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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01899092
Recruitment Status : Completed
First Posted : July 15, 2013
Last Update Posted : November 30, 2016
Sponsor:
Information provided by (Responsible Party):
Tacere Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE July 8, 2013
First Posted Date  ICMJE July 15, 2013
Last Update Posted Date November 30, 2016
Study Start Date  ICMJE January 2014
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2013)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2013)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 10, 2013)
  • To determine the maximum tolerable dose or the optimal efficacy dose (whichever comes first) [ Time Frame: 6 months ]
  • To determine the viral load [ Time Frame: 6 months ]
  • To assess the presence of viral escape mutants in subjects with detectable viral load after receiving TT-034 [ Time Frame: 6 months ]
  • To monitor TT-034 vector DNA levels and shRNA expression in the target organ (liver) after dosing with TT-034 [ Time Frame: 3 weeks ]
  • To monitor TT-034 vector DNA levels and shRNA expression peripherally (in blood) after dosing with TT-034 [ Time Frame: 6 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Single Doses of TT-034 in Patients With Chronic Hepatitis C
Official Title  ICMJE 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
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Escalating Dose of TT-034
The study contains one dose escalation arm with active drug.
Intervention: Drug: TT-034
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 3, 2016)
9
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2013)
14
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01899092
Other Study ID Numbers  ICMJE B2801001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Tacere Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Tacere Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Suhy, PhD Tacere Therapeutics, Inc.
PRS Account Tacere Therapeutics, Inc.
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP