MSP3-CRM-Vac4All/ Alhydrogel® Vaccine

A Phase 1b/2b Double Blind, Randomized, Controlled Study of the Safety, Immunogenicity, and Efficacy of Malaria Vaccine Candidate MSP3-CRM-Vac4All/ Alhydrogel® in Young Children in Mali

Two-arm, randomized, double-blinded and controlled clinical trial to first assess the safety and tolerability of the vaccine in a Phase 1b trial and proceed to assess its efficacy against clinical malaria in young children living in highly seasonal malaria areas of Mali

Study Overview

• Status: Recruiting
• Conditions: Malaria,Falciparum
• Intervention / Treatment: Biological: MSP3-CRM-Vac4All/ Alhydrogel®; Biological: Anti-Rabies Vaccine

Detailed Description

This study is designed to be executed in two steps to achieve the primary efficacy objective:

The first step is a Phase 1b safety study, involving injections in a small safety subgroup for each dose before age-de-escalation into the younger age group and then proceeding to the second step of dosing the corresponding injection in the larger Phase 2b efficacy cohort.

Vaccination of the Phase 2b cohort will require an acceptable reactogenicity data over the first week following the corresponding vaccination of the older and younger age groups in the Phase 1 subgroup. The study DSMB will be charged with this review and ensuring that vaccination proceeds only if the reactogenicity profile meet study "go" criteria (Table 1).

The objectives of each phase are:

Phase 1b: The primary objective is to assess the safety and tolerability of the vaccine for each injection. The secondary objective is to evaluate the immune response to the vaccine and safety for up to 12 months after the first dose.

Phase 2b: The primary objective is to assess the efficacy in young children* against clinical malaria** during one transmission season. The timeline for the primary analysis assessment is from 14 days to 6 months after Dose 3.

Should the primary analysis data demonstrate that the vaccine gives good efficacy, a boost vaccination will be programmed to be administered to willing subjects before the start of the subsequent transmission season. The study protocol will be amended with the precise details in this event.

• Study Type: Interventional
• Enrollment (Anticipated): 465
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zarifah H Reed, MD, MPH; Phone Number: +33695695786; Email: zahussain22@gmail.com

Study Locations

• Mali
  • Bamako, Mali, 1805
    • Recruiting
    • Malaria Research and Training Center (MRTC), University of Sciences Techniques and Technologies of Bamako, Mali
    • Contact: Mahamadou Thera, MD; Phone Number: +223 66 74 09 61; Email: mthera@icermali.org
    • Contact: Karim Traore; Phone Number: +223 66 72 50 63; Email: Karim@icermali.org
    • Principal Investigator: Drissa Coulibaly, MD
    • Sub-Investigator: Moctar Coulibaly, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Children aged 12-59 months years old
• Healthy by medical history, physical examination and laboratory investigation
• Signed/thumb printed informed Consent by guardian/parent
• Resident in the study area villages during the whole trial period

Exclusion Criteria:

• Symptoms, physical signs of disease that could interfere with the interpretation of the trial results or compromising the health of the participants
• Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior recruitment. (For corticosteroids, this will mean prednisone, or equivalent, more or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
• Cannot be followed for any social, psychological or geographical reasons.
• Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose.
• Suspected or known hypersensitivity to any of the vaccine components or to previous vaccine.
• Clinically significant laboratory abnormalities on screened blood samples.
• Planned administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine. An exception, is the receipt of an childhood immunization program or licensed vaccine (measles, oral polio, Hib, meningococcal and combined diphtheria/pertussis/tetanus vaccines) which may be given before or after vaccination*.
• Evidence of chronic or active hepatitis B or C infection
• Presence of chronic illness that, in the judgment of the investigator, would interfere with the study outcomes or pose a threat to the participant's health.
• Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period
• History of surgical splenectomy.

• Moderate or severe malnutrition at screening based on clinical judgement.

  o (Weight-for-age Z score of less than -3 or other clinical signs of malnutrition).

