Hepatitis C Virus-infected CirrhosisPhase 1NCT02195440
An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis
A Phase 1 study testing PRI-724 in people with Hepatitis C Virus-infected Cirrhosis, run by Komagome Hospital at 1 site in Japan.
Trial summary
The purpose of this study is to investigate the safety and tolerability of PRI-724 in patients with HCV-induced cirrhosis. Read more about this study
- Who is it for?
- Ages 20 to 74 years
- Conditions the study is for
- Hepatitis C Virus-infected Cirrhosis
- What is being tested?
- PRI-724
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteJapan
- Study dates
- Aug 2014to 31 Mar 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 20 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presence of cirrhosis due to hepatitis C virus. 1) Serum HCV-RNA test positive 2) Definitive diagnosis of cirrhosis established by liver biopsy (HAI score: Grade IV-D).
- Child-Pugh Class A or B at the time of informed consent, with no likelihood of improvement with existing medical treatment.
- Performance Status: 0 - 2.
- Between =>20 and <75 years of age at the time of providing written consent.
- Having provided voluntary written consent for participation in this study.
- Esophageal and gastric varices are well controlled
Who cannot join
- Patients with cirrhosis due to causes other than hepatitis C virus; or patients with cirrhosis due to unknown causes.
- Patients with a history of primary liver cancer or a complication thereof.
- Patients with a complication of malignant tumor or a history thereof (within 5 years prior to screening).
- Patients in whom such active viral infections as HBV, HIV or ATCL or syphilis infection cannot be ruled out.
- Patients with serum creatinine >1.5 times over upper normal or creatinine clearance =<60 mL/min/1.73 m2.
- Patients with hemoglobin <8 g/dL.
Show all 19Show fewer
- Patients with platelet count <50,000 /\µL.
- Patients with T.Bil =>3.0 mg/dL.
- Patients with a complication of poorly controlled diabetes, hypertension or heart failure.
- Patients with a complication of mental disorder requiring treatment.
- Patients with serious allergy to contrast media or a history thereof.
- Patients with allergy to inactive ingredients of the study drug.
- Patients who have received interferon, ribavirin or anti-HCV agents within 12 weeks before registration in this study.
- When the medical treatment to a primary disease is carried out, Patient who was changed the dosage and administration within the 12 weeks before registration.
- Patients with a history of drug or alcohol addiction within five years at the time of providing written consent or a history of drug or alcohol abuse within the past one year.
- The patient who received a liver transplant or other organ transplants (a bone marrow transplantation is included), and the patient for whom intravenous administration and venous access are difficult.
- Patients contraindicated for liver biopsy.
- Female patients who are pregnant or suspected to be pregnant; or those who desire to get pregnant during the study period or those of childbearing potential.
- Male patients who do not consent to practice birth control during the clinical study.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to investigate the safety and tolerability of PRI-724 in patients with HCV-induced cirrhosis.
Read the detailed description
This is a single-center, open-label, continuous i.v. administration, dose escalation Phase I study in patients with hepatitis C cirrhosis.
One cycle consisted of one-week continuous i.v. administration of PRI-724 followed by a one-week observation period. One cohort was a total of six cycles, a 12-week treatment period.
PRI-724 was administered at a dose of 10 mg/m2/day in Cohort 1, 40 mg/m2/day in Cohort 2, and 160 mg/m2/day in Cohort 3 in a dose escalation manner. Each cohort was to include 6 subjects.
- Conditions
- Hepatitis C Virus-infected Cirrhosis
- Being tested
- PRI-724
- Keywords
- Hepatitis C virus, cirrhosis
- Medical subject headings
- Hepatitis C, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRI-724Drug
Also called CBP-beta-catennin inhibitor, OP-724
10 - 160 mg/m2, 7 days CIV (in the vein) with 7 days rest per one cycle. Number of Cycles: 6.
| Study group | Role | What they receive |
|---|---|---|
| PRI-724 | Experimental | 3 cohorts (PRI-724: 10, 40, 160 mg/m2/day), 6 cycles (1 cycle: 1-week continuous i.v. administration+1-week observation period)
*Cycle 2 will not be started until plasma drug concentrations of PRI-724 and C-82 on Days 1 and 2 in Cycle 1 are confirmed.
