Staged Phase I/II Hepatitis C Prophylactic Vaccine

NCT01436357 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 10-0069
• Study Type: interventional
• Target: 548
• Locations: 1 country
• Sites: 5

Brief Summary

A two stage, phase I/II, double-blinded, randomized, placebo-controlled study of hepatitis C virus (HCV)uninfected male and female injection drug users (IDU) aged 18 to 45. AdCh3NSmut1 and MVA-NSMut HCV vaccine will be administered to 68 (+/-4) volunteers in stage 1. A planned interim analysis of safety and immunogenicity will be conducted. If no safety signal is detected and there is evidence of a measurable immune response to HCV then 472 (+/-4) volunteers will be enrolled in stage 2. Primary objectives are to 1) assess the safety of AdCh3NSmut1 and MVA-NSmut compared to placebo when administered to HCV-uninfected IDUs and 2) determine if AdCh3NSmut1 and MVA-NSmut HCV vaccines will reduce incidence of chronic HCV infection compared to placebo among HCV-uninfected IDUs. Planned study duration is approx 63 months (accrual time, 2 months vaccination, 18 months follow-up, and 9 months extended observation for subjects becoming viremic in the last month of follow-up).

Conditions

Hepatitis C

Keywords

AdCh3NSmut1; Hepatitis C; MVA-NSmut; vaccine

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Chronic Hepatitis C Virus (HCV) Infection at 6 Months

  Chronic hepatitis C virus (HCV) infection was defined by persistent viremia over a period of 6 months after initial detection of primary infection.

  6 months

• Number of Participants With Clinical Safety Laboratory Adverse Events (AEs) at 1 Month After First Vaccination

  Blood was collected at baseline and 1 month after each vaccination for assessment of alanine transferase (ALT) (SGPT), creatinine, hemoglobin, platelets, and white blood cells (WBC). A laboratory AE was defined for ALT as greater than 1.25 times the upper limit of normal. A laboratory AE was defined for creatinine as greater than or equal to 1.2 times the upper limit of normal (as appropriate for age and sex). A laboratory AE was defined for hemoglobin as less that or equal to 12.4 g/dl for males and less than or equal to 10.8 g/dl for females. A laboratory AE was defined for platelets as less than or equal to 117,000 per cumm. A laboratory AE was defined for WBC as less than or equal to 2.9 thou/mcl or greater than or equal to 11.9 thou/mcl.

  1 month after first vaccination

• Number of Participants With Clinical Safety Laboratory Adverse Events (AEs) at 1 Month After Second Vaccination

  Blood was collected at baseline and 1 month after each vaccination for assessment of alanine transferase (ALT) (SGPT), creatinine, hemoglobin, platelets, and white blood cells (WBC). A laboratory AE was defined for ALT as greater than 1.25 times the upper limit of normal. A laboratory AE was defined for creatinine as greater than or equal to 1.2 times the upper limit of normal (as appropriate for age and sex). A laboratory AE was defined for hemoglobin as less that or equal to 12.4 g/dl for males and less than or equal to 10.8 g/dl for females. A laboratory AE was defined for platelets as less than or equal to 117,000 per cumm. A laboratory AE was defined for WBC as less than or equal to 2.9 thou/mcl or greater than or equal to 11.9 thou/mcl.

  1 month after second vaccination

• Number of Participants With Severe Local and/or Systemic Solicited Reactogenicity Signs and Symptoms in the 8 Days (Day 0-7) After First Vaccination

  Participants recorded temperature and the presence and intensity of post-vaccination reactogenicity events daily on an 8-day memory aid. Local solicited reactogenicity events included pain, tenderness, erythema, induration and warmth at the injection site. Systemic solicited reactogenicity events included fever, chills, arthralgia/joint pain, malaise/fatigue, myalgia/body aches, headache, nausea, vomiting, abdominal pain. Severe was defined as "events interrupt a subject's usual daily activity and may require systemic drug therapy or other treatment. Severe events are usually incapacitating." Measured erythema and induration of \>50 mm and oral temperature \>40.0 degrees Celsius were considered severe.

  7 days after first vaccination

• Occurrence of Vaccine-related Serious Adverse Events (SAEs) From the Time of First Vaccination Through the Entire Study Period

  The occurrence of SAEs was assessed at every study visit. The occurrence of SAEs may also have come to the attention of the investigator by secondary contacts of the participant when they did not present for study visits. Relationship to vaccine was assessed by the site investigator.

  Day 0 to 29 months

• Number of Participants With Severe Local and/or Systemic Solicited Reactogenicity Signs and Symptoms in the 8 Days (Day 0-7) After Second Vaccination

  Participants recorded temperature and the presence and intensity of post-vaccination reactogenicity events daily on an 8-day memory aid. Local solicited reactogenicity events included pain, tenderness, erythema, induration and warmth at the injection site. Systemic solicited reactogenicity events included fever, chills, arthralgia/joint pain, malaise/fatigue, myalgia/body aches, headache, nausea, vomiting, abdominal pain. Severe was defined as "events interrupt a subject's usual daily activity and may require systemic drug therapy or other treatment. Severe events are usually incapacitating." Measured erythema and induration of \>50 mm and oral temperature \>40.0 degrees Celsius were considered severe.

