MalariaPhase 1NCT00349713
FMP2.1/AS02A: Rabies Vaccine Malaria-Experienced Adults in Bandiagara, Mali
A Phase 1 study testing FMP2.1/AS02A and Rabies vaccine (RabAvert) in people with Malaria and Plasmodium Falciparum Malaria, run by U.S. Army Medical Research and Development Command at 1 site in Mali.
Trial summary
Malaria is a disease that affects many people in Africa and in Mali. It is caused by germs that are spread by mosquito bites. This study will look at the safety, effectiveness, and best dose of an experimental malaria vaccine in people who are regularly exposed to malaria. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Plasmodium Falciparum Malaria
- What is being tested?
- FMP2.1/AS02A and Rabies vaccine (RabAvert)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteMali
- Study dates
- Nov 2004to Dec 2006
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- A male or non-pregnant female aged 18-55 years inclusive at the time of screening
- For women, willingness not to become pregnant until 1 month after the last immunization (pre-menopausal female participants will be referred to the local family planning clinic in Bandiagara, which offers several means of contraception that are approved and recommended by the Malian Ministry of Health)
- Separate written informed consent obtained from the participant before screening and study start, respectively
- Available and willing to participate in follow-up for the duration of study (12 months)
Who cannot join
- Previous vaccination with any investigational vaccine or with any rabies vaccine
- Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first study immunization, or planned use up to 30 days after the third immunization
- Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first immunization. This will include any dose level of oral steroids or inhaled steroids, but not topical steroids
- Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first study immunization with the exception of tetanus toxoid
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
- Any confirmed or suspected autoimmune disease
Show all 24Show fewer
- History of allergic reactions or anaphylaxis to immunizations or to any vaccine component
- History of serious allergic reactions to any substance, requiring hospitalization or emergent medical care
- History of allergy to tetracycline, doxycycline, nickel, Imidazole, chicken eggs, processed bovine gelatin, chicken protein, neomycin, or amphotericin B
- History of splenectomy
- Serum ALT >/=43 IU/L
- Serum creatinine level >113 µmol /L for males and 70 µmol /L for females
- Hgb <11 g/dL for males and <10 g/dL for females
- WBC <4.0 x 1000/cubic mm or >13 x 1000/cubic mm
- Absolute lymphocyte count </=1.4 x 1000 /µl
- Thrombocytopenia < 108,000/µl
- More than trace protein, more than trace hemoglobin or positive glucose in urine
- Administration of immunoglobulins and/or any blood products within the three months preceding the first study immunization or planned administration during the study period
- Suspected or known current alcohol or illicit drug abuse
- Pregnancy or positive urine beta-HCG on the day of or prior to immunization
- Breastfeeding
- Simultaneous participation in any other interventional clinical trial
- Acute or chronic pulmonary, cardiovascular, hepatic, renal or neurological condition, or any other findings that in the opinion of the Principal Investigator (PI) may increase the risk of participating in the study
- Other condition that in the opinion of the PI would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double Blind Randomized, Controlled Phase 1 Dose Escalation Trial to Evaluate the Safety and Immunogenicity of the WRAIR AMA1 Malaria Antigen (FMP2.1) Adjuvanted in GSK's AS02A Versus Rabies Vaccine in Malaria-experienced Adults in Bandiagara, Mali
Malaria is a disease that affects many people in Africa and in Mali. It is caused by germs that are spread by mosquito bites. This study will look at the safety, effectiveness, and best dose of an experimental malaria vaccine in people who are regularly exposed to malaria. Study participants will be 60 adults, 18-55 years old, who live in Bandiagara, Mali. Volunteers will get either 3 full doses of the experimental malaria vaccine, 3 half doses of the malaria vaccine, or a rabies vaccine that has been approved in Mali. (Rabies is an infection of the brain that usually causes death, and can be caught from being bitten by infected dogs or bats.) The 3 vaccinations will be given by injection into the upper arm 30 days apart. Volunteers will be enrolled in the study for approximately 12 months after the first vaccination. Volunteers will have 14 blood samples collected during the study for testing to make sure that the vaccine is not harmful and to measure the effect of the vaccine.
Read the detailed description
The primary objective of this study is to evaluate the safety and reactogenicity of two dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Secondary objectives are to: (1) measure the magnitude and duration of antibody response to FMP2.1; (2) measure cellular immune responses to FMP2.1 at baseline and after immunization; (3) measure the inhibition of parasite growth by the in vitro GIA; and (4) determine the specificity of the antibodies to diverse AMA1 genotypes in addition to 3D7, by measuring by ELISA, and GIA on parasites with typed AMA1. A double-blind controlled dose escalation trial will allow assessment of vaccine safety in each of three groups, one group each to receive medium and full dose levels of the experimental vaccine, and one group to receive the comparator vaccine. Thirty adults will be randomized to receive the medium dose level of FMP2.1 (n=20) or rabies vaccine (n=10) and thirty to receive the full dose level of FMP2.1 (n=20) or rabies vaccine (n=10). The division of the rabies group into two groups of ten is done to maintain blinding at each immunization time point, and all participants who receive the rabies vaccine will be analyzed as a single group. The sample size of the groups, however, will not allow detection of anything other than very large differences in the occurrence of adverse events among the three groups. The advantage of double blinding is to remove the potential for investigator and participant prejudgment about the effects of the vaccines in the reporting of adverse events.
