Solidarity/Tokomeza Ebola Trial

NCT05909358 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TOKOMEZA PLUS
• Study Type: interventional
• Target: 2,121
• Locations: 0 countries
• Sites: N/A

Brief Summary

The TokomezaPlus Ebola trial is a phase I/II double blind randomised clinical trial designed to assess the safety and immunogenicity of candidate SUDV vaccines in Uganda during the inter outbreak period. Uganda is prone to Ebola virus disease outbreaks especially those caused by the Ebola Sudan (SUDV) species. TokomezaPlus Ebola Vaccine trial protocol has two main components: a) Safety b) Immunogenicity and is designed to create a living protocol that will be used to study the safety and immunogenicity of SUDV-candidate vaccines in the East African EVD-prone countries.

Conditions

Sudan Ebola Virus Vaccines

Outcome Measures

Primary Outcomes (4)

• Incidence of solicited, unsolicited adverse and serious adverse events (safety)

  The adverse events (AE) and serious adverse events (SAE) will be evaluated to determine the link to the investigational product. They will then be classified as possibly, probably and definitely related to the investigational products

  72 months

• Vaccine-specific antibody concentration (immunogenicity) measured as optical density that will be converted to concentration

  The vaccine specific antibody concentration will be assessed through specific laboratory procedures that make use of Nunc Maxisorp flat bottom plates will be coated with Ebola GP in a coating buffer. Heat inactivated serum or plasma from study participants (either diluted and or undiluted) or treated plasma sample from SUDV convalescent individuals (Positive control) or Mouse anti SUDV GP mAb (positive control) will be added to the plates and incubated. The plates will be washed and HRP goat anti-human IgG antibody and or HRP goat anti-human IgM antibody and or HRP goat anti-mouse IgG Fc or HRP goat anti-mouse IgM Fc will be added. The plates will be washed and tetramethylbenzidine (TMB) 1 component microwell peroxidase substrate added. The reaction will be stopped after about 20 minutes with hydrochloric acid. The plate's absorbance will be read at 450 nm and 630 nm. A standard curve/line will be drawn and convert the optical density to concentration

  72 months

• Vaccine specific antibody neutralization capability (immunogenicity) represented as proportion of neutralization

  Vero cells will be incubated in Eagles Minimum Essential Medium with fetal bovine serum and penicillin/streptomycin (R10) and maintained at 37°C and 5% CO2 humidified incubator. The cells will be plated onto a 96 well black flat bottomed culture plate. Study participant, positive (obtained from SUDV convalescent individuals and pre-treated) and negative controls heat inactivated serum samples will be diluted and mixed with single round infecting recombinant vesicular stomatitis virus expressing SUDV GP and firefly luciferase at room temperature with appropriate controls. The virus and serum sample mixture will be added to the plated vero cells and incubated for up to 24 hours. The virus and serum sample will be removed and vero cells lysed. Luciferase activating reagent will be added and the luminescence will be read using a luminescence plate reader. The proportion of neutralisation will be evaluated using appropriate controls (rVSV without serum).

  72 months

• Vaccine-induced T cell responses (immunogenicity) determined as spot forming units per one million cells.

  This will be done as per the standard operating procedures. IFN-γ precoated ELISPOT plates will be washed and blocked using serum. Thawed and rested PBMC will be plated, stimuli (peptides to ebola GP, appropriate positive and negative controls) added and incubated for 12 to 24 hours. The plates will be emptied and washed after incubation. Diluted enzyme-conjugate detection IFN-γ antibody will be added and incubated. The plates will be washed \& substrate added and allowed to develop for about 20 minutes. The development will be stopped by rinsing the plates in copious amounts of deionised water. The plates will be allowed to air dry in the dark and read using an ELISPOT reader within 12 hours. The results will be determined as spot forming units per one million cells

  72 months

Secondary Outcomes (1)

• Durability of the immune response measured up to 72 months quantitively by assessing the antibody concentration and qualitatively by assessing the antibody neutralization capacity. Curves will be drawn to represent immune responses against time

  72 months

Study Arms (4)

Candidate vaccine 1

EXPERIMENTAL

One injection of cAd3 will be administered to the study participants at enrollment. The participants will be monitored for 30 minutes after receipt of the vaccine and thereafter follow up done at different time points up to 72 months.

Biological: CAd3

Candidate vaccine 2

EXPERIMENTAL

One injection of chAdOx1 will be administered to the study participants at enrollment. The participants will be monitored for 30 minutes after receipt of the vaccine and thereafter follow up done at different time points up to 72 months.

