by a positive HCG laboratory test or females contemplating pregnancy. Men whose female partners are pregnant or contemplating pregnancy from the date of screening until 6 months after their last dose of study drugs.
- 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 screening test for hepatitis B, C or HIV serology. Subjects previously infected with HCV and achieved a sustained virologic response with treatment (no detectable HCV RNA 6 months post treatment) are eligible.
- 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.
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-335AL-335 is a prodrug being developed as an orally administered anti-HCV therapeutic. | Drug | Group 1: AL-335, Simeprevir and ACH-3102, Group 2: AL-335, Simeprevir and ACH-3102 |
| ACH-3102ACH-3102 is an NS5A inhibitor being developed as an orally administered anti-HCV therapeutic. | Drug | Group 1: AL-335, Simeprevir and ACH-3102, Group 2: AL-335, Simeprevir and ACH-3102 |
| SimeprevirAlso: OlysioSimeprevir is an orally active, small molecule inhibitor of the NS3/4A protease of HCV and indicated for the treatment of chronic HCV infection as a component of a combination antiviral treatment regimen. | Drug | Group 1: AL-335, Simeprevir and ACH-3102, Group 2: AL-335, Simeprevir and ACH-3102 |
Primary outcome
Multiple dose PK Profile, Cmax and AUC: effect of ACH-3102 on AL-335 and metabolites
Time frame: From screening to Day 28 follow-up visit
To evaluate the effect of multiple oral doses of ACH-3102, on the multiple oral dose PK of AL-335 and metabolites
Multiple dose PK Profile, Cmax and AUC: effect of Simeprevir on AL-335 and metabolites
Time frame: From screening to Day 24 visit
To evaluate the effect of multiple oral doses of Simeprevir, on the multiple oral dose PK of AL-335 and metabolites
Multiple dose PK Profile, Cmax and AUC: effect of ACH-3102 and Simeprevir on AL-335 and metabolites
Time frame: From screening to Day 28 follow-up visit
To evaluate the effect of multiple oral doses of ACH-3102 and Simeprevir, on the multiple oral dose PK of AL-335 and metabolites
3 secondary outcomes
Safety Data: Composite 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 28 follow-up visit
Steady-state PK Profile from Clast, t1/2, Tmax, Tlast, CL/F, Vz/F, λz: effect of AL-335 and ACH-3102 on Simeprevir
Time frame: From screening to Day 28 follow-up visit
Steady-state PK Profile from Clast, t1/2, Tmax, Tlast, CL/F, Vz/F, λz: effect of AL-335 and Simeprevir on ACH-3102
Time frame: From screening to Day 28 follow-up visit
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 30350297Valade E, Valenzuela B, Kakuda TN, Westland C, McClure MW, Ouwerkerk-Mahadevan S, Perez-Ruixo JJ, Ackaert O. Characterizing the Pharmacokinetic Interaction Between Simeprevir and Odalasvir in Healthy Volunteers Using a Population Modeling Approach. AAPS J. 2018 Oct 22;20(6):111. doi: 10.1208/s12248-018-0271-0.
- Derived from this study: PubMed 29736243Kakuda TN, McClure MW, Westland C, Vuong J, Homery MC, Poizat G, Viguerie L, Denot C, Patat A, Zhang Q, Hui J, Apelian D, Smith DB, Chanda SM, Fry J. Pharmacokinetics, safety, and tolerability of the 2- and 3-direct-acting antiviral combination of AL-335, odalasvir, and simeprevir in healthy subjects. Pharmacol Res Perspect. 2018 Apr 30;6(3):e00395. doi: 10.1002/prp2.395. eCollection 2018 Jun.
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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.
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-335, ACH-3102 and Simeprevir in people with Chronic Hepatitis C, run by Alios Biopharma Inc. at 1 site in France.
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 8 inclusion and 20 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 1 site in France. 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. 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?
Multiple dose PK Profile, Cmax and AUC: effect of ACH-3102 on AL-335 and metabolites (time frame: From screening to Day 28 follow-up visit). 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 NCT02512562, 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 16 Oct 2019.