Cohort 1: 10 mg/m2/day (6 subjects) Cohort 2: 40 mg/m2/day (6 subjects) Cohort 3: 160 mg/m2/day (6 subjects) One cycle consists of 1-week continuous i.v. administration of PRI-724 followed by a 1-week observation period. The tolerability and safety after 6 cycles will be confirmed. Receives: Drug: PRI-724 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)
Items and ratio%
Measured: 12 weeks after the initiation of PRI-724 administration
Secondary outcomes (8)
Child-Pugh Score
Changes of score
Measured: 12 weeks after the initiation of PRI-724 administration
Liver biopsy: Histology Activity Index (HAI)
Changes of index
Measured: 12 weeks after the initiation of PRI-724 administration
Serum albumin level
Changes of level
Measured: 12 weeks after the initiation of PRI-724 administration
Serum fibrosis marker level(s)
Changes of level
Measured: 12 weeks after the initiation of PRI-724 administration
Ascitic fluid level
Changes of level
Measured: 12 weeks after the initiation of PRI-724 administration
Improvement rate of lower leg edema
Changes of rate
Measured: 12 weeks after the initiation of PRI-724 administration
Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples
Comparison of AUC
Measured: Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h
Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples
Comparison of Css
Measured: Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2014 (estimated)
- Study startAug 2014
- Primary completion31 Mar 2017
- Study completion31 Mar 2017
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 Hepatitis C Virus-infected CirrhosisStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Komagome Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Prism Pharma Co., Ltd., Japan Agency for Medical Research and Development
- Responsible party
- Principal investigator, Kiminori Kimura, MD, Komagome Hospital
- Investigators
- Kiminori Kimura, MD, Principal investigator, Komagome Metropolitan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02195440
- Sponsor's protocol ID
- PRI-724-1101
- Other IDs
- UMIN000014395
- Status last verified
- Jul 2022
- First submitted
- 8 Jul 2014
- Last updated
- 7 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kimura K, Ikoma A, Shibakawa M, Shimoda S, Harada K, Saio M, Imamura J, Osawa Y, Kimura M, Nishikawa K, Okusaka T, Morita S, Inoue K, Kanto T, Todaka K, Nakanishi Y, Kohara M, Mizokami M. Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/beta-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial. EBioMedicine. 2017 Sep;23:79-87. doi: 10.1016/j.ebiom.2017.08.016. Epub 2017 Aug 19.
PubMed 28844410
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis
- ClinicalTrials.gov ID
- NCT02195440
- Acronym / sponsor ID
- PRI-724-1101
- Conditions
- Hepatitis C Virus-infected Cirrhosis
- Keywords
- Hepatitis C virus, cirrhosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Komagome HospitalUniversity, hospital or other
- Collaborators
- Prism Pharma Co., Ltd., Japan Agency for Medical Research and Development
- Study start
- Aug 2014
- Primary completion
- 31 Mar 2017 (actual)
- Study completion
- 31 Mar 2017 (actual)
- First posted
- 21 Jul 2014 (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.
The purpose of this study is to investigate the safety and tolerability of PRI-724 in patients with HCV-induced cirrhosis.
Detailed description
This is a single-center, open-label, continuous i.v. administration, dose escalation Phase I study in patients with hepatitis C cirrhosis.
One cycle consisted of one-week continuous i.v. administration of PRI-724 followed by a one-week observation period. One cohort was a total of six cycles, a 12-week treatment period.
