RSV001 - A New Vaccine to Prevent Severe Viral Chest Infections.

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by ReiThera Srl
Sponsor:
Information provided by (Responsible Party):
ReiThera Srl
ClinicalTrials.gov Identifier:
NCT01805921
First received: March 5, 2013
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

In this study we are testing a new vaccine against Respiratory Syncytial Virus (RSV).

This virus can cause respiratory infections such as bronchiolitis and pneumonia. It affects all ages, but especially infants, adults with a suppressed immune system, and the elderly. RSV only infects humans and occurs in epidemics each winter. It is the single most common cause of severe respiratory illness in children.

There is no effective anti-viral medication to treat RSV infections. There is a monoclonal antibody, which can be given to 'at-risk' children given by injection on a monthly basis during winter to provide short term protection against infection, but it is only partially effective and prohibitively expensive. Currently, there is no licensed vaccine to prevent RSV infection and there remains a real need to develop a vaccine as a cost-effective method to save lives and reduce the cost of disease caused by RSV.


Condition Intervention Phase
Respiratory Syncytial Virus Infections
Biological: PanAd3-RSV given intra-nasally (high dose)
Biological: MVA-RSV given by intra-muscular injection (high dose)
Biological: PanAd3-RSV given by intra-muscular injection (high dose)
Biological: PanAd3-RSV given intranasally (low dose)
Biological: MVA-RSV given by intra-muscular injection (low dose)
Biological: PanAd3-RSV given by intra-muscular injection (low dose)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase I Study to Assess Safety and Immunogenicity of a New Respiratory Syncytial Virus (RSV) Vaccine Based on the RSV Viral Proteins F, N and M2-1 Encoded by Simian Adenovirus (PanAd3-RSV) and Modified Vaccinia Virus Ankara (MVA-RSV)

Resource links provided by NLM:


Further study details as provided by ReiThera Srl:

Primary Outcome Measures:
  • Safety [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]

    The recording and assessment of local and systemic adverse events following administration of each vaccine dose;

    • Fever
    • Headache
    • Nausea and/or vomiting
    • Malaise
    • Myalgia
    • Arthralgia
    • Injection site adverse events (for IM administered vaccine); pain or tenderness, induration, redness and swelling
    • Nasal site adverse events (for IN administered vaccine); pain or tenderness, irritation and discharge
    • Blood parameters
    • Any unsolicited symptom(s) not listed above


Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

    Immunological assays to study immune responses to each vaccine, including:

    • Serum antibody response to RSV F antigen
    • Serum antibody response capable of RSV neutralization
    • Quantification of circulating vaccine-induced B-cell secreting antibodies (IgA and IgG) against RSV F antigen
    • Quantification of circulating vaccine-induced T-cell responses against RSV antigens F, N and M2-1
    • Any further exploratory immunology to detect vaccine related immune responses


Estimated Enrollment: 70
Study Start Date: May 2013
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1. Prime PanAd3-RSV (IM), boost MVA-RSV (IM)

Group 1A. Low dose prime PanAd3-RSV given by intra-muscular injection (IM) - low dose boost MVA-RSV given by intra-muscular injection (IM). 2 volunteers, 18-50 years. Interval: 8 weeks.

Group 1B. High dose prime PanAd3-RSV given by intra-muscular injection (IM) - high dose boost MVA-RSV given by intra-muscular injection (IM). 8 volunteers, 18-50 years. Interval: 8 weeks.

Biological: MVA-RSV given by intra-muscular injection (high dose)
High dose = 1x10^8 pfu
Biological: PanAd3-RSV given by intra-muscular injection (high dose)
High dose = 5x10^10 vp
Biological: MVA-RSV given by intra-muscular injection (low dose)
Low dose = 1x10^7 pfu
Biological: PanAd3-RSV given by intra-muscular injection (low dose)
Low dose = 5x10^9 vp
Experimental: Arm 2. Prime PanAd3-RSV (IM), boost PanAd3-RSV (IM)

Group 2A. Low dose prime PanAd3-RSV given by intra-muscular injection (IM) - low dose boost PanAd3-RSV given by intra-muscular injection (IM). 2 volunteers, 18-50 years. Interval: 4 weeks.

Group 2B. High dose prime PanAd3-RSV given by intra-muscular injection (IM) - high dose boost PanAd3-RSV given by intra-muscular injection (IM). 8 volunteers, 18-50 years. Interval: 4 weeks.

Biological: PanAd3-RSV given by intra-muscular injection (high dose)
High dose = 5x10^10 vp
Biological: PanAd3-RSV given by intra-muscular injection (low dose)
Low dose = 5x10^9 vp
Experimental: Arm 3. Prime PanAd3-RSV (IN), boost MVA-RSV (IM)

Group 3A. Low dose prime PanAd3-RSV given intra-nasally (IN) - low dose boost MVA-RSV given by intra-muscular injection (IM). 2 volunteers, 18-50 years. Interval: 8 weeks.