- Conditions
- Malaria, Plasmodium Falciparum Malaria
- Being tested
- FMP2.1/AS02A, Rabies vaccine (RabAvert)
- Keywords
- Plasmodium falciparum Malaria, Mali, adjuvant
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FMP2.1/AS02ABiological
FMP2.1 in GSK Biologicals' AS02A
Rabies vaccine (RabAvert)Biological
RabAvert Rabies vaccine
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: 25ug FMP2.1 / AS02A | Experimental | 20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A Receives: Biological: FMP2.1/AS02A |
| Cohort 2: 50ug FMP2.1 / AS02A | Experimental | 20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A Receives: Biological: FMP2.1/AS02A |
| Cohorts 1 and 2: Rabies vaccine (RabAvert) | Active comparator | 20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2
Rabies vaccine (RabAvert): RabAvert Rabies vaccine Receives: Biological: FMP2.1/AS02A; Biological: Rabies vaccine (RabAvert) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Reactogenicity (SAEs and AEs)
The primary objective was to evaluate the safety and reactogenicity of 2 dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' (GSK) AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Solicated AEs were recorded for the 7 day surveillance period after each vaccination. Unsolicited AEs were recorded for 30 days after each vaccination.
Measured: 12 months
Secondary outcomes (4)
Antibody Response to FMP2.1 Over Time
Measurement of anti-AMA1 antibody titers over time
Measured: 90 Days
Anti-AMA1 Log Antibody Titers Over Time
Summary of Anti-AMA1 Log Antibody titers on days 0, 14, 30, 44, 60, 74 and 90
Measured: 90 Days
Geometric Mean Antibody Titers Over Time
Measurement of geometric mean antibody titers on days 0, 14, 30, 44, 60, 74 and 90
Measured: 90 Days
Subjects With 2- and 4-fold Increases in Anti-FMP2.1 Antibody Levels Over Time
Proportion of Subjects with 2- and 4-fold increases in Anti-FMP2.1 Antibody levels on days 14, 30, 44, 60, 74 and 90
Measured: 90 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2006 (estimated)
- Study startNov 2004
- Primary completionDec 2005
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Walter Reed Army Institute of Research (WRAIR), GlaxoSmithKline, University of Maryland
- Responsible party
- Sponsor
- Investigators
- Mahamadou A. Thera, M.D., Principal investigator, University of BamakoChris V. Plowe, M.D., Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00349713
- Sponsor's protocol ID
- 04-031
- Other IDs
- N01AI085346-006, N01AI085346-005, N01AI085346-000, 102231 ( Malaria-037), HSRRB A-12855
- Status last verified
- Apr 2017
- First submitted
- 6 Jul 2006
- Last updated
- 24 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Plan to share data with National Institute of Allergy and Infectious Diseases (NIAID) Walter Reed Army Institute of Research (WRAIR) GlaxoSmithKline University of Maryland
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Randomized, Controlled Phase 1 Dose Escalation Trial to Evaluate the Safety and Immunogenicity of the WRAIR AMA1 Malaria Antigen (FMP2.1) Adjuvanted in GSK's AS02A Versus Rabies Vaccine in Malaria-experienced Adults in Bandiagara, Mali
- ClinicalTrials.gov ID
- NCT00349713
- Acronym / sponsor ID
- 04-031
- Conditions
- Malaria, Plasmodium Falciparum Malaria
- Keywords
- Plasmodium falciparum Malaria, Mali, adjuvant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Walter Reed Army Institute of Research (WRAIR), GlaxoSmithKline, University of Maryland
- Study start
- Nov 2004
- Primary completion
- Dec 2005 (actual)
- Study completion
- Dec 2006 (actual)
- First posted
- 10 Jul 2006 (estimated)
- Results
- Posted 24 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Malaria is a disease that affects many people in Africa and in Mali. It is caused by germs that are spread by mosquito bites. This study will look at the safety, effectiveness, and best dose of an experimental malaria vaccine in people who are regularly exposed to malaria. Study participants will be 60 adults, 18-55 years old, who live in Bandiagara, Mali. Volunteers will get either 3 full doses of the experimental malaria vaccine, 3 half doses of the malaria vaccine, or a rabies vaccine that has been approved in Mali. (Rabies is an infection of the brain that usually causes death, and can be caught from being bitten by infected dogs or bats.) The 3 vaccinations will be given by injection into the upper arm 30 days apart. Volunteers will be enrolled in the study for approximately 12 months after the first vaccination. Volunteers will have 14 blood samples collected during the study for testing to make sure that the vaccine is not harmful and to measure the effect of the vaccine.
