Hepatitis CPhase 1/2NCT01899092
Safety and Efficacy Study of Single Doses of TT-034 in Patients With Chronic Hepatitis C
A Phase 1/2 study testing TT-034 in people with Hepatitis C, run by Tacere Therapeutics, Inc. at 4 sites in United States.
Trial summary
The study is a first in man, dose escalation study that will measure the safety and efficacy of TT-034 in the treatment of patients with chronic hepatitis C. The study is divided into 5 dose levels. Subjects will be given a single dose delivered by IV infusion. The subjects will be monitored and the data analyzed. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- TT-034
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2014to Nov 2016
- Phase
- Phase 1/2
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must a history of chronic HCV infection defined as documented HCV genotype 1 infection for at least 6 months.
- Subjects must have:
- Documented failure to respond to prior treatment or relapse with a combination of peg-interferon (peg-IFN), ribavirin (RBV), and either boceprevir or telaprevir, OR a combination of peg-IFN and ribavirin or
- Subject is ineligible or unwilling to receive a combination of peg-IFN, RBV, and either boceprevir or telaprevir.
- Female subjects have to be of non-childbearing potential, defined as meeting any of the following criteria:
- Female subjects over the age 60.
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- Female subjects aged 45-60 years old must be amenorrhoeic for at least 2 years and must have serum follicle stimulating hormone (FSH) levels > 30 IU/L.
- Female subjects with hysterectomy or bilateral oophorectomy. All female subjects must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline.
- Male subjects and their partners must be willing to comply with the following requirements to use 2 methods of effective contraception: Male subjects with a vasectomy must use a condom. Without a vasectomy, male subjects must use a condom. The female must be sterile or willing to use an additional form of contraception.
- Baseline HCV RNA level of > 100,000 IU/mL and:
- No evidence of cirrhosis at Screening
- At least 3 months since prior therapy for HCV
- A willingness to enroll in a 5 year follow-up safety study
Who cannot join
- Body mass index < 18.5 or > 30
- Total body weight > 80 KG
- Female subjects of childbearing potential (including females with tubal ligation) or women who are pregnant or nursing
- Male subjects who are unwilling to provide the required semen samples
- Presence of nAb levels to AAV8 that abrogate AAV8 transduction
- Severe Liver disease
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- Hepatocellular carcinoma (HCC) or suspicion of HCC
- Coronary artery disease
- Platelet count of < 150 x 109/L or Creatinine ≥ 1.5 mg/dL at Screening
- Hypertension with systolic blood pressure consistently ≥ 130 mmHg or diastolic blood pressure consistently ≥ 90 mmHg
- Screening examinations indicative of possible occult malignancy unless cancer has been excluded
- Family history of colon cancer in any first-degree relative unless ruled out by colonoscopy
- Positive for human immunodeficiency virus 1 (HIV1) or HIV2 antibody
- Co-infection with hepatitis B virus
- History of autoimmune disease
- Renal impairment
- Hospitalization for liver disease within 60 days of Screening
- Use of drugs of abuse in the prior 3 months
- Other concomitant disease or condition likely to significantly decrease life expectancy or cancer
- Treatment with an investigational drug within 6 months preceding the first dose of trial medication
- Received an AAV vector previously or any other gene transfer agent in the previous 6 months
- History of cardiac abnormalities, as assessed at the Screening Visit
- Twelve-lead ECG demonstrating QTcB > 465 ms at Screening
- Chronic hepatic diseases
- Evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, neurologic, or allergic diseases.
- Evidence of autoimmune disease or pre-existing autoimmune or antibody-mediated diseases
- Use of immunosuppressive medications within 6 months before the entry into this study, except for inhaled or topical corticosteroids
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The Liver Institute at Methodist Dallas
Dallas, Texas, 75203
Duke Clinical Research Institute
Durham, North Carolina, 27710
The Texas Liver Institute
San Antonio, Texas, 78215
UCSD Antiviral Research Center
San Diego, California, 92103
About this study
Official title: A Phase I,II Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of Single Doses of TT-034 for Subjects With Chronic Hepatitis C (CHC) Infection
The study is a first in man, dose escalation study that will measure the safety and efficacy of TT-034 in the treatment of patients with chronic hepatitis C. The study is divided into 5 dose levels. Subjects will be given a single dose delivered by IV infusion. The subjects will be monitored and the data analyzed. After a set time, between 6 and 10 weeks depending on the dose level, the next set of subjects will be dosed. The study drug is a gene therapy treatment that produces molecules that destroy the Hepatitis C virus (HCV) in infected cells. Once the study drug is given, it cannot be withdrawn. Additionally, once an individual receives a dose, he or she will not be able to receive a second dose, but will remain eligible to receive most other HCV treatments.
Read the detailed description
This is a first-time use of a method of therapy designed to transfer anti-HCV genetic sequences into the hepatocytes of subjects infected with HCV. The anti-HCV sequences will be comprised of three different short hairpin RNAs (shRNA) that have the ability to directly cleave the RNA genome of HCV by a process known as RNA interference. The transfer of the anti-HCV sequences will be accomplished using a "vector" that was made from an adenovirus-associated virus (AAV) by removing the viral genes and replacing them with a non-replicating genetic sequence that produces three different shRNA that target three different regions within the HCV genes. This type of vector has been used in other clinical trials in order to transduce the hepatocytes of subjects who suffer from hemophilia.