Group 3B. High dose prime PanAd3-RSV given intra-nasally (IN) - high dose boost MVA-RSV given by intra-muscular injection (IM). 8 volunteers, 18-50 years. Interval: 8 weeks.

Biological: PanAd3-RSV given intra-nasally (high dose)
High dose = 5x10^10 vp
Biological: MVA-RSV given by intra-muscular injection (high dose)
High dose = 1x10^8 pfu
Biological: PanAd3-RSV given intranasally (low dose)
Low dose = 5x10^9 vp
Biological: MVA-RSV given by intra-muscular injection (low dose)
Low dose = 1x10^7 pfu
Experimental: Arm 4. Prime PanAd3-RSV (IN), boost PanAd3-RSV (IM)

Group 4A. Low dose prime PanAd3-RSV given intra-nasally (IN) - low dose boost PanAd3-RSV given by intra-muscular injection (IM). 2 volunteers, 18-50 years. Interval: 8 weeks.

Group 4B. High dose prime PanAd3-RSV given intra-nasally (IN) - high dose boost PanAd3-RSV given by intra-muscular injection (IM). 8 volunteers, 18-50 years. Interval: 8 weeks.

Biological: PanAd3-RSV given intra-nasally (high dose)
High dose = 5x10^10 vp
Biological: PanAd3-RSV given by intra-muscular injection (high dose)
High dose = 5x10^10 vp
Biological: PanAd3-RSV given intranasally (low dose)
Low dose = 5x10^9 vp
Biological: PanAd3-RSV given by intra-muscular injection (low dose)
Low dose = 5x10^9 vp
No Intervention: Arm 5. No vaccine
Group 5. Non-vaccinated control group. 6 volunteers, 60-75 years.
Experimental: Arm 6. MVA-RSV (IM)
Group 6. Single high dose MVA-RSV given by intra-muscular injection (IM). 6 volunteers, 60-75 years.
Biological: MVA-RSV given by intra-muscular injection (high dose)
High dose = 1x10^8 pfu
Experimental: Arm 7. Prime PanAd3-RSV (IM), boost PanAd3-RSV (IM)
Group 7. High dose prime PanAd3-RSV given by intra-muscular injection (IM) - high dose boost PanAd3-RSV given by intra-muscular injection (IM). 6 volunteers, 60-75 years. Interval: 4 weeks.
Biological: PanAd3-RSV given by intra-muscular injection (high dose)
High dose = 5x10^10 vp
Experimental: Arm 8. Prime PanAd3-RSV (IN), boost MVA-RSV (IM)
Group 8. High dose prime PanAd3-RSV given intra-nasally - high dose boost MVA-RSV given by intra-muscular injection (IM). 6 volunteers, 60-75 years. Interval: 8 weeks.
Biological: PanAd3-RSV given intra-nasally (high dose)
High dose = 5x10^10 vp
Biological: MVA-RSV given by intra-muscular injection (high dose)
High dose = 1x10^8 pfu
Experimental: Arm 9. Prime PanAd3-RSV (IM), boost MVA-RSV (IM)
Group 9. High dose prime PanAd3-RSV given by intra-muscular injection (IM) - high dose boost MVA-RSV given by intra-muscular injection (IM). 6 volunteers, 60-75 years. Interval: 8 weeks.
Biological: MVA-RSV given by intra-muscular injection (high dose)
High dose = 1x10^8 pfu
Biological: PanAd3-RSV given by intra-muscular injection (high dose)
High dose = 5x10^10 vp

Detailed Description:

We are testing two new RSV vaccines, given in different combinations and by different routes of administration. Each vaccine uses the same RSV proteins to stimulate immune responses. These proteins are the F (Fusion), N (Nucleocapsid) and M2-1 (Matrix) proteins. The F protein sits on the surface of the virus and is needed to infect human cells. Antibodies to this protein are an important mechanism to prevent infection. The N and M2-1 proteins are needed for viral replication and are targets of immune recognition.

The two vaccines in this study contain all three of these proteins. However, they are delivered into the body using different 'vectors', which are harmless carrier viruses. In this study, we have employed two different vectors:a simian adenoviruses (PanAd3) and Modified Vaccinia virus Ankara (MVA).

We administer these vaccines using a 'prime-boost' strategy, in which one of these vaccines is used to 'prime' the immune system, which is then 'boosted' 4 or 8 weeks later, depending on the groups, by administration of an alternative vaccine or the same vaccine given by a different route.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Participants must satisfy all of the following criteria to be considered eligible for the study:

  • Willing and able to give informed consent for participation in the study
  • Aged between 18 and 50 years (Groups 1-4) or aged 60-75 years (Groups 5-9)
  • In good health as determined by

    • Medical history
    • Physical examination
    • Clinical judgment of the investigators
  • Willing to use effective contraception

