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Malaria,FalciparumPhase 1NCT03435874

Safety and Immunogenicity of ChAd63 RH5 and MVA RH5 in Adults, Young Children and Infants Living in Tanzania

A Phase 1 study testing ChAd63 RH5, MVA RH5 and Rabies Vaccine in people with Malaria,Falciparum, run by University of Oxford at 1 site in Tanzania.

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

This is a dose-escalation, age de-escalation randomised double-blind controlled Phase Ib trial to assess the safety, tolerability and immunogenicity of ChAd63-RH5 administered with MVA-RH5 in a heterologous prime-boost regimen. Read more about this study

Who is it for?
Ages 6 months to 35 yearsHealthy volunteers can take part
Conditions the study is for
Malaria,Falciparum
What is being tested?
ChAd63 RH5, MVA RH5 and Rabies Vaccine
Type of treatment
Vaccines
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
63 participants
Where
1 siteTanzania
Study dates
12 Apr 2018to 11 Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

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 6 months to 35 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • Only participants who meet all the inclusion criteria will be enrolled into the trial;
  • Group 1: Healthy male or female adults aged 18-35 years at the time of enrolment with signed consent.
  • Group 1 (Female only participants): Must be non-pregnant (as demonstrated by a negative urine pregnancy test), and provide consent of their willingness to take Depo-Provera contraceptive during the study and safety follow-up period.
  • Groups 2a \& 2b: Healthy male or female young children aged 1-6 years at the time of enrolment with signed consent obtained from parents or guardians.
  • Groups 3a \& 3b: Healthy male or female infants aged 6-11 months at the time of enrolment with signed consent obtained from parents or guardians.
  • Planned long-term (at least 9 months from the date of recruitment) or permanent residence in Bagamoyo town.
  • Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or young children and infants with Z-score of weight-for-age within ±2SD.

Who cannot join

  • The participant may not enter the trial if ANY of the following apply:
  • Clinically significant congenital abnormalities as judged by the PI or other delegated individual.
  • Clinically significant history of skin disorder (psoriasis, contact dermatitis etc.), allergy, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease and neurological illness as judged by the PI or other delegated individual.
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
  • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
  • Weight for age z-scores below 2 standard deviations of normal for age.
Show all 20Show fewer
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, Kathon, neomycin, betapropiolactone.
  • Any history of anaphylaxis in relation to vaccination.
  • Clinically significant laboratory abnormality as judged by the PI or other delegated individual.
  • Blood transfusion within one month of enrolment.
  • History of vaccination with previous experimental malaria vaccines.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
  • Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
  • Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG).
  • Any other finding which in the opinion of the PI or other delegated individual would increase the risk of an adverse outcome from participation in the trial.
  • Likelihood of travel away from the study area.
  • Positive malaria by blood smear at screening.
  • Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
  • Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
  • Any other significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Trial locations and contacts

1 site in 1 country.

Tanzania1 site
  • Ifakara Health Institute Clinical Trial Facility

    Bagamoyo

Other trials in Tanzania

About this study

Official title: A Phase Ib Age De-escalation Dose-escalation Randomised, Double-blind, Controlled Study of the Safety and Immunogenicity of ChAd63 RH5 and MVA RH5 Given Intramuscularly at 0 and 2-months in Healthy Adults, Children and Infants in Tanzania

This is a dose-escalation, age de-escalation randomised double-blind controlled Phase Ib trial to assess the safety, tolerability and immunogenicity of ChAd63-RH5 administered with MVA-RH5 in a heterologous prime-boost regimen. Adults (18-35 years), young children (1-6 years) and infants (6-11 months) will be enrolled in the study. Safety data will be collected for each of the vaccination regimens. The humoral and cellular immune responses generated by each of these regimens will be assessed.

Read the detailed description
  • Experimental design: Phase Ib, double blind, age de-escalation dose-escalation, randomized (2:1 ratio), controlled trial.
  • Healthy adults (18-35 years), young children (1-6 years) and infants (6-11 months) will be screened; those determined to be eligible, based on the inclusion and exclusion criteria, will be enrolled in the study.
  • Route of administration of ChAd63-RH5 (day 0) and MVA-RH5 (2 months): both vaccines will be administered by the intramuscular route to the left deltoid.
  • Each participant will be observed for at least 1 hour after vaccination to evaluate and treat any acute adverse events (AEs).
  • There will be 7-day follow-up period for solicited AEs post-vaccination: Day 0, 2 and 7 evaluations will be carried out by the study clinician at the study centre and day 1, 3, 4, 5 and 6 evaluations will be carried out by a trained community health worker in the participant's home, after each vaccination.
  • There will be a 28-day (day of vaccination and 28 subsequent days) follow-up after each vaccine dose for reporting unsolicited symptoms.
  • Serious adverse events (SAEs) will be recorded throughout the study period. Prior to vaccination, any SAEs due directly to study procedures will be captured. All SAEs will be captured beginning with the administration of the priming dose of ChAd63 RH5 and ending 4 months after the booster dose with MVA RH5.
  • Antibodies to RH5_FL will be determined at baseline and 14, 28, 56, 63, 84, 112, 140 and 168 days after ChAd63 RH5 in all participants.
  • Cellular immune responses to RH5 will be evaluated at baseline and 14 (adults only), 28, 56, 63, 84 and 168 days after ChAd63 RH5 in all participants.
  • The duration of involvement in the study from enrolment will be approximately 6 months. The vaccination phase of the study takes 9 weeks and the post-vaccination follow-up lasts for 4 months after the last dose.
Being tested
ChAd63 RH5, MVA RH5, Rabies Vaccine
Medical subject headings
Malaria, Falciparum