- Conditions
- Hepatitis C
- Being tested
- TT-034
- Keywords
- Genotype 1, Chronic Hepatitis C, CHC, HCV, Hepatitis, RNAi, shRNA, ddRNAi, AAV8, AAV, Adeno-associated virus, Adeno-associated viral vectors
- Medical subject headings
- Hepatitis C, Hepatitis C, Chronic, Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TT-034Drug
The study drug will be given as a single dose IV infusion on Day 1. 5 different dose levels corresponding to the 5 cohorts of the study will be given.
| Study group | Role | What they receive |
|---|---|---|
| Escalating Dose of TT-034 | Experimental | The study contains one dose escalation arm with active drug. Receives: Drug: TT-034 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective is to assess the safety and tolerability of single escalating doses of TT-034 administered IV as a single infusion to subjects with CHC.
Measured: 6 months
Secondary outcomes (1)
To assess the activity of TT-034 on the viral load of subjects with CHC receiving single escalating doses of TT-034
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2013 (estimated)
- Study startJan 2014
- Primary completionSep 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tacere Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Suhy, PhD, Study director, Tacere Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01899092
- Sponsor's protocol ID
- B2801001
- Status last verified
- Nov 2016
- First submitted
- 8 Jul 2013
- Last updated
- 30 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I,II Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of Single Doses of TT-034 for Subjects With Chronic Hepatitis C (CHC) Infection
- ClinicalTrials.gov ID
- NCT01899092
- Acronym / sponsor ID
- B2801001
- Conditions
- Hepatitis C
- Keywords
- Genotype 1, Chronic Hepatitis C, CHC, HCV, Hepatitis, RNAi, shRNA, ddRNAi
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Tacere Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Sep 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 15 Jul 2013 (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 study is a first in man, dose escalation study that will measure the safety and efficacy of TT-034 in the treatment of patients with chronic hepatitis C. The study is divided into 5 dose levels. Subjects will be given a single dose delivered by IV infusion. The subjects will be monitored and the data analyzed. After a set time, between 6 and 10 weeks depending on the dose level, the next set of subjects will be dosed. The study drug is a gene therapy treatment that produces molecules that destroy the Hepatitis C virus (HCV) in infected cells. Once the study drug is given, it cannot be withdrawn. Additionally, once an individual receives a dose, he or she will not be able to receive a second dose, but will remain eligible to receive most other HCV treatments.
Detailed description
This is a first-time use of a method of therapy designed to transfer anti-HCV genetic sequences into the hepatocytes of subjects infected with HCV. The anti-HCV sequences will be comprised of three different short hairpin RNAs (shRNA) that have the ability to directly cleave the RNA genome of HCV by a process known as RNA interference. The transfer of the anti-HCV sequences will be accomplished using a "vector" that was made from an adenovirus-associated virus (AAV) by removing the viral genes and replacing them with a non-replicating genetic sequence that produces three different shRNA that target three different regions within the HCV genes. This type of vector has been used in other clinical trials in order to transduce the hepatocytes of subjects who suffer from hemophilia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Escalating Dose of TT-034 | Experimental | Drug: TT-034The study contains one dose escalation arm with active drug. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Subjects must a history of chronic HCV infection defined as documented HCV genotype 1 infection for at least 6 months.
- Subjects must have:
- Female subjects have to be of non-childbearing potential, defined as meeting any of the following criteria:
- Male subjects and their partners must be willing to comply with the following requirements to use 2 methods of effective contraception: Male subjects with a vasectomy must use a condom. Without a vasectomy, male subjects must use a condom. The female must be sterile or willing to use an additional form of contraception.
- Baseline HCV RNA level of > 100,000 IU/mL and:
Key exclusion criteria (27 listed)
- Body mass index < 18.5 or > 30
- Total body weight > 80 KG
- Female subjects of childbearing potential (including females with tubal ligation) or women who are pregnant or nursing
- Male subjects who are unwilling to provide the required semen samples
- Presence of nAb levels to AAV8 that abrogate AAV8 transduction
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 |
|---|---|---|
| TT-034The study drug will be given as a single dose IV infusion on Day 1. 5 different dose levels corresponding to the 5 cohorts of the study will be given. | Drug | Escalating Dose of TT-034 |
Primary outcome
The primary objective is to assess the safety and tolerability of single escalating doses of TT-034 administered IV as a single infusion to subjects with CHC.
Time frame: 6 months
1 secondary outcome
To assess the activity of TT-034 on the viral load of subjects with CHC receiving single escalating doses of TT-034
Time frame: 6 months
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 30 Nov 2016.
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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.
David Suhy, PhD study director
Tacere Therapeutics, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TT-034 in people with Hepatitis C, run by Tacere Therapeutics, Inc. at 4 sites in United States.
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 13 inclusion and 27 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 30 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The primary objective is to assess the safety and tolerability of single escalating doses of TT-034 administered IV as a single infusion to subjects with CHC. (time frame: 6 months). 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 30 Nov 2016.