    • Females: The oral contraceptive pill, contraceptive implant or barrier methods from one month prior and for the duration of the study (Groups 1-4 only)
    • Males: Barrier contraception from V1 until 3 months after the last vaccination
  • Able to attend the scheduled visits and to comply with all study procedures
  • Willing to allow his or her General Practitioner and/or Consultant, if appropriate, to be notified of participation in the study
  • Confirmation from GP that they are aware of the inclusion and exclusion criteria and are satisfied from their knowledge of the volunteer that they are suitable to enroll
  • Willing to provide their National Insurance/Passport number for the purpose of TOPS registration

Exclusion Criteria:

The participant may not enter the study if any of the following apply:

  • History of significant organ/system disease that could interfere with trial conduct or completion. This includes any history of significant disease in the following;

    • Cardiovascular disease including congenital heart disease, previous myocardial infarction, valvular heart disease (or history of rheumatic fever), previous bacterial endocarditis, history of cardiac surgery (including pacemaker insertion), personal or family history of cardiomyopathy or sudden adult death
    • Respiratory disease such as asthma (excluding childhood asthma not treated in adulthood) and chronic obstructive pulmonary disease
    • Endocrine disorders such as diabetes mellitus and Addison's disease
    • Significant renal or bladder disease, including history of renal calculi
    • Biliary tract disease
    • Gastro-intestinal disease such as inflammatory bowel disease, abdominal surgery within the last two years, coeliac disease and liver disease
    • Neurological disease such as seizures and myasthenia gravis
    • Metabolic disease such as glucose-6-phosphate dehydrogenase deficiency
    • Psychiatric illness requiring hospitalization or depression whose severity is deemed clinical significant by the Chief Investigator, Consultant or GP
    • Non-benign cancer, including squamous cell carcinoma, basal cell carcinoma of the skin and cervical carcinoma in situ
    • Clinically significant contact dermatitis
  • Have any known or suspected impairment or alteration of immune function, resulting from, for example:

    • Congenital or acquired immunodeficiency
    • Human Immunodeficiency Virus infection or symptoms/signs suggestive of an HIV-associated condition
    • Autoimmune disease
    • Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid therapy
    • Receipt of immunoglobulin or any blood product transfusion within 3 months of study start
  • A vaccination history indicative of;

    • Planning to receive any vaccine other than the study vaccine within 4 weeks following vaccination
    • A history of anaphylaxis reaction to a vaccine
    • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. Kathon
    • Previously having received a recombinant simian or human adenoviral vaccine
    • Previously having received a recombinant MVA vaccine
  • Detection of any of the following at screening

    • IgA deficiency
    • Anti-HIV antibody
    • Hepatitis B surface antigen
    • Anti-HCV antibody
    • Any other significant abnormalities on screening investigations at the discretion of an Investigator
  • Known or suspected drug and/or alcohol misuse (alcohol misuse defined as an intake exceeding 42 units per week)
  • Nasal septal pathology including

    • Congenital deformities such as an abnormal septum or polyps
    • Previous cauterization, rhinoplasty or surgery of any kind
    • Recurrent epistaxis
  • Scheduled procedures requiring general anaesthesia during the study
  • Participation in another research study involving an investigational product in the past 12 weeks, or are planning to do so within the 20 weeks of this study
  • Inability, in the opinion of the Investigator, to comply with all study requirements
  • Female participants who are pregnant, lactating or planning pregnancy during the course of the study
  • Has donated blood within 4 months before starting the trial, or is intending to donate blood during the trial and up to 12 weeks after completing the study
  • Any other significant disease or disorder which, in the opinion of the Investigator, may

    • Put the participants at risk because of participation in the study
    • Influence the result of the study
    • Impair the participant's ability to participate in the study
  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: NCT01805921

Contacts
Contact: Andrew J Pollard, PhD 01865 857420 andrew.pollard@paediatrics.ox.ac.uk
Contact: Christopher A Green, MRCP(UK) 01865 857420 christopher.green@paediatrics.ox.ac.uk

Locations
United Kingdom
Centre for Clinical Vaccinology & Tropical Medicine (CCVTM) Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 7LE
Contact: Christopher A Green, MRCP(UK)    01865 857420    christopher.green@paediatrics.ox.ac.uk   
Contact: Zoe Stevens    01865 857420    zoe.stevens@paediatrics.ox.ac.uk   
Principal Investigator: Andrew J Pollard, PhD         
Sponsors and Collaborators
ReiThera Srl
Investigators
Principal Investigator: Andrew J Pollard, FRCPCH PhD University of Oxford. Department of Paediatrics
  More Information

Additional Information:
No publications provided

Responsible Party: ReiThera Srl
ClinicalTrials.gov Identifier: NCT01805921     History of Changes
Other Study ID Numbers: RSV001, 2011-003589-34
Study First Received: March 5, 2013
Last Updated: September 2, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Keywords provided by ReiThera Srl:
Respiratory Syncytial Virus
RSV
Vaccine

Additional relevant MeSH terms:
Communicable Diseases
Infection
Respiratory Syncytial Virus Infections
Virus Diseases
Mononegavirales Infections
Paramyxoviridae Infections
Pneumovirus Infections
RNA Virus Infections

ClinicalTrials.gov processed this record on October 20, 2014