- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01341704
Proof-of-Concept Study of MSP3-LSP Vaccine to Protect Against Malaria in Africa (MSP3-POC)
Phase 2B Double Blind, Randomized, Controlled Trial to Evaluate the Safety, Immunogenicity and Protective Efficacy of MSP3-LSP Vaccine Candidate Adjuvanted in Aluminium Hydroxide (AIOH) Against Plasmodium Falciparum Clinical Malaria in Healthy Children Aged 12-48 Months in Mali
Hypothesis: The MSP3-LSP/Alum vaccine, administered to children will have a protective efficacy of at least 30% (lower bound of confidence interval of 0) against malaria disease occurring during a period beginning from 14 days after the 3rd immunization until 1 year after.
The primary objective of this double-blind, randomized, controlled trial will be to assess the clinical efficacy of MSP3-LSP/AlOH vaccine when administered by subcutaneous route in children aged 12-48 months against all clinical malaria episodes occurring during a period beginning from 14 days after the 3rd immunization until 3 months after 3rd immunization, when administered according to the following schedule:- Primary administration: Three doses of administered 4 weeks apart
Secondary administration (Boost): One dose 3 months after the third dose in year 1 of the trial; and two doses, given exactly one year after the date corresponding to the third dose and the first boost given during Year 1
Case definition for an episode of malaria is a febrile illness with axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥ 5000 per μL
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a Phase 2 b, randomized, controlled trial, comparing MSP3-LSP experimental malaria vaccine with the comparator Verorab rabies vaccine (primary series) and normal saline (secondary/booster series). The trial is being conducted in two sites, Doneguebougou and surroundings (Koulikoro) and Bougoula Hameau and surroundings (Sikasso).
Each site will enroll 400 subjects. Subjects aged 12-48 months will be enrolled and randomized in a 1:1 ratio to receive either 30 µg of MSP3-LSP/AlOH in 0.5 mL or the control vaccine, Verorab Rabies subcutaneously.
The primary series of vaccinations will be given on days 0, 28 and 56. The first of the secondary/booster series will be administered 3 months after completing the primary series (D146) in Year 1, and the subsequent booster doses will be administered one year after the 3rd dose (D416) and one year after the first booster dose (D506) in Year 2.
For safety, occurrence of adverse events will be solicited during daily home visit by field workers for 6 days after each vaccination. Unsolicited adverse events will be documented for the following 28 days after each dose.
For efficacy, suspect cases will be detected through weekly home visits following the 1st vaccination and continuing throughout the duration of the trial.
In addition to active case detection through home visits, parents and care-givers of the subjects will be advised of signs and symptom of illness and instructed to bring sick children to the on-site clinic for assessment and treatment. Study clinical staff will be available round-the clock for the entire duration of the trial. During these unscheduled visits malaria smears, blood paper filter and hemoglobin will be done in case of signs or symptoms compatible with clinical malaria.
Children will be followed for two years following the first vaccination. Clinic visits are scheduled throughout the follow-up period for clinical assessment, malaria smear, blood paper filter and hemoglobin systematically on days 0, 28, 56, 86, 116, 146, 180, 236, 326, 416, 446, 506, 536 and 730. The humoral immune response to the vaccine antigen will be assessed using ELISA on days 0, 28, 56, 86, 116, 146, 180, 236, 416, 446, 506, and 730. Cellular immune responses to the vaccine antigens (MSP3-LSP and peptides a,b,c,d) will be assessed on days 0, 86,146, and 416 using CBA on a subset of 50 MSP3 vaccinated individuals. The functionality of the induced immune responses using Western Blot (WB) method and ADCI technique will be evaluated at screening and on days 86, 146, 236, 416, 506 and 730.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Bamako, Mali, 1805
- Malaria Research and Training Center Department of Epidemiology of Parasitic Diseases Faculty of Medicine, Pharmacy and Dentistry University of Bamako BP 1805, Point G Bamako, Mali, West Africa Tel/Fax 223-2022-8109
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Children aged 12-48 months 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 subjects
- Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior recruitment. (for corticosteroids, this will mean prednisone, or equivalent, ≥ 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.