• Previous participation to a malaria vaccine trial
• Known history of HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Vaccine; MSP3-CRM-Vac4All/ Alhydrogel®	Biological: MSP3-CRM-Vac4All/ Alhydrogel®; 30 microgram MSP3-CRM-Vac4All protein extemporaneously formulated with Alhydrogel® adjuvant
Active Comparator: Control Vaccine; Anti-rabies vaccine	Biological: Anti-Rabies Vaccine; Control vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protective Efficacy against Clinical Malaria	To assess the efficacy of 30 µg MSP3-CRM-Vac4All/Alhydrogel® vaccine in children ages 12-60 months old, against clinical malaria occurring over one transmission season. The primary efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL	The timeline for assessment will be from 14 days to 6 months after Dose 3.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy- different definitions of malaria fever and parasite thresholds on microscopy	To compare efficacy against clinical malaria for different case definitions using; Fever thresholds that are higher than 37.5ºC, such as 38.5ºC and 39.5ºC; History of fever instead of measured fever; Different parasitemia by microscopy thresholds [any parasitemia, 1000, 10,000 and 20,000/µL] Efficacy outcomes; clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 38.5ºC with P. falciparum parasitemia ≥5000/µL or ≥ 39.5ºC with P. falciparum parasitemia ≥5000/µL or; clinical malaria episodes defined as history of fever with P. falciparum parasitemia of the following levels: any parasitemia, 1000, 10,000 and 20,000/µL clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 38.5ºC with or ≥ 39.5ºC with P. falciparum parasitemia of the following levels: any parasitemia, 1000, 10,000 and 20,000/µL	For 12 months after first vaccination
Efficacy duration	To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring during the 12 months following dose 3.	For 12 months following the first vaccination
Efficacy against first malaria episodes	To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against first clinical malaria episodes occurring from over the 6 month period 14 days after 2nd and 3rd vaccination and up to the end of study follow-up (12 months after first vaccination). The efficacy outcome is first episode of clinical malaria, with the case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL	From 14 days post 2nd or 3rd vaccination to 6 months following and up to the end of study follow-up (12 months after first vaccination
Efficacy (conditional boost)	To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring The efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL	For the 6 months following boost vaccination
Efficacy (conditional boost)	To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring. The efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL	For the 12 months following boost vaccination
Number of adverse events	To assess the safety and reactogenicity of 3 doses of 30 µg MSP3-CRM-Vac4All/Alhydrogel® given at D0, D28 and D56 in healthy young children	During the month following each vaccination, and 6 months and 12 months after first vaccination.
Number of adverse events for conditional boost vaccination	Safety and reactogenicity of boost vaccination doses of MSP3-CRM-Vac4All/Alhydrogel® in healthy young children	At one month, 6 month and 12 months following boost vaccination
Immune response	To examine the duration of immune responses of a 3-dose regimen of during periods corresponding to that used for primary and other secondary efficacy endpoints as measured through a > 5-fold decrease of MSP3-specific serum IgG antibody titers after each vaccination in comparison to baseline levels (14 days post last dose)	From 14 days post last dose to up to a month after last dose, 6 months after last dose and 12 months after first dose
Immune response	To determine immunogenicity in terms of the proportion with titres either more than 3SD above the median for negative controls (positive) or at least 50% of the positive controls (strongly positive) after dose 3.	A month after dose 3
Parasite densities	To measure effect on parasitemia by comparing parasite densities in malaria episodes occurring in vaccinees compared to control	From vaccination to up to 6 months after last dose and 12 months after first dose.

Collaborators and Investigators

• Sponsor: Vac4All
• Collaborators: Malaria Research and Training Center, Bamako, Mali
• Investigators: Study Director: Manamadou Thera, MD, MRTC, University of Sciences Techniques and Technologies of Bamako, Mali Locations:

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2023
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): August 31, 2024

Study Registration Dates

• First Submitted: February 25, 2023
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: malaria; malaria vaccine; vaccine efficacy
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Antacids; Aluminum Hydroxide
• Other Study ID Numbers: V4ALL/MSP3/009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No