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

NCT03435874 | Completed Phase 1 DMC

• 1 other identifier: VAC070
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (3)

• 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.

  7-day surveillance after each vaccination

• 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.

  28-day surveillance after each vaccination.

• 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.

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

Secondary Outcomes (4)

• Anti-RH5 antibody concentration by ELISA.

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

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

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

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

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

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

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

Study Arms (10)

Group 1 Active

EXPERIMENTAL

n=6. Age 18-35 years. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 at D56.

Biological: ChAd63 RH5; Biological: MVA RH5

Group 1 Comparator

PLACEBO COMPARATOR

n=3. Age 18-35 years. Rabies vaccine at D0 and D56.

Biological: Rabies Vaccine

Group 2a Active

EXPERIMENTAL

n=6. Age 1-6 years. 1x10 10 vp ChAd63 RH5 at D0 and 1x10 8 pfu MVA RH5 D56.

Biological: ChAd63 RH5; Biological: MVA RH5

Group 2a Comparator

PLACEBO COMPARATOR

n=3. Age 1-6 years. Rabies vaccine at D0 and D56.

Biological: Rabies Vaccine

Group 2b Active

EXPERIMENTAL

n=12. Age 1-6 years. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 D56.

Biological: ChAd63 RH5; Biological: MVA RH5

Group 2b Comparator

PLACEBO COMPARATOR

n=6. Age 1-6 years. Rabies vaccine at D0 and D56.

Biological: Rabies Vaccine

Group 3a Active

EXPERIMENTAL

n=6. Age 6-11 months. 1x10 10 vp ChAd63 RH5 at D0 and 1x10 8 pfu MVA RH5 D56.

Biological: ChAd63 RH5; Biological: MVA RH5

Group 3a Comparator

PLACEBO COMPARATOR

n=3. Age 6-11 months. Rabies vaccine at D0 and D56.

Biological: Rabies Vaccine

Group 3b Active

EXPERIMENTAL

n=12. Age 6-11 months. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 D56.

Biological: ChAd63 RH5; Biological: MVA RH5

Group 3b Comparator

PLACEBO COMPARATOR

n=6. Age 6-11 months. Rabies vaccine at D0 and D56.

Biological: Rabies Vaccine

Interventions

ChAd63 RH5 BIOLOGICAL

Vaccine

Group 1 Active; Group 2a Active; Group 2b Active; Group 3a Active; Group 3b Active

MVA RH5 BIOLOGICAL

Vaccine

Group 1 Active; Group 2a Active; Group 2b Active; Group 3a Active; Group 3b Active

Rabies Vaccine BIOLOGICAL

Vaccine

Group 1 Comparator; Group 2a Comparator; Group 2b Comparator; Group 3a Comparator; Group 3b Comparator

Eligibility Criteria

• Age: 6 Months - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Oxford: lead
• Ifakara Health Institute: collaborator
• Medical Research Council: collaborator

Study Sites (1)

Ifakara Health Institute Clinical Trial Facility

Bagamoyo, Tanzania

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Angela M Minassian

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: February 19, 2018
• Study Start: April 12, 2018
• Primary Completion: July 11, 2019
• Study Completion: July 11, 2019
• Last Updated: September 4, 2019

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

TA (1)