Healthy volunteers Infections and Infestations
Conditions
Interventions
This is a single-blinded, randomised Phase I trial using the online tool “Sealed Envelope” to generate randomisation lists. Healthy participants aged 18 to 50 years will be enrolled at a single centre
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Inclusion criteria
Inclusion criteria: 1. Healthy adults, aged 18-50 years on the day of screening 2. Willing and able to provide written informed consent 3. If female and of childbearing potential, willing to use a highly effective method of contraception from screening until 18 weeks after last injection 4. If male and not sterilised, willing to avoid impregnating female partners from screening until 18 weeks after last injection 5. Willing to avoid all other vaccines from within 4 weeks before and after the first and second injection 6. Willing and able to comply with visit schedule, complete online diaries and provide samples 7. Willing to abstain from donating blood for three months after the end of their participation in the trial or longer, if necessary 8. Willing to grant authorised persons access to his/her trial-related medical record and GP records either directly or indirectly i A woman will be considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as no menses for 18 months without an alternative medical cause. ii The following methods are considered highly effective: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation – oral, intravaginal or transdermal; • progestogen-only hormonal contraception associated with inhibition of ovulation – oral, injectable or implantable • intrauterine device (IUD); • intrauterine hormone-releasing system (IUS); • bilateral tubal occlusion; • vasectomised partner, where the vasectomised partner has received medical assessment of the surgical success; and • sexual abstinence, defined as refraining from heterosexual intercourse – must be the preferred and usual lifestyle of the participant. iii Nonclinical studies of saRNAs showed maximal expression of the vaccine immunogen at 7 days post-immunisation, approaching baseline by 3 weeks post-immunisation, with some residual very low expression seen out to 9 weeks. Biodistribution studies with LNP-MARVsaRNA, LNP-EBOVsaRNA and LNP-LASSAsaRNA are planned, but in the absence of data we wish to take a conservative approach to the contraception period and require an 18-week washout period. iv Through the use of condoms or sexual abstinence It is recommended that participants have an up to date vaccination status for any required immunisations.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating 2. Has a significant clinical history, physical finding on clinical examination during screening, or presence of a disease that is active or requires treatment to control it, including cardiac, respiratory, endocrine, metabolic, autoimmune, liver, neurological, oncological, psychiatric, immunosuppresive/immunodeficient or other disorders which in the opinion of the investigator is not compatible with healthy status, may compromise the volunteer’s safety, preclude vaccination or compromise interpretation of the immune response to vaccine. Individuals with mild/moderate, well-controlled comorbidities are allowed. 3. History of Marburg virus, Ebola virus and/or Lassa virus infection 4. History of anaphylaxis or angioedema 5. History of severe or multiple allergies to drugs or pharmaceutical agents 6. History of severe local or general reaction to vaccination defined as: a. local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours b. general: fever =39.5 °C within 48 hours; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours Ever received an experimental or authorised vaccine against Ebola, Marburg, or Lassa fever viruses 7. Receipt of any immunosuppressive agents within 18 weeks of screening by any route other than topical 8. Detection of antibodies to hepatitis C 9. Detection of antibodies to HIV 10. Grade 1i and above abnormalities in routine laboratory parameters (see Table 4) using the FDA toxicity table Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, taking account of local laboratory reference ranges. https://www.fda.gov/media/73679/download Participating in another clinical trial with an investigational drug or device or treated with an investigational drug within 28 days of screening. 11. Has received an immunisation within 28 days of screening i Trace of protein and/or blood on dipstick urinalysis and ALT/AST =1.2 x ULN are not exclusion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Solicited local injection site reactions starting within 7 days of administration of the vaccine: pain, tenderness, erythema, swelling. These will be measured using a participant diary card. 2.Solicited systemic reactions starting within 7 days of administration of the vaccine: pyrexia, fatigue, myalgia, headache, chills, arthralgia. These will be measured using a participant diary card. 3.Unsolicited adverse reactions (ARs) throughout the trial period (including serious ARs). 4.Serious Adverse Events throughout the trial period. 5.Unsolicited adverse events throughout the trial period. 6.The titre of vaccine-induced serum IgG binding antibody responses to the Marburg virus, Ebola virus and Lassa virus fever virus surface glycoproteins 2 weeks after the second vaccinations (day 98). Antigen-specific IgG antibody concentrations in participant sera will be measured in ng/mL using validated ELISA. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Cell-mediated vaccine-induced immune responses measured by T and B cell ELISpot in participants using PBMC taken on days 0, 28, 84 and 98 (T cells) or 112 (B cells). 2. Cell-mediated vaccine-induced immune responses measured by flow cytometry and intracellular cytokine staining using PBMC taken on days 0, 28, 84 and 98. 3. Serum neutralising antibodies in a Marburg, Ebola or Lassa pseudovirus-based neutralisation assay using sera taken on days 0, 28, 84, 98 and 112. 4. The profile of class and sub-class of antibody response will be measured in ng/mL using antigen-specific IgG (1-4) and IgA antibody validated ELISA on days 0, 28, 84, 98 and 112. 5. Serum markers of innate immune response measured by MSD assay in participant plasma on days 1 and 85. 6. Purification of antigen-specific B cells to isolate neutralising monoclonal antibodies to enhance understanding of targeted epitopes. B cells will be isolated from participant PBMC taken on day 112. | — |
Countries
England, United Kingdom
Contacts
Public ContactMarta Boffito
Outcome results
None listed