Safety and Efficacy Study of Single Doses of TT-034 in Patients With Chronic Hepatitis C

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Tacere Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Tacere Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01899092
First received: July 8, 2013
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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 Once the study drug is given, it cannot be withdrawn.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.


Condition Intervention Phase
Hepatitis C
Drug: TT-034
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tacere Therapeutics, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • To determine the maximum tolerable dose or the optimal efficacy dose (whichever comes first) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • To determine the viral load [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the presence of viral escape mutants in subjects with detectable viral load after receiving TT-034 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To monitor TT-034 vector DNA levels and shRNA expression in the target organ (liver) after dosing with TT-034 [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  • To monitor TT-034 vector DNA levels and shRNA expression peripherally (in blood) after dosing with TT-034 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 14
Study Start Date: January 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Escalating Dose of TT-034
The study contains one dose escalation arm with active drug.
Drug: TT-034
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must a history of chronic HCV infection defined as documented HCV genotype 1 infection for at least 6 months.

  • Subjects must have:

    1. 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
    2. 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:

    1. Female subjects over the age 60.
    2. 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.
    3. 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

Exclusion Criteria:

  • Body mass index < 18.5 or > 30
  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01899092

Locations
United States, California
UCSD Antiviral Research Center Not yet recruiting
San Diego, California, United States, 92103
Contact: Amber Faulise    858-657-5175      
Principal Investigator: David Wyles, MD         
United States, North Carolina
Duke Clinical Research Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Vicki Robertson    919-613-6246    dcrurecruit@duke.edu   
Principal Investigator: Keyur Patel, MD         
Sponsors and Collaborators
Tacere Therapeutics, Inc.
Investigators
Study Director: David Suhy, PhD Tacere Therapeutics, Inc.
Principal Investigator: Keyur Patel, MD Duke Clinical Research Institute
Principal Investigator: David Wyles, MD University of California, San Diego
  More Information

No publications provided

Responsible Party: Tacere Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01899092     History of Changes
Other Study ID Numbers: B2801001
Study First Received: July 8, 2013
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tacere Therapeutics, Inc.:
Chronic Hepatitis C
Genotype 1
CHC
HCV
Hepatitis
RNAi
shRNA
ddRNAi
AAV8
AAV
Adeno-associated virus
Adeno-associated viral vectors

Additional relevant MeSH terms:
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis A
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on July 24, 2014