Hepatitis CPhase 1/2NCT01436357

Staged Phase I/II Hepatitis C Prophylactic Vaccine

A Phase 1/2 study testing AdCh3NSmut1 and MVA-NSmut in people with Hepatitis C, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Hepatitis C
What is being tested?: AdCh3NSmut1 and MVA-NSmut
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 548 participants
Where: 5 sitesUnited States
Study dates: 6 Mar 2012to 25 May 2018
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

The subject is currently participating in a study that involves an experimental agent (vaccine, drug, biologic device, blood product, or medication) or has received an experimental agent within 30 days prior to enrollment in this study, or expects to receive another experimental agent during participation in this study. - Prior receipt of a recombinant simian or human adenoviral vaccine or MVA vaccine. - Administration of immunoglobulins and/or any blood products within the 90 days preceding the planned administration of the vaccine candidate. - Any confirmed or suspected immunosuppressive or immunodeficient state, including: HIV infection; asplenia; recurrent, severe infections. - History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (i.e., known hypersensitivity to aminoglycosideantibiotics or to egg proteins). - History of clinically significant contact dermatitis or other significant dermatological conditions such as psoriasis. - Any history of anaphylaxis in reaction to vaccination. - Pregnancy, lactation or willingness/intention to become pregnant during the study. - History of cancer (except for successfully treated basal cell carcinoma of the skin and cervical carcinoma in situ). - History of severe psychiatric illness, including severe depression, history of suicidal ideation, suicidal attempts, or psychosis requiring medication. The subject has a diagnosis of schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis that is uncontrolled and would interfere with the ability to adhere to the protocol. - Any other serious chronic illness requiring hospital specialist supervision. - Suspected or known current alcohol abuse as defined by a score of 10 or more on the Alcohol Use Disorders Identification Test (AUDIT) C test (a standardized screening tool used to identify hazardous drinkers or those with active alcohol use disorders, including abuse or dependence). - At high risk of HIV infection by the following criteria (adapted from HIV Network for Prevention Trials (HIVNET) behavioral criteria for high risk of HIV): (1) sexually active male who has sex with men (MSM), defined as (i) male who has had anal sex with male sexual partner or partners in the past year or (ii) a male who exchanged sex with male partner(s) for money or drugs in the past year; and (2) female and in a current relationship with a high risk male (active MSM, HIV positive male). - Any other significant disease, disorder or finding, which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the result of the study, or may influence the subject's ability to participate in the study. - History of or current diagnosis of Diabetes mellitus. - History of or current diagnosis of autoimmune disease. - History of or current cardiac disease including history of myocardial infarction or arrhythmia. - Current diagnosis of active liver disease. - History of seizure disorder or currently taking anti-convulsant therapy that would interfere with safety evaluation. - Uncontrolled hypertension (defined as systolic blood pressure being greater than 140mm Hg or diastolic blood pressure being greater than 90mm Hg). - History of splenectomy. - Long term immunosuppressive use (defined as taken for 14 days or more in total at any time during the past 180 days) of high dose oral or parenteral glucocorticoids (high dose defined as prednisone >/=20 mg total daily dose, or equivalent dose of other glucocorticoids); or high-dose inhaled steroids (high dose defined as >800 mcg/day of beclomethasone dipropionate or equ ivalent); or any use of hepatotoxic or non-FDA approved medication. - Have an acute illness, including an oral temperature greater than or equal to 100.4 degrees Fahrenheit, within 7 days prior to the first vaccination. - Immunization against another pathogen within 14 days of planned injection. Second vaccination exclusion criteria: The following events associated with vaccine immunization constitute absolute contraindications to further administration of vaccine. The subject will not receive additional vaccination, but will continue with scheduled follow-up procedures except vaccination. 1. Anaphylactic reaction following administration of vaccine. 2. Pregnancy. If a woman reports having a positive home urine pregnancy test or a positive in clinic urine pregnancy test prior to a scheduled second vaccination, she is not eligible to receive the study vaccine. If she later returns to clinic and reports having a negative home urine pregnancy test and this is confirmed by a negative in clinic urine pregnancy test and a negative blood pregnancy test she may be eligible for the second vaccination if she is still within the vaccination window and no other exclusion criteria are met. The following adverse events constitute contraindications to administration of vaccine at that point in time. If any one of these adverse events occurs at the time scheduled for vaccination, the subject may be vaccinated at a later date (within 28 days of scheduled administration) or withdrawn at the discretion of the investigator. The subject will not receive additional vaccination, but will continue with all scheduled follow-up procedures except vaccination. 3. Acute disease at the time of vaccination (acute disease is defined as the presence of a moderate or severe illness with or without fever). The vaccine dose can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., temperature of <38°C (100.4°F). 4. Temperature of >38°C (100.4°F) at the time of vaccination. 5. Immunization against another pathogen within 14 days of vaccination

