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

• ClinicalTrials.gov Identifier: NCT01899092
• Recruitment Status: Completed
• First Posted: July 15, 2013
• Last Update Posted: November 30, 2016
• Sponsor: Tacere Therapeutics, Inc.
• Information provided by (Responsible Party): Tacere Therapeutics, Inc.

Tracking Information

• First Submitted Date: July 8, 2013
• First Posted Date: July 15, 2013
• Last Update Posted Date: November 30, 2016
• Study Start Date: January 2014
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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: Same as current
• Current Secondary Outcome Measures (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: 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: Safety and Efficacy Study of Single Doses of TT-034 in Patients With Chronic Hepatitis C
• 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
• 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis C

Intervention

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

Experimental: Escalating Dose of TT-034

The study contains one dose escalation arm with active drug.

Intervention: Drug: TT-034

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 3, 2016): 9
• Original Estimated Enrollment (submitted: July 10, 2013): 14
• Actual Study Completion Date: November 2016
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Eligibility 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
• 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

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01899092
• Other Study ID Numbers: B2801001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Tacere Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tacere Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: David Suhy, PhD; Tacere Therapeutics, Inc.

• PRS Account: Tacere Therapeutics, Inc.
• Verification Date: November 2016