PRI-724 was administered at a dose of 10 mg/m2/day in Cohort 1, 40 mg/m2/day in Cohort 2, and 160 mg/m2/day in Cohort 3 in a dose escalation manner. Each cohort was to include 6 subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PRI-724 | Experimental | Drug: PRI-7243 cohorts (PRI-724: 10, 40, 160 mg/m2/day), 6 cycles (1 cycle: 1-week continuous i.v. administration+1-week observation period) *Cycle 2 will not be started until plasma drug concentrations of PRI-724 and C-82 on Days 1 and 2 in Cycle 1 are confirmed. Cohort 1: 10 mg/m2/day (6 subjects) Cohort 2: 40 mg/m2/day (6 subjects) Cohort 3: 160 mg/m2/day (6 subjects) One cycle consists of 1-week continuous i.v. administration of PRI-724 followed by a 1-week observation period. The tolerability and safety after 6 cycles will be confirmed. |
Who may qualify
- Ages
- 20 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Presence of cirrhosis due to hepatitis C virus. 1) Serum HCV-RNA test positive 2) Definitive diagnosis of cirrhosis established by liver biopsy (HAI score: Grade IV-D).
- Child-Pugh Class A or B at the time of informed consent, with no likelihood of improvement with existing medical treatment.
- Performance Status: 0 - 2.
- Between =>20 and <75 years of age at the time of providing written consent.
- Having provided voluntary written consent for participation in this study.
Key exclusion criteria (19 listed)
- Patients with cirrhosis due to causes other than hepatitis C virus; or patients with cirrhosis due to unknown causes.
- Patients with a history of primary liver cancer or a complication thereof.
- Patients with a complication of malignant tumor or a history thereof (within 5 years prior to screening).
- Patients in whom such active viral infections as HBV, HIV or ATCL or syphilis infection cannot be ruled out.
- Patients with serum creatinine >1.5 times over upper normal or creatinine clearance =<60 mL/min/1.73 m2.
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 |
|---|---|---|
| PRI-724Also: CBP-beta-catennin inhibitor, OP-72410 - 160 mg/m2, 7 days CIV (in the vein) with 7 days rest per one cycle. Number of Cycles: 6. | Drug | PRI-724 |
Primary outcome
Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)
Time frame: 12 weeks after the initiation of PRI-724 administration
Items and ratio%
8 secondary outcomes
Child-Pugh Score
Time frame: 12 weeks after the initiation of PRI-724 administration
Liver biopsy: Histology Activity Index (HAI)
Time frame: 12 weeks after the initiation of PRI-724 administration
Serum albumin level
Time frame: 12 weeks after the initiation of PRI-724 administration
Serum fibrosis marker level(s)
Time frame: 12 weeks after the initiation of PRI-724 administration
Ascitic fluid level
Time frame: 12 weeks after the initiation of PRI-724 administration
Improvement rate of lower leg edema
Time frame: 12 weeks after the initiation of PRI-724 administration
Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples
Time frame: Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h
Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples
Time frame: Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h
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 7 Jul 2022.
- Derived from this study: PubMed 28844410Kimura K, Ikoma A, Shibakawa M, Shimoda S, Harada K, Saio M, Imamura J, Osawa Y, Kimura M, Nishikawa K, Okusaka T, Morita S, Inoue K, Kanto T, Todaka K, Nakanishi Y, Kohara M, Mizokami M. Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/beta-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial. EBioMedicine. 2017 Sep;23:79-87. doi: 10.1016/j.ebiom.2017.08.016. Epub 2017 Aug 19.
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.
Kiminori Kimura, MD principal investigator
Komagome Metropolitan Hospital
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 PRI-724 in people with Hepatitis C Virus-infected Cirrhosis, run by Komagome Hospital at 1 site in Japan.
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 6 inclusion and 19 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 7 Jul 2022. 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 Japan. 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?
Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values) (time frame: 12 weeks after the initiation of PRI-724 administration). 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 NCT02195440, 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 7 Jul 2022.