MalariaPhase 1NCT00308061
Safety Study of Candidate Malaria Vaccine FMP1/AS02A in Healthy Adults in Bandiagara, Mali
A Phase 1 study testing FMP1/AS02A and Imovax Rabies Vaccine in people with Malaria, run by U.S. Army Medical Research and Development Command at 1 site in Mali.
Trial summary
This study tested the safety of a new malaria vaccine in adults in Mali, West Africa, and measured the ability of the vaccine to stimulate antibodies directed against the malaria protein that the vaccine is based on. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- FMP1/AS02A and Imovax Rabies Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteMali
- Study dates
- Jul 2003to Jul 2005
- 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 dose of vaccine
- Written informed screening and study consent obtained from the participant before study start.
- Available and willing to participate in follow-up for the duration of study (12 months)
Who cannot join
- Previous vaccination with an investigational malaria 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 dose of study vaccine, or planned use up to 30 days after the third dose.
- Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first vaccine dose. This will include oral steroids and inhaled steroids, but not topical steroids.
- Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of study vaccine(s) with the exception of tetanus toxoid.
- Previous vaccination with a vaccine containing MPL and/or QS-21 such as RTS,S.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
Show all 25Show fewer
- Any confirmed or suspected autoimmune disease
- 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 or neomycin
- History of splenectomy
- Serum ALT >=35 IU/L
- Serum creatinine level >133 micro moles per Liter (1.5 mg/dL)
- Hb <11 g/dL for males and <10 g/dL for females
- WBC <3.0 x 103/mm3 or >13.5 x 103/mm3
- Absolute lymphocyte count <=1.0 x 103 per micro liter
- Thrombocytopenia < 100,000 per micro liter
- 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 dose of study vaccine 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 neurologic condition, or any other findings that in the opinion of the PI may increase the risk to the participant from participating in the study.
- Other condition that in the opinion of the investigator 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 I Trial to Evaluate the Safety and Immunogenicity of WRAIR's MSP1 Candidate Malaria Vaccine (FMP1) Adjuvant in GSK Bio's AS02A vs. Rabies Vaccine in Semi-immune Adults in Bandiagara, Mali.
This study tested the safety of a new malaria vaccine in adults in Mali, West Africa, and measured the ability of the vaccine to stimulate antibodies directed against the malaria protein that the vaccine is based on. Forty adults were randomly assigned to get either the experimental malaria vaccine or a rabies vaccine, for comparison.
Read the detailed description
The study was a randomized, controlled trial in which participants and clinical investigators were blinded to vaccine group assignment. Forty adults were randomized in a 1:1 ratio to receive either FMP1/AS02A or the control rabies vaccine. The aims of the control group were to account for baseline morbidity and the impact of seasonal malaria transmission on the dynamics of anti-MSP-1 antibodies, and to minimize bias in assessment of adverse events. Vaccines were given on a 0-, 1- and 2-month schedule. The first immunization was given in early July just as malaria transmission began; the second dose at the end of July as transmission was increasing; and the third dose in late August near the peak of malaria transmission intensity. Study day 90 was in October, shortly after transmission crests and when severe and uncomplicated malaria disease episodes peak, study day 180 was at the end of the malaria season, and study day 272 was at the height of the dry season. The final study follow-up on day 364 coincided with the beginning of the 2004 malaria season. Interim safety analyses were reviewed by an independent Safety Monitoring Committee before the second and third immunizations.
- Conditions
- Malaria
- Being tested
- FMP1/AS02A, Imovax Rabies Vaccine
- Keywords
- Plasmodium falciparum, malaria, merozoite surface protein-1
- 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.
FMP1/AS02ABiological
FMP1 antigen contained 62.5 ug of lyophilized protein with 3.1 percent lactose as cryoprotectant. It's reconstituted in approx. 600 uL AS02A adjuvant manufactured by GSK. AS02A contains 50 ug MPL and 50ug QS21, 250uL of SB62 (oil/water emulsion) in phosphate buffered saline (PBS) per volume of 0.5 mL. All AS02A vials contained 0.65 to 0.75 mL of liquid.
Imovax Rabies VaccineBiological
Sterile, stable, freeze-dried suspension of rabies virus prepared from the strain PM-1503-3M, obtained from the Wistar Inst. in Philadelphia. Each 1 mL dose of vaccine contained 100 mg of human albumin, <150g of neomycin sulfate, and >2.5 IU of rabies antigen.
| Study group | Role | What they receive |
|---|---|---|
| FMP1/AS02A Vaccine | Experimental | 500 uL of FMP1/AS02A is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle Receives: Biological: FMP1/AS02A |
| Imovax Rabies Vaccine | Active comparator | 1 mL of Imovax Rabies Vaccine is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle Receives: Biological: Imovax Rabies Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Solicited Adverse Events by Immunization and Type
Number of participants with solicited adverse events by immunization and type (local, general and any) during each of the three eight-day follow-up periods after each vaccination (day of vaccination and post-vaccination days 1, 2, 3, and 7). Subjects were immunized on days 0, 30+7, and 60+7.