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

University of New Mexico - Truman Health Services
Albuquerque, New Mexico, 87102
Johns Hopkins School of Public Health - Wood Clinic
Baltimore, Maryland, 21205-2400
University of California San Francisco - Tenderloin Clinical Research Center
San Francisco, California, 94102-4012
UCSF Community Research Center
San Francisco, California, 94102
Zuckerberg San Francisco General Hospital Unit 5B
San Francisco, California, 94110

Other trials in United States

About this study

Official title: A Staged Phase I/II Study, to Assess Safety, Efficacy and Immunogenicity of a New Hepatitis C Prophylactic Vaccine Based on Sequential Use of AdCh3NSmut1 and MVA-NSmut

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).

Read the detailed description

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. In this clinical trial AdCh3NSmut1 and MVA-NSMut HCV vaccine will be administered intramuscularly to 68 (+/-4) evaluable volunteers in stage 1. A planned interim analysis of safety and immunogenicity will be conducted based on data through 1 week after receipt of the second vaccination. If no safety signal is detected and there is evidence of a measurable immune response to HCV then an additional 472 (+/-4) volunteers will be enrolled in stage 2. The primary objectives of this study will be 1) to assess the safety of the new candidate hepatitis C virus vaccines, AdCh3NSmut1 and MVA-NSmut, compared to placebo when administered to HCV-uninfected injection drug users (IDUs) and 2) to determine if AdCh3NSmut1 and MVA-NSmut HCV vaccines will reduce incidence of chronic HCV infection compared to placebo among HCV-uninfected IDUs. The secondary objective of this study will be to evaluate the immunogenicity of the new candidate hepatitis C virus vaccines, AdCh3NSmut1 and MVA-NSmut, compared to placebo when administered to HCV-uninfected IDUs.The planned duration of the study is approximately 63 months total including accrual time for subjects (assuming 31 months of screening/enrollments, plus 3 months of halted enrollment for the first interim analysis), 2 months vaccination, 18 months follow-up of each enrolled subject, and 9 months extended observation (monthly), from the time of infection, for subjects becoming viremic in the last month of follow-up.

Conditions: Hepatitis C
Being tested: AdCh3NSmut1, MVA-NSmut, Placebo
Keywords: AdCh3NSmut1, Hepatitis C, MVA-NSmut, vaccine
Medical subject headings: Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AdCh3NSmut1Biological
Stages I and II: Receive AdCh3NSmut1 at 2.5 x 10^10 total virus particles (vp)/dose, intramuscularly on day 0.
MVA-NSmutBiological
Stages I and II: 1 dose of MVA-NSmut at the dosage 1.8 x10^8 plaque forming units (pfu) intramuscularly on day 56.
PlaceboOther
Stages I and II: Two doses of placebo intramuscularly, 1 at day 0 and 1 at day 56.

Study groups in NCT01436357
Study group	Role	What they receive
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. Receives: 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. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 7 days after second vaccination

Secondary outcomes (1)

Number of Participants With Positive Cell Mediated Immune Response
Cell mediated immune response was measured by interferon gamma (IFN-gamma) production by T-cells against each of the six HCV genotype 1b peptide pools in the vaccine. Positivity was defined as i) more than 48 spot forming cells per million PBMC; and ii) at least three times the mean background spots per million PBMC found in ELISpot wells containing cells and peptide diluent (DMSO). A participant was considered a responder if a positive response to at least one in 6 mixtures (pools) of peptides was detected.
Measured: Within 14 days after the last vaccination (Day 56)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Mar 201225 May 2018

First posted19 Sep 2011 (estimated)
Study start6 Mar 2012
Primary completion25 May 2018
Study completion25 May 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Hepatitis CStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
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: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 548 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01436357
Sponsor's protocol ID: 10-0069
Status last verified: 5 Apr 2017
First submitted: 15 Sep 2011
Last updated: 19 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 33567193
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.
PubMed 33463551

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Hepatitis C trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Staged Phase I/II Study, to Assess Safety, Efficacy and Immunogenicity of a New Hepatitis C Prophylactic Vaccine Based on Sequential Use of AdCh3NSmut1 and MVA-NSmut
ClinicalTrials.gov ID: NCT01436357
Acronym / sponsor ID: 10-0069
Conditions: Hepatitis C
Keywords: AdCh3NSmut1, Hepatitis C, MVA-NSmut, vaccine
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 548 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: 6 Mar 2012 (actual)
Primary completion: 25 May 2018 (actual)
Study completion: 25 May 2018 (actual)
First posted: 19 Sep 2011 (estimated)
Results: Posted 22 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Arm A (Stage I and II)	Experimental	Biological: AdCh3NSmut1, Biological: MVA-NSmutReceive 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.
Arm B (Stage I and II)	Placebo comparator	Other: PlaceboTwo 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.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

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.

