MalariaPhase 1/2NCT00385047
A Study to Determine Whether 2 Investigational Malaria Vaccines Are Safe, Protective Against Malaria in Adults
A Phase 1/2 study testing Group A FMP2.1/AS01B and Group B FMP2.1/AS02A in people with Malaria, run by U.S. Army Medical Research and Development Command at 1 site in United States.
Trial summary
The purpose of this study is to determine whether 2 investigational malaria vaccines are safe as well as protective against malaria in adults living in the United States Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Group A FMP2.1/AS01B and Group B FMP2.1/AS02A
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2006to Sep 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- A male or non-pregnant female 18 to 50 years of age (inclusive) at the time of screening
- Written informed consent obtained from the participant before screening procedures
- Free of clinically significant health problems as established by medical history and clinical examination before entering into the study*
- Available to participate for duration of study (approximately five months, not including screening)
- If the participant is female, she must be of non-childbearing potential, i.e., either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (e.g., intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant® or Depo-Provera®) during this study, have a negative pregnancy test at the time of each immunization, and must agree to continue such precautions for two months after completion of the immunization series and the malaria challenge.
- Prior to entry into this study, participants must score at least 80% correct on a short multiple-choice quiz that assesses their understanding of this study. If they do not score 80% on the initial quiz, the protocol information will be reviewed with them to ensure comprehension and they will have the opportunity to retest. Participants who fail the Comprehension Assessment for the second time will not be enrolled.
Who cannot join
- Prior receipt of an investigational malaria 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 during the study period, or receipt of investigational vaccine containing 3-D MPL and/or QS-21 at any time in the past (Have you received an experimental vaccine with a GSK adjuvant in the past?)
- Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of immunization. (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
- Chronic use of antibiotics with anti-malarial effects (e.g., tetracyclines for dermatologic patients, sulfa for recurrent urinary tract infections, etc.)
- Planned administration of a vaccine not foreseen by the study protocol 30 days prior to or after the first immunization
- History of malaria chemoprophylaxis within 60 days prior to immunization
Show all 30Show fewer
- Any history of malaria
- Known exposure to malaria within the previous 12 months
- Planned travel to malarious areas during the study period
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
- History of allergic disease or reactions to any vaccine
- Chronic or active neurologic disorders including seizures, excluding a single febrile seizure as a child
- History of splenectomy
- Acute disease at the time of enrollment (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., oral temperature < 37.5°C/99.5°F).
- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
- Personal medical histories including the following diagnoses: systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, scleroderma, vasculitis, and multiple sclerosis
- Seropositive for hepatitis B surface antigen or hepatitis C antibody
- Hepatomegaly, right upper quadrant abdominal pain or tenderness
- Elevated serum creatinine, defined in this study as greater than or equal to 1.7 mg/dL in males and 1.4 mg/dL in females
- Significant unexplained anemia: hematocrit < 35%
- Administration of immunoglobulins and/or any blood products within the three months preceding the first study immunization or planned administration during the study period
- Pregnant or lactating female or female who intends to become pregnant during the study
- Suspected or known current alcohol abuse as defined by the American Psychiatric Association in DSM IV (Diagnostic and Statistical Manual of Mental Disorders- 4th edition)
- Chronic or active illicit and/or intravenous drug use
- History of severe anaphylactic reactions to mosquito bites
- History of psoriasis (given its interaction with chloroquine)
- Any history of anaphylaxis in reaction to immunization
- History of allergy to nickel, imidazole or tetracycline group of antibiotics
- History of sickle cell disease or sickle cell trait
- Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Trials Center, Walter Reed Army Institute of Research
Silver Spring, Maryland, 20910
About this study
Official title: Phase I/IIa Study of the Safety, Immunogenicity and Preliminary Efficacy After Sporozoite Challenge of FMP2.1/AS01B and FMP2.1/AS02A Candidate Malaria Vaccines Administered Intramuscularly at Months 0, 1, and 2 in Malaria-naive Adults Living in the United States
The purpose of this study is to determine whether 2 investigational malaria vaccines are safe as well as protective against malaria in adults living in the United States
Read the detailed description
35 volunteers aged 18 to 50 years will be enrolled to receive one of 2 investigational malaria vaccines. The vaccines are made of a malaria protein FMP2.1 mixed in 2 different adjuvants (AS01B and AS02A). Five volunteers will get a small (10 µg) dose of FMP2.1/AS01B since this vaccine has not yet been in humans. If it is safe, then 15 volunteers will get 50 µg FMP2.1 in AS02A and 15 will get 50 µg FMP2.1 in AS01B. All vaccines are given IM in the deltoid of the non-dominant arm, every 1 month for 3 months. After vaccination, the subjects will follow up at clinical trials for evaluation of any adverse events.