Biological: ChAdox1

Candidate vaccine 3

EXPERIMENTAL

One injection of rVSV-SUDV will be administered to the study participants at enrollment. The participants will be monitored for 30 minutes after receipt of the vaccine and thereafter follow up done at different time points up to 72 months.

Biological: rVSV-SUDV

Control

PLACEBO COMPARATOR

One injection of placebo will be administered to the study participants at enrollment. The participants will be monitored for 30 minutes after receipt of the vaccine and thereafter follow up done at different time points up to 72 months.

Other: Control

Interventions

CAd3 BIOLOGICAL

CAd3 candidate vaccine which is one of the investigational products

Candidate vaccine 1

ChAdox1 BIOLOGICAL

ChAdox1 candidate vaccine which is one of the investigational products

Candidate vaccine 2

rVSV-SUDV BIOLOGICAL

rVSV-SUDV candidate vaccine which is one of the investigational products

Candidate vaccine 3

Control OTHER

Placebo

Control

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1
• Healthy volunteers aged 18-50 years from study communities
• Healthy volunteers with a permanent home address
• Able and willing to complete and provide written informed consent. In case the participant cannot read or write, the procedures must be explained to him/her and informed consent must be witnessed by a literate third party not involved with the conduct of the study
• Participant must pass the informed consent test of understanding (TOU)
• Participant must be healthy in the investigator's clinical judgement on the basis of medical history, physical examination, vital signs and point of care tests (where applicable) performed at screening
• If female of child-bearing potential and heterosexually active, practice of adequate contraception for 28 days prior to injection, negative pregnancy test on the day of vaccination, and agreement to continue adequate contraception until 90 days after vaccination
• Male participants are eligible to participate in the study if they agree to use a male condom during any heterosexual intercourse with a female of childbearing potential until 90 days after vaccination
• Phase 2
• Healthy volunteers aged 6 years-65 years from study communities. Individuals with comorbidities assessed as stable will be allowed to participate
• With a permanent home address
• Able and willing to complete and provide written informed consent or assent as applicable. In case the participant cannot read or write, the procedures must be explained to him/her, and informed consent must be witnessed by a literate third party not involved with the conduct of the study.
• Participant must pass the informed consent or assent test of understanding (TOU)
• Participant must be healthy according to the investigator's clinical judgement on the basis of medical history, physical examination, vital signs and point of care tests (where applicable) performed at screening
• If female of child-bearing potential and heterosexually active, practice of adequate contraception for 28 days prior to injection, negative pregnancy test on the day of vaccination, and agreement to continue adequate contraception until 180 days after vaccination

You may not qualify if:

• Phase 1
• History of confirmed ebola virus diseases (SUDV, EBOV or BUDV)
• Unwillingness of female participants to use effective contraception
• Participation in an interventional clinical trial within 90 days of participation in this trial
• Prior vaccination with any Ebola vaccine
• Breastfeeding or planning to conceive within 2 months following study vaccination
• Has history of fever (\>100.4ºF/38.0ºC) within 48 hours prior to enrolment into the study
• Received systemic corticosteroids exceeding physiologic replacement doses (\~5 mg/d prednisone equivalent) within 14 days prior to study entry
• Received any live virus vaccine within 30 days or any non-live virus vaccine within 14 days prior to study entry
• Has a known allergy/sensitivity or contraindication to investigational vaccines or its/their excipients?
• History of malignancy ≤5 years
• Major surgery within the 4 weeks prior to screening or planned major surgery through the course of the study (from screening until completion of the study)
• Presence of any condition that can interfere with the subject's participation for the full duration of the trial.
• HIV positive
• Hepatitis B positive

Sponsors & Collaborators

• Makerere University: lead
• Makerere University Lung Institute: collaborator
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator
• Makerere University Walter Reed Program: collaborator
• Epicentre: collaborator
• Uganda Virus Research Institute-International Aids Vaccine Initiative: collaborator
• Ministry of Health, Uganda: collaborator

Central Study Contacts

Bruce Kirenga, PhD

CONTACT

+256782404431; brucekirenga@yahoo.co.uk

Winters Muttamba, MPH

CONTACT

+256772511261; muttamba@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blinding to be done
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Model Details: A phase I/II double blind randomized clinical trial

Study Record Dates

• First Submitted: May 30, 2023
• First Posted: June 18, 2023
• Study Start: July 1, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: June 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 5 years