Detailed description
The primary objective of this study is to evaluate the safety and reactogenicity of two dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Secondary objectives are to: (1) measure the magnitude and duration of antibody response to FMP2.1; (2) measure cellular immune responses to FMP2.1 at baseline and after immunization; (3) measure the inhibition of parasite growth by the in vitro GIA; and (4) determine the specificity of the antibodies to diverse AMA1 genotypes in addition to 3D7, by measuring by ELISA, and GIA on parasites with typed AMA1. A double-blind controlled dose escalation trial will allow assessment of vaccine safety in each of three groups, one group each to receive medium and full dose levels of the experimental vaccine, and one group to receive the comparator vaccine. Thirty adults will be randomized to receive the medium dose level of FMP2.1 (n=20) or rabies vaccine (n=10) and thirty to receive the full dose level of FMP2.1 (n=20) or rabies vaccine (n=10). The division of the rabies group into two groups of ten is done to maintain blinding at each immunization time point, and all participants who receive the rabies vaccine will be analyzed as a single group. The sample size of the groups, however, will not allow detection of anything other than very large differences in the occurrence of adverse events among the three groups. The advantage of double blinding is to remove the potential for investigator and participant prejudgment about the effects of the vaccines in the reporting of adverse events.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: 25ug FMP2.1 / AS02A | Experimental | Biological: FMP2.1/AS02A20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A |
| Cohort 2: 50ug FMP2.1 / AS02A | Experimental | Biological: FMP2.1/AS02A20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A |
| Cohorts 1 and 2: Rabies vaccine (RabAvert) | Active comparator | Biological: FMP2.1/AS02A, Biological: Rabies vaccine (RabAvert)20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- A male or non-pregnant female aged 18-55 years inclusive at the time of screening
- For women, willingness not to become pregnant until 1 month after the last immunization (pre-menopausal female participants will be referred to the local family planning clinic in Bandiagara, which offers several means of contraception that are approved and recommended by the Malian Ministry of Health)
- Separate written informed consent obtained from the participant before screening and study start, respectively
- Available and willing to participate in follow-up for the duration of study (12 months)
Key exclusion criteria (24 listed)
- Previous vaccination with any investigational vaccine or with any rabies vaccine
- Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first study immunization, or planned use up to 30 days after the third immunization
- Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first immunization. This will include any dose level of oral steroids or inhaled steroids, but not topical steroids
- Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first study immunization with the exception of tetanus toxoid
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FMP2.1/AS02AFMP2.1 in GSK Biologicals' AS02A | Biological | Cohort 1: 25ug FMP2.1 / AS02A, Cohort 2: 50ug FMP2.1 / AS02A, Cohorts 1 and 2: Rabies vaccine (RabAvert) |
| Rabies vaccine (RabAvert)RabAvert Rabies vaccine | Biological | Cohorts 1 and 2: Rabies vaccine (RabAvert) |
Primary outcome
Safety and Reactogenicity (SAEs and AEs)
Time frame: 12 months
The primary objective was to evaluate the safety and reactogenicity of 2 dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' (GSK) AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Solicated AEs were recorded for the 7 day surveillance period after each vaccination. Unsolicited AEs were recorded for 30 days after each vaccination.
4 secondary outcomes
Antibody Response to FMP2.1 Over Time
Time frame: 90 Days
Anti-AMA1 Log Antibody Titers Over Time
Time frame: 90 Days
Geometric Mean Antibody Titers Over Time
Time frame: 90 Days
Subjects With 2- and 4-fold Increases in Anti-FMP2.1 Antibody Levels Over Time
Time frame: 90 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Plan to share data with National Institute of Allergy and Infectious Diseases (NIAID) Walter Reed Army Institute of Research (WRAIR) GlaxoSmithKline University of Maryland
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mahamadou A. Thera, M.D. principal investigator
University of Bamako
Chris V. Plowe, M.D. principal investigator
University of Maryland, Baltimore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FMP2.1/AS02A and Rabies vaccine (RabAvert) in people with Malaria and Plasmodium Falciparum Malaria, run by U.S. Army Medical Research and Development Command at 1 site in Mali.
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 4 inclusion and 24 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 24 Jul 2017. 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 Mali. 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. 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?
Yes. Results are posted in the registry (first posted 24 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety and Reactogenicity (SAEs and AEs) (time frame: 12 months). 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 24 Jul 2017.