  7 days after second vaccination

Secondary Outcomes (1)

• Number of Participants With Positive Cell Mediated Immune Response

  Within 14 days after the last vaccination (Day 56)

Study Arms (2)

Arm A (Stage I and II)

EXPERIMENTAL

Receive AdCh3NSmut1 at 2.5 x 10\^10 total virus particles (vp)/dose at day 0 followed by 1 dose of MVA-NSmut intramuscularly 56 days later at the dosage 1.8 x10\^8 plaque forming units (pfu): 34 (+/-2) subjects Stage I, then 191 (+/-2) subjects at Stage II.

Biological: AdCh3NSmut1; Biological: MVA-NSmut

Arm B (Stage I and II)

PLACEBO COMPARATOR

Two doses of placebo intramuscularly, 1 at day 0 and 1 at day 56: 34 (+/-2) subjects Stage I, then 191 (+/-2) subjects at Stage II.

Other: Placebo

Interventions

AdCh3NSmut1 BIOLOGICAL

Stages I and II: Receive AdCh3NSmut1 at 2.5 x 10\^10 total virus particles (vp)/dose, intramuscularly on day 0.

Arm A (Stage I and II)

MVA-NSmut BIOLOGICAL

Stages I and II: 1 dose of MVA-NSmut at the dosage 1.8 x10\^8 plaque forming units (pfu) intramuscularly on day 56.

Arm A (Stage I and II)

Placebo OTHER

Stages I and II: Two doses of placebo intramuscularly, 1 at day 0 and 1 at day 56.

Arm B (Stage I and II)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- Comprehension of informed consent. - 18-45 year old men or women with acknowledged active IDU in the past 90 days and have no travel plans that would interfere with ability to meet the study visit schedule. - In good general health as determined by a participating study physician and results within acceptable ranges for clinical laboratory evaluations as detailed in Appendix A. - Negative for antibodies to hepatitis C virus (anti-HCV). - Negative for HCV RNA. - Negative antibodies to HIV. - Negative for HBsAg. - Able and willing (in the Investigator's opinion) to comply with all study requirements. - Willing to allow the investigators access to their medical records. - Willingness to practice continuous effective contraception from the screening visit through 90 days after the last vaccination (males and females). - Among females, a negative pregnancy test within 24 hours prior to vaccination. - Agreement to refrain from blood donation during the course of the study or after the study. - Provide written informed consent prior to initiation of any study procedures. - Willing to provide contact information for study follow-up activities, including the address, name and contact information of three people who can be contacted to facilitate follow-up compliance.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (5)

University of California San Francisco - Tenderloin Clinical Research Center

San Francisco, California, 94102-4012, United States

Location

UCSF Community Research Center

San Francisco, California, 94102, United States

Location

Zuckerberg San Francisco General Hospital Unit 5B

San Francisco, California, 94110, United States

Location

Johns Hopkins School of Public Health - Wood Clinic

Baltimore, Maryland, 21205-2400, United States

Location

University of New Mexico - Truman Health Services

Albuquerque, New Mexico, 87102, United States

Location

Related Publications (2)

• Page K, Melia MT, Veenhuis RT, Winter M, Rousseau KE, Massaccesi G, Osburn WO, Forman M, Thomas E, Thornton K, Wagner K, Vassilev V, Lin L, Lum PJ, Giudice LC, Stein E, Asher A, Chang S, Gorman R, Ghany MG, Liang TJ, Wierzbicki MR, Scarselli E, Nicosia A, Folgori A, Capone S, Cox AL. Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection. N Engl J Med. 2021 Feb 11;384(6):541-549. doi: 10.1056/NEJMoa2023345.

  PMID: 33567193 DERIVED

• Salinas E, Boisvert M, Upadhyay AA, Bedard N, Nelson SA, Bruneau J, Derdeyn CA, Marcotrigiano J, Evans MJ, Bosinger SE, Shoukry NH, Grakoui A. Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion. J Clin Invest. 2021 Jan 19;131(2):e140590. doi: 10.1172/JCI140590.

  PMID: 33463551 DERIVED

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Kimberly Page, Ph.D., M.P.H. and Andrea Cox, M.D., Ph.D.
• Organization: University of New Mexico and Johns Hopkins University

pagek@salud.unm.edu, acox@jhmi.edu

505-272-2520, 410-502-2715

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2011
• First Posted: September 19, 2011
• Study Start: March 6, 2012
• Primary Completion: May 25, 2018
• Study Completion: May 25, 2018
• Last Updated: November 19, 2019
• Results First Posted: July 22, 2019

Record last verified: 2017-04-05

Locations

US (5)