Key exclusion criteria (1 listed)

The subject is currently participating in a study that involves an experimental agent (vaccine, drug, biologic device, blood product, or medication) or has received an experimental agent within 30 days prior to enrollment in this study, or expects to receive another experimental agent during participation in this study. - Prior receipt of a recombinant simian or human adenoviral vaccine or MVA vaccine. - Administration of immunoglobulins and/or any blood products within the 90 days preceding the planned administration of the vaccine candidate. - Any confirmed or suspected immunosuppressive or immunodeficient state, including: HIV infection; asplenia; recurrent, severe infections. - History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (i.e., known hypersensitivity to aminoglycosideantibiotics or to egg proteins). - History of clinically significant contact dermatitis or other significant dermatological conditions such as psoriasis. - Any history of anaphylaxis in reaction to vaccination. - Pregnancy, lactation or willingness/intention to become pregnant during the study. - History of cancer (except for successfully treated basal cell carcinoma of the skin and cervical carcinoma in situ). - History of severe psychiatric illness, including severe depression, history of suicidal ideation, suicidal attempts, or psychosis requiring medication. The subject has a diagnosis of schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis that is uncontrolled and would interfere with the ability to adhere to the protocol. - Any other serious chronic illness requiring hospital specialist supervision. - Suspected or known current alcohol abuse as defined by a score of 10 or more on the Alcohol Use Disorders Identification Test (AUDIT) C test (a standardized screening tool used to identify hazardous drinkers or those with active alcohol use disorders, including abuse or dependence). - At high risk of HIV infection by the following criteria (adapted from HIV Network for Prevention Trials (HIVNET) behavioral criteria for high risk of HIV): (1) sexually active male who has sex with men (MSM), defined as (i) male who has had anal sex with male sexual partner or partners in the past year or (ii) a male who exchanged sex with male partner(s) for money or drugs in the past year; and (2) female and in a current relationship with a high risk male (active MSM, HIV positive male). - Any other significant disease, disorder or finding, which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the result of the study, or may influence the subject's ability to participate in the study. - History of or current diagnosis of Diabetes mellitus. - History of or current diagnosis of autoimmune disease. - History of or current cardiac disease including history of myocardial infarction or arrhythmia. - Current diagnosis of active liver disease. - History of seizure disorder or currently taking anti-convulsant therapy that would interfere with safety evaluation. - Uncontrolled hypertension (defined as systolic blood pressure being greater than 140mm Hg or diastolic blood pressure being greater than 90mm Hg). - History of splenectomy. - Long term immunosuppressive use (defined as taken for 14 days or more in total at any time during the past 180 days) of high dose oral or parenteral glucocorticoids (high dose defined as prednisone >/=20 mg total daily dose, or equivalent dose of other glucocorticoids); or high-dose inhaled steroids (high dose defined as >800 mcg/day of beclomethasone dipropionate or equ ivalent); or any use of hepatotoxic or non-FDA approved medication. - Have an acute illness, including an oral temperature greater than or equal to 100.4 degrees Fahrenheit, within 7 days prior to the first vaccination. - Immunization against another pathogen within 14 days of planned injection. Second vaccination exclusion criteria: The following events associated with vaccine immunization constitute absolute contraindications to further administration of vaccine. The subject will not receive additional vaccination, but will continue with scheduled follow-up procedures except vaccination. 1. Anaphylactic reaction following administration of vaccine. 2. Pregnancy. If a woman reports having a positive home urine pregnancy test or a positive in clinic urine pregnancy test prior to a scheduled second vaccination, she is not eligible to receive the study vaccine. If she later returns to clinic and reports having a negative home urine pregnancy test and this is confirmed by a negative in clinic urine pregnancy test and a negative blood pregnancy test she may be eligible for the second vaccination if she is still within the vaccination window and no other exclusion criteria are met. The following adverse events constitute contraindications to administration of vaccine at that point in time. If any one of these adverse events occurs at the time scheduled for vaccination, the subject may be vaccinated at a later date (within 28 days of scheduled administration) or withdrawn at the discretion of the investigator. The subject will not receive additional vaccination, but will continue with all scheduled follow-up procedures except vaccination. 3. Acute disease at the time of vaccination (acute disease is defined as the presence of a moderate or severe illness with or without fever). The vaccine dose can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., temperature of <38°C (100.4°F). 4. Temperature of >38°C (100.4°F) at the time of vaccination. 5. Immunization against another pathogen within 14 days of vaccination

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
AdCh3NSmut1Stages I and II: Receive AdCh3NSmut1 at 2.5 x 10^10 total virus particles (vp)/dose, intramuscularly on day 0.	Biological	Arm A (Stage I and II)
MVA-NSmutStages I and II: 1 dose of MVA-NSmut at the dosage 1.8 x10^8 plaque forming units (pfu) intramuscularly on day 56.	Biological	Arm A (Stage I and II)
PlaceboStages I and II: Two doses of placebo intramuscularly, 1 at day 0 and 1 at day 56.	Other	Arm B (Stage I and II)