Measured: Days 0, 1, 2, 3, 7, 30, 31, 32, 33, 37, 60, 61, 62, 63, 67
Secondary outcomes (1)
Geometric Mean Titers for Anti-FMP1 Antibody
Immune response was measured by anti-FMP1 endpoint titers. Data were obtained on day 0, 14, 30, 44, 60, 74, 90, 180, 272, and 364. Samples collected on vaccination days (days 0, 30, and 60) were collected immediately prior to vaccination.
Measured: Days 0, 14, 30, 44, 60, 74, 90, 180, 272, and 364
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2006 (estimated)
- Study startJul 2003
- Primary completionSep 2004
- Study completionJul 2005
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.
- Publications (3)Papers the sponsor has linked to this study.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 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, United States Agency for International Development (USAID)
- Investigators
- Mahamadou A Thera, MD MPH, Principal investigator, University of Bamako Faculty of Medicine, Mali
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00308061
- Sponsor's protocol ID
- WRAIR 1029
- Other IDs
- NIH DMID 02-184, Univ of Maryland IRB 0303311, HSRRB A-12093, NIAID IRB 177
- Status last verified
- May 2017
- First submitted
- 24 Mar 2006
- Last updated
- 31 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Publications
Stoute JA, Gombe J, Withers MR, Siangla J, McKinney D, Onyango M, Cummings JF, Milman J, Tucker K, Soisson L, Stewart VA, Lyon JA, Angov E, Leach A, Cohen J, Kester KE, Ockenhouse CF, Holland CA, Diggs CL, Wittes J, Heppner DG Jr; MSP-1 Malaria Vaccine Working Group. Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya. Vaccine. 2007 Jan 2;25(1):176-84. doi: 10.1016/j.vaccine.2005.11.037. Epub 2005 Dec 7.
PubMed 16388879Ockenhouse CF, Angov E, Kester KE, Diggs C, Soisson L, Cummings JF, Stewart AV, Palmer DR, Mahajan B, Krzych U, Tornieporth N, Delchambre M, Vanhandenhove M, Ofori-Anyinam O, Cohen J, Lyon JA, Heppner DG; MSP-1 Working Group. Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine. 2006 Apr 5;24(15):3009-17. doi: 10.1016/j.vaccine.2005.11.028. Epub 2005 Nov 28.
PubMed 16356603Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Kone AK, Guindo AB, Traore K, Dicko A, Sagara I, Sissoko MS, Baby M, Sissoko M, Diarra I, Niangaly A, Dolo A, Daou M, Diawara SI, Heppner DG, Stewart VA, Angov E, Bergmann-Leitner ES, Lanar DE, Dutta S, Soisson L, Diggs CL, Leach A, Owusu A, Dubois MC, Cohen J, Nixon JN, Gregson A, Takala SL, Lyke KE, Plowe CV. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial. PLoS One. 2008 Jan 23;3(1):e1465. doi: 10.1371/journal.pone.0001465.
PubMed 18213374
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Randomized Controlled Phase I Trial to Evaluate the Safety and Immunogenicity of WRAIR's MSP1 Candidate Malaria Vaccine (FMP1) Adjuvant in GSK Bio's AS02A vs. Rabies Vaccine in Semi-immune Adults in Bandiagara, Mali.
- ClinicalTrials.gov ID
- NCT00308061
- Acronym / sponsor ID
- WRAIR 1029
- Conditions
- Malaria
- Keywords
- Plasmodium falciparum, malaria, merozoite surface protein-1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 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, United States Agency for International Development (USAID)
- Study start
- Jul 2003
- Primary completion
- Sep 2004 (actual)
- Study completion
- Jul 2005 (actual)
- First posted
- 28 Mar 2006 (estimated)
- Results
- Posted 31 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study tested the safety of a new malaria vaccine in adults in Mali, West Africa, and measured the ability of the vaccine to stimulate antibodies directed against the malaria protein that the vaccine is based on. Forty adults were randomly assigned to get either the experimental malaria vaccine or a rabies vaccine, for comparison.
Detailed description
The study was a randomized, controlled trial in which participants and clinical investigators were blinded to vaccine group assignment. Forty adults were randomized in a 1:1 ratio to receive either FMP1/AS02A or the control rabies vaccine. The aims of the control group were to account for baseline morbidity and the impact of seasonal malaria transmission on the dynamics of anti-MSP-1 antibodies, and to minimize bias in assessment of adverse events. Vaccines were given on a 0-, 1- and 2-month schedule. The first immunization was given in early July just as malaria transmission began; the second dose at the end of July as transmission was increasing; and the third dose in late August near the peak of malaria transmission intensity. Study day 90 was in October, shortly after transmission crests and when severe and uncomplicated malaria disease episodes peak, study day 180 was at the end of the malaria season, and study day 272 was at the height of the dry season. The final study follow-up on day 364 coincided with the beginning of the 2004 malaria season. Interim safety analyses were reviewed by an independent Safety Monitoring Committee before the second and third immunizations.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FMP1/AS02A Vaccine | Experimental | Biological: FMP1/AS02A500 uL of FMP1/AS02A is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle |
| Imovax Rabies Vaccine | Active comparator | Biological: Imovax Rabies Vaccine1 mL of Imovax Rabies Vaccine is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle |
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 dose of vaccine
- Written informed screening and study consent obtained from the participant before study start.