What participants receive

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

  • ChAd63 RH5Biological

    Vaccine

  • MVA RH5Biological

    Vaccine

  • Rabies VaccineBiological

    Vaccine

Study groups in NCT03435874
Study groupRoleWhat they receive
Group 1 ActiveExperimentaln=6. Age 18-35 years. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 at D56.
Receives: Biological: ChAd63 RH5; Biological: MVA RH5
Group 1 ComparatorPlacebo comparatorn=3. Age 18-35 years. Rabies vaccine at D0 and D56.
Receives: Biological: Rabies Vaccine
Group 2a ActiveExperimentaln=6. Age 1-6 years. 1x10 10 vp ChAd63 RH5 at D0 and 1x10 8 pfu MVA RH5 D56.
Receives: Biological: ChAd63 RH5; Biological: MVA RH5
Group 2a ComparatorPlacebo comparatorn=3. Age 1-6 years. Rabies vaccine at D0 and D56.
Receives: Biological: Rabies Vaccine
Group 2b ActiveExperimentaln=12. Age 1-6 years. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 D56.
Receives: Biological: ChAd63 RH5; Biological: MVA RH5
Group 2b ComparatorPlacebo comparatorn=6. Age 1-6 years. Rabies vaccine at D0 and D56.
Receives: Biological: Rabies Vaccine
Group 3a ActiveExperimentaln=6. Age 6-11 months. 1x10 10 vp ChAd63 RH5 at D0 and 1x10 8 pfu MVA RH5 D56.
Receives: Biological: ChAd63 RH5; Biological: MVA RH5
Group 3a ComparatorPlacebo comparatorn=3. Age 6-11 months. Rabies vaccine at D0 and D56.
Receives: Biological: Rabies Vaccine
Group 3b ActiveExperimentaln=12. Age 6-11 months. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 D56.
Receives: Biological: ChAd63 RH5; Biological: MVA RH5
Group 3b ComparatorPlacebo comparatorn=6. Age 6-11 months. Rabies vaccine at D0 and D56.
Receives: Biological: Rabies Vaccine

What is being measured

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

  1. Solicited symptoms after vaccination.

    Frequency and severity (according to internationally recognised grading tables) of local and systemic solicited adverse events will be recorded for 7 days after each vaccination. For each, a causal relationship between the adverse event and IMP will be assigned.

    Measured: 7-day surveillance after each vaccination

  2. Unsolicited symptoms after each vaccination.

    Frequency and severity (according to internationally recognised grading tables) of unsolicited adverse events will be recorded for 28 days after each vaccination. For each, a causal relationship between the adverse event and IMP will be assigned.

    Measured: 28-day surveillance after each vaccination.

  3. Serious adverse events during the study period.

    All serious adverse events from the first dose of IMP until the end of the study (approximately 6 months from first vaccination) will be recorded, causality assigned and reported to the Chief Investigator (as the Sponsor's representative) within 24 hours of the Investigator being aware of the suspected SAE. The Safety Monitoring Committee will be notified immediately by the PI if SAEs are deemed possibly, probably or definitely related to study interventions.

    Measured: Surveillance from first dose of vaccine to end of study (approximately 6 months from first vaccination).

Secondary outcomes (4)
  1. Anti-RH5 antibody concentration by ELISA.

    Evaluation of the magnitude of antibody responses to PfRH5 in adults, children and infants residing in a malaria endemic country, as measured by ELISA

    Measured: At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.

  2. Growth inhibition activity of sera from vaccinees on a panel of P. falciparum parasites.

    Evaluation of the quality of antibody responses to RH5 in adults, children and infants residing in a malaria endemic country, as measured by an assay of growth inhibition activity on the vaccinees' sera

    Measured: At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.

  3. Avidity of anti-RH5 antibodies by ELISA and surface plasmon resonance (SPR) and/or other assays (to be defined).

    Evaluation of the longevity of antibody responses to PfRH5 in adults, children and infants residing in a malaria endemic country, as measured by ELISA, SPR +/- other assays

    Measured: At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.

  4. Cellular immune responses to the RH5 by ELISpot assay and/or Intracellular Cytokine Staining (ICS) and/or other assays to be defined.

    Evaluation of the magnitude and quality of cellular immune responses to PfRH5 in adults, children and infants residing in a malaria endemic country, by ELISpot assay and/or Intracellular Cytokine Staining (ICS) and/or other assays to be defined.

    Measured: At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.

Timeline

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

  1. First posted19 Feb 2018
  2. Study start12 Apr 2018
  3. Primary completion11 Jul 2019
  4. Study completion11 Jul 2019

Resources

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
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Sequential
Model description
A Phase Ib age de-escalation dose-escalation randomised, double-blind, controlled study of the safety and immunogenicity of heterologous prime-boost with the candidate malaria vaccines ChAd63 RH5 and MVA RH5
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
63 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03435874
Sponsor's protocol ID
VAC070
Status last verified
Jan 2018
First submitted
8 Jan 2018
Last updated
4 Sep 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ChAd63 RH5, MVA RH5 and Rabies Vaccine in people with Malaria,Falciparum, run by University of Oxford at 1 site in Tanzania.

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 7 inclusion and 20 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 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Tanzania. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Solicited symptoms after vaccination. (time frame: 7-day surveillance after each vaccination). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 4 Sep 2019.

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