- 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 EPI or licensed vaccine (measles, oral polio, Hib, meningococcal and combined diphtheria/pertussis/tetanus vaccines) which may be given 14 days or more 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 defined as weight for age Z-score less than 2
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MSP3-LSP/AlOH
Synthetic polyprotein of 96 amino acids (186-276 in 3D7 strain) manufactured by solid-phase synthesis by SYNPROSIS, France; lyophilized product was formulated extemporaneously with aluminum hydroxide (Reheis).
30 microgram per dose; three dose schedule on study day 0, 28 and 56 for primary series
|
30 µg of test vaccine MSP3-LSP/AlOH, administered by subcutaneous route according to the following schedule:- Primary administration: Three doses administered at 4 weeks interval: D0, D28 (± 2 days), D56 (± 4 days) Secondary administration (Boost): Year 1: One dose 3 months after the third dose Year 2: Two doses, given exactly one year after the date corresponding to the third dose and the first boost given during Year 1 |
Placebo Comparator: Control
Primary series: Verorab Rabies vaccine; Secondary/Booster series: 0.9% NaCL/Normal Saline
|
The Verorab rabies vaccine will be given as control for the primary series of the experimental vaccine.
It consists of inactivated rabies virus produced in vero cells (Wistar Rabies PM/W138 1503-3M (inactivated).
Manufacturer SANOFI PASTEUR SA.
Presentation is 0.5 ml per dose in a pre-filled syringe.
0.5 ml per dose; to be given as control for the secondary/booster doses of experimental vaccine
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of episodes of clinical malaria occurring during a period beginning from 14 days after the 3rd immunization until 3 months after 3rd immunization in all subjects.
Time Frame: 3 months
|
A clinical malaria episode is defined as a febrile illness with a documented axillary temperature of
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of subjects with solicited adverse events
Time Frame: 7 days following each vaccination
|
In this study, the following symptoms will directly be solicited for during 7 days immediately following each vaccination. Solicited Local (injection site) adverse events
Solicited systemic adverse events
|
7 days following each vaccination
|
Number of subjects with unsolicited adverse events
Time Frame: 30 days following each vaccination
|
All the adverse events/reactions, whether observed by the investigator or reported by the subject, will be documented.
For each event/reaction the following details will be recorded: 1) description of the event(s)/reaction(s), 2) date and time of occurrence, 3) duration, 4) intensity, 5)assessment of relationship to the vaccine, 6) action taken including treatment, 7) outcome.
|
30 days following each vaccination
|
Number of subjects with serious adverse events
Time Frame: 2 years
|
A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose:
|
2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mahamadou Sissoko, MD, Malaria Research and Training Center Department of Epidemiology of Parasitic Diseases Faculty of Medicine, Pharmacy and Dentistry University of Bamako BP 1805, Point G Bamako, Mali, West Africa
- Study Director: Pierre L Druilhe, MD, CEO, Vac4All
- Study Director: Ogobara Doumbo, MD, Chief, MRTC
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MMVDU-013
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
Clinical Trials on MSP3-LSP/AlOH
-
African Malaria Network TrustUnknown
-
Lupin Research IncCompleted
-
Magnolia Medical Technologies, Inc.CompletedSepticemiaUnited States
-
Cellphire Therapeutics, Inc.Department of Health and Human ServicesTerminatedMyelodysplastic Syndromes | Myeloproliferative Disorders | Thrombocytopenia | Hematologic Malignancy | Bone Marrow Aplasia | Platelet RefractorinessUnited States, Israel, Norway
-
Zagazig UniversityRecruiting
-
European Malaria Vaccine InitiativeUnknown
-
Magnolia Medical Technologies, Inc.Terminated
-
African Malaria Network TrustLondon School of Hygiene and Tropical MedicineUnknown
-
U.S. Army Medical Research and Development CommandCompleted
-
Lupin Research IncCompleted