- Available and willing to participate in follow-up for the duration of study (12 months)
Key exclusion criteria (25 listed)
- Previous vaccination with an investigational malaria 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 dose of study vaccine, or planned use up to 30 days after the third dose.
- Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first vaccine dose. This will include oral steroids and inhaled steroids, but not topical steroids.
- Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of study vaccine(s) with the exception of tetanus toxoid.
- Previous vaccination with a vaccine containing MPL and/or QS-21 such as RTS,S.
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 |
|---|---|---|
| FMP1/AS02AFMP1 antigen contained 62.5 ug of lyophilized protein with 3.1 percent lactose as cryoprotectant. It's reconstituted in approx. 600 uL AS02A adjuvant manufactured by GSK. AS02A contains 50 ug MPL and 50ug QS21, 250uL of SB62 (oil/water emulsion) in phosphate buffered saline (PBS) per volume of 0.5 mL. All AS02A vials contained 0.65 to 0.75 mL of liquid. | Biological | FMP1/AS02A Vaccine |
| Imovax Rabies VaccineSterile, stable, freeze-dried suspension of rabies virus prepared from the strain PM-1503-3M, obtained from the Wistar Inst. in Philadelphia. Each 1 mL dose of vaccine contained 100 mg of human albumin, <150g of neomycin sulfate, and >2.5 IU of rabies antigen. | Biological | Imovax Rabies Vaccine |
Primary outcome
Number of Participants With Solicited Adverse Events by Immunization and Type
Time frame: Days 0, 1, 2, 3, 7, 30, 31, 32, 33, 37, 60, 61, 62, 63, 67
Number of participants with solicited adverse events by immunization and type (local, general and any) during each of the three eight-day follow-up periods after each vaccination (day of vaccination and post-vaccination days 1, 2, 3, and 7). Subjects were immunized on days 0, 30+7, and 60+7.
1 secondary outcome
Geometric Mean Titers for Anti-FMP1 Antibody
Time frame: Days 0, 14, 30, 44, 60, 74, 90, 180, 272, and 364
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16388879Stoute JA, Gombe J, Withers MR, Siangla J, McKinney D, Onyango M, Cummings JF, Milman J, Tucker K, Soisson L, Stewart VA, Lyon JA, Angov E, Leach A, Cohen J, Kester KE, Ockenhouse CF, Holland CA, Diggs CL, Wittes J, Heppner DG Jr; MSP-1 Malaria Vaccine Working Group. Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya. Vaccine. 2007 Jan 2;25(1):176-84. doi: 10.1016/j.vaccine.2005.11.037. Epub 2005 Dec 7.
- Background: PubMed 16356603Ockenhouse CF, Angov E, Kester KE, Diggs C, Soisson L, Cummings JF, Stewart AV, Palmer DR, Mahajan B, Krzych U, Tornieporth N, Delchambre M, Vanhandenhove M, Ofori-Anyinam O, Cohen J, Lyon JA, Heppner DG; MSP-1 Working Group. Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine. 2006 Apr 5;24(15):3009-17. doi: 10.1016/j.vaccine.2005.11.028. Epub 2005 Nov 28.
- Derived from this study: PubMed 18213374Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Kone AK, Guindo AB, Traore K, Dicko A, Sagara I, Sissoko MS, Baby M, Sissoko M, Diarra I, Niangaly A, Dolo A, Daou M, Diawara SI, Heppner DG, Stewart VA, Angov E, Bergmann-Leitner ES, Lanar DE, Dutta S, Soisson L, Diggs CL, Leach A, Owusu A, Dubois MC, Cohen J, Nixon JN, Gregson A, Takala SL, Lyke KE, Plowe CV. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial. PLoS One. 2008 Jan 23;3(1):e1465. doi: 10.1371/journal.pone.0001465.
- Individual participant dataSharing planned: No
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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, MD MPH principal investigator
University of Bamako Faculty of Medicine, Mali
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 FMP1/AS02A and Imovax Rabies Vaccine in people with 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 25 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 31 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 31 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?
Number of Participants With Solicited Adverse Events by Immunization and Type (time frame: Days 0, 1, 2, 3, 7, 30, 31, 32, 33, 37, 60, 61, 62, 63, 67). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00308061, which also lists 3 linked publications.
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 31 Jul 2017.