Yellow Fever Vaccine on Statin/ Non Statin Subjects

NCT03116802 | Completed Phase 2

• 1 other identifier: YF-Statin-01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Since the 1st pandemic of the 21st century caused by SARS coronavirus, the world has experienced outbreaks of swine origin H1N1 influenza, Ebola and Zika viruses, which have all resulted in global health crises. Rapid mass vaccination with an effective vaccine such as a live attenuated vaccine, of vulnerable immune-naïve populations to establish herd immunity is an approach to control outbreaks. Such live attenuated vaccine had been used with great success in sporadic yellow fever outbreaks and recently successfully employed in Ebola field trial, both of these diseases have the potential for pandemic spread. Indeed, live attenuated vaccines have proven especially effective in controlling childhood diseases and have even succeeded in eradicating polio and measles from most parts of the world. However, deployment of such vaccines for pandemic control cannot be limited to children but must include adults in order to rapidly elevate herd immunity rates to halt transmission. Vaccinating adults may produce efficacy rates significantly different to those observed in children due to the prevalence of chronic diseases and their associated metabolic complications. Presently, there are 1 billion people who are overweight, many suffer from concurrent metabolic disorders. As activation of the adaptive immunity is reliant on a robust innate immune response to vaccines, metabolic disorders and long-term anti-inflammatory therapy with interventions such as statins may reduce vaccine immunogenicity resulting in suboptimal efficacy in this subpopulation. This study would therefore test the hypothesis that statins reduce live attenuated vaccine immunogenicity. We will combine a clinical trial with systems vaccinology approaches to define the impact statins has on the innate immune, B and T-cell responses to live attenuated vaccination. Our study will thus extend upon another recently completed trial by us and will provide new insights into the determinants of vaccine efficacy in a rapidly growing and aging population globally

Conditions

Yellow Fever Vaccine; Yellow Fever

Outcome Measures

Primary Outcomes (1)

• the adaptive immune response to YF vaccination in (A): Adult human volunteers who are on long term statins therapy and (B): Adult human volunteers (controls)

  the difference in neutralizing antibody titer to YF17D at Day 28, as measured by plaque reduction neutralization test (PRNT)

  28 days

Secondary Outcomes (2)

• the difference in innate immune response to YF vaccination in adult human volunteers on long term statins therapy compared to controls post-YF vaccination

  28 days

• the cellular immune response of adult human volunteers on long term statins therapy with controls following YF vaccination.

  28 days

Study Arms (2)

Statin Group

EXPERIMENTAL

A total of 35 healthy adult subjects, 30-50 years old with a range of BMI from 18 to 30 kg/m2, pre-screened to be receiving long term statin therapy of ≥ 6 months and negative for diabetes (defined as HbA1c \<6.5%) will be enrolled upon written informed consent. They will receive a single dose of 0.5ml of Stamaril (live attenuated yellow fever vaccine)

Drug: Stamaril (live attenuated yellow fever vaccine)

Control Group

ACTIVE COMPARATOR

Another 35 healthy non-diabetic adult subjects, 30-50 years old with a range of BMI from 18 to 30 kg/m2, not receiving long-term statins will serve as controls will be enrolled upon written informed consent. They will receive a single dose of 0.5ml of Stamaril (live attenuated yellow fever vaccine)

Drug: Stamaril (live attenuated yellow fever vaccine)

Interventions

Stamaril (live attenuated yellow fever vaccine) DRUG

They will receive a single dose of 0.5ml of Stamaril (live attenuated yellow fever vaccine)

Control Group; Statin Group

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults, 30-50 years of age at the time of screening.
• Negative for diabetes (defined as HbA1c \<6.5%)
• Range of BMI from 18 to 30kg/m 2
• Statin Group: receiving long term statin therapy (Simvastatin, Atorvastatin and Rosuvastatin) for ≥6 months
• Control group: not receiving long-term statins
• Negative for anti-dengue antibodies by ELISA. Subjects will be screened using a commercially available ELISA (PanBio)
• Subjects who are willing to comply with the requirements of the study protocol and scheduled visits. (e.g., completion of the subject diary, return for follow-up visits) and who are willing to make themselves available for the duration of the study, with access to a consistent means of telephone contact, which may be either at home or at the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device (i.e. a common-use phone serving multiple rooms or apartments).
• Subjects who give written informed consent approved by the Ethical Review Board governing the site.
• Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. The laboratory values must be within the normal range of the assessing site or show abnormalities that are deemed not clinically significant as judged by the investigator. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event.
• Accessible vein at the forearm for blood collection.
• Female subjects of non-child bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Post menopause: subjects must have had at least 12 months of natural (spontaneous) amenorrhea
• Female subjects of childbearing potential may be enrolled in the study if they have negative urine pregnancy tests on the day of screening and day of vaccination
• Both male (if he has a partner of childbearing potential) and female subjects (of childbearing potential) must agree to use adequate and reliable contraceptive measures (eg. Spermicides, condoms, contraceptive pills) or practice abstinence for 10 days after vaccination

You may not qualify if:

• Presence of acute infection in the preceding 7 days or presence of a temperature ≥ 38.0°C (oral or tympanic temperature assessment), or acute symptoms greater than of "mild" severity on the scheduled date of first vaccination.
• History of severe drug and /or food allergies and/or known allergies to the trial product or its components.
• Any condition that, in the opinion of the investigator, would complicate or compromise the study or wellbeing of the subject.
• Woman who is pregnant or breast feeding.
• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, or immunosuppressive disorders that would be a risk factor when administered the Investigational product (IP).
• History of thymus gland disease.
• Diagnosed with cancer or on treatment for cancer within the 3 years prior to the screening.
• Evidence of clinically significant anaemia and other any significant active haematological disease, or having donated \> 450 mL of blood within the past three months.
• Evidence of substance abuse, or previous substance abuse.
• Participation in a study involving administration of an investigational compound within the past four months, or planned participation during the duration of this study.
• Administration of any licensed vaccine within 30 days before the first study vaccine dose.
• Subject who has been vaccinated with YF vaccine previously.

Sponsors & Collaborators

• Singapore General Hospital: lead

Study Sites (1)

SingHealth Investigational Medicine Unit

Singapore, 169608, Singapore

Location

MeSH Terms

Conditions

Yellow Fever

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Jenny Dr Low

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: April 17, 2017
• Study Start: March 8, 2017
• Primary Completion: April 16, 2018
• Study Completion: April 16, 2018
• Last Updated: March 23, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)