Primary outcome

Number of Participants With Chronic Hepatitis C Virus (HCV) Infection at 6 Months
Time frame: 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.
Number of Participants With Clinical Safety Laboratory Adverse Events (AEs) at 1 Month After First Vaccination
Time frame: 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.
Number of Participants With Clinical Safety Laboratory Adverse Events (AEs) at 1 Month After Second Vaccination
Time frame: 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.
Number of Participants With Severe Local and/or Systemic Solicited Reactogenicity Signs and Symptoms in the 8 Days (Day 0-7) After First Vaccination
Time frame: 7 days 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.
Occurrence of Vaccine-related Serious Adverse Events (SAEs) From the Time of First Vaccination Through the Entire Study Period
Time frame: Day 0 to 29 months
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.
Number of Participants With Severe Local and/or Systemic Solicited Reactogenicity Signs and Symptoms in the 8 Days (Day 0-7) After Second Vaccination
Time frame: 7 days 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.

1 secondary outcome

Number of Participants With Positive Cell Mediated Immune Response
Time frame: Within 14 days after the last vaccination (Day 56)

Results and safety

Results posted to the registry on 22 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AdCh3NSmut1 and MVA-NSmut	274	152
Sodium Chloride Placebo	274	146

Primary outcome: Number of Participants With Chronic Hepatitis C Virus (HCV) Infection at 6 Months

Time frame: 6 months. Count of participants. Unit: Participants

Measure	AdCh3NSmut1 and MVA-NSmut n = 275	Sodium Chloride Placebo n = 273
Value	14	14

AdCh3NSmut1 and MVA-NSmut vs Sodium Chloride Placebo: Hazard Ratio (HR): 1.529 (95% CI 0.661 to 3.535), p = 0.317, Regression, Cox

Population analysed: All randomized are included as treated (one participant randomized to placebo received vaccine) with the following censoring criteria applied: did not receive both vaccinations, HCV infected at baseline, did not have sufficient follow-up to be evaluable for efficacy, or had major protocol deviations compromising the assessment of vaccine efficacy.

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

Time frame: 1 month after first vaccination. Count of participants. Unit: Participants

Measure	AdCh3NSmut1 and MVA-NSmut n = 274	Sodium Chloride Placebo n = 272
Value	70	48

AdCh3NSmut1 and MVA-NSmut vs Sodium Chloride Placebo: Risk Difference (RD): 0.08 (95% CI -0.01 to 0.16), p = 0.029, Fisher Exact

Population analysed: The safety analysis population includes all participants with blood collected at the timepoint summarized. Participants are analyzed as treated.

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

Time frame: 1 month after second vaccination. Count of participants. Unit: Participants

Measure	AdCh3NSmut1 and MVA-NSmut n = 228	Sodium Chloride Placebo n = 227
Value	73	49

AdCh3NSmut1 and MVA-NSmut vs Sodium Chloride Placebo: Risk Difference (RD): 0.10 (95% CI 0.01 to 0.20), p = 0.015, Fisher Exact

Population analysed: The safety analysis population includes all participants with blood collected at the timepoint summarized. Participants are analyzed as treated.

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

Time frame: 7 days after first vaccination. Count of participants. Unit: Participants

Measure	AdCh3NSmut1 and MVA-NSmut n = 274	Sodium Chloride Placebo n = 272
Value	0	0

AdCh3NSmut1 and MVA-NSmut vs Sodium Chloride Placebo: Risk Difference (RD): 0.0, p = 0.00, Fisher Exact

Population analysed: The safety analysis population includes all participants receiving the vaccination for whom data were available. Participants are analyzed as treated.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Solicited reactogenicity symptoms were collected before vaccination, and then daily for 8 days post-vaccination (Day 0-7) after each vaccination on a memory aid. Unsolicited adverse events were collected through Day 90. At visits following Day 90 up to Day 140, only SAE's were collected.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AdCh3NSmut1 and MVA-NSmut	40 of 274 (14.6%)	229 of 274 (83.6%)	5 of 274
Sodium Chloride Placebo	25 of 272 (9.2%)	172 of 272 (63.2%)	2 of 272

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33567193Page 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.
Derived from this study: PubMed 33463551Salinas 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.

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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.

The record lists no contact. Use the official record to reach the sponsor.

5 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 AdCh3NSmut1 and MVA-NSmut in people with Hepatitis C, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 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 1 inclusion and 1 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 19 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 22 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Chronic Hepatitis C Virus (HCV) Infection at 6 Months (time frame: 6 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01436357, which also lists 2 linked publications.

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 19 Nov 2019.