20 vaccinees (10 from each 50 µg vaccine group) will undergo primary sporozoite challenge 14-30 days after dose 3 via bite of 5 malaria-infected mosquitoes. All subjects will have a blood slide prepared and read to check for asexual P. falciparum parasitemia at least once daily beginning day 5 post challenge. Beginning on day 10 post challenge, subjects will check into a designated hotel, where 24 hour evaluation and care will be available for 10 nights. After this hotel phase, there will be follow-up visits to ensure there are no late developments of malaria in those who have not fallen ill (and thus are considered protected).
Any subject who tests positive for malaria will be treated with chloroquine. Efficacy readouts are complete protection or significant delay in patency defined as >2 days than the median prepatent period for the 6 infectivity controls. These 6 controls receive no vaccine and are enrolled for malaria-challenge only in order to provide comparison group for vaccinated individuals.
- Conditions
- Malaria
- Being tested
- Group A FMP2.1/AS01B, Group B FMP2.1/AS02A
- Keywords
- malaria, vaccine, AMA-1 (apical membrane antigen-1), efficacy
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group A FMP2.1/AS01BBiological
Also called FMP 2.1 50 μg FMP2.1/AS01B
Group B FMP2.1/AS02ABiological
Also called FMP 2.1 50 μg FMP2.1/AS02A
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | FMP 2.1 50 μg FMP2.1/AS01B Receives: Biological: Group A FMP2.1/AS01B |
| Group B | Experimental | FMP 2.1 50 μg FMP2.1/AS02A Receives: Biological: Group B FMP2.1/AS02A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events
Measured: Up to 1 year
Secondary outcomes (5)
Anti-AMA-1 antibody titers during Immunization Phase
Measured: Up to 70 days
Anti-AMA-I antibody titers during Challenge Phase
Measured: Up to 90 days
Anti-AMA-I antibodies as percent parasite growth inhibition during Immunization Phase
Measured: Up to 70 days
Anti-AMA-I antibodies as percent parasite growth inhibition during Challenge Phase
Measured: Up to 90 days
Time to parasitemia development after primary challenge following administration of the FMP2.l/ASOIB and FMP2.l /AS02A
Measured: Up to 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2006 (estimated)
- Study startSep 2006
- Primary completionApr 2007
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- The PATH Malaria Vaccine Initiative (MVI), GlaxoSmithKline, United States Agency for International Development (USAID)
- Responsible party
- Sponsor
- Investigators
- Michele D. Spring, MD, M.S.P.H., Principal investigator, Walter Reed Army Institute of Research (WRAIR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00385047
- Sponsor's protocol ID
- WRAIR 1280
- Other IDs
- A-13949, ETrack Protocol No. 104936, MAL-045, #20060900
- Status last verified
- Jun 2015
- First submitted
- 4 Oct 2006
- Last updated
- 8 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Dutta S, Lalitha PV, Ware LA, Barbosa A, Moch JK, Vassell MA, Fileta BB, Kitov S, Kolodny N, Heppner DG, Haynes JD, Lanar DE. Purification, characterization, and immunogenicity of the refolded ectodomain of the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia coli. Infect Immun. 2002 Jun;70(6):3101-10. doi: 10.1128/IAI.70.6.3101-3110.2002.
PubMed 12011004Spring MD, Cummings JF, Ockenhouse CF, Dutta S, Reidler R, Angov E, Bergmann-Leitner E, Stewart VA, Bittner S, Juompan L, Kortepeter MG, Nielsen R, Krzych U, Tierney E, Ware LA, Dowler M, Hermsen CC, Sauerwein RW, de Vlas SJ, Ofori-Anyinam O, Lanar DE, Williams JL, Kester KE, Tucker K, Shi M, Malkin E, Long C, Diggs CL, Soisson L, Dubois MC, Ballou WR, Cohen J, Heppner DG Jr. Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A. PLoS One. 2009;4(4):e5254. doi: 10.1371/journal.pone.0005254. Epub 2009 Apr 23.
PubMed 19390585
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIa Study of the Safety, Immunogenicity and Preliminary Efficacy After Sporozoite Challenge of FMP2.1/AS01B and FMP2.1/AS02A Candidate Malaria Vaccines Administered Intramuscularly at Months 0, 1, and 2 in Malaria-naive Adults Living in the United States
- ClinicalTrials.gov ID
- NCT00385047
- Acronym / sponsor ID
- WRAIR 1280
- Conditions
- Malaria
- Keywords
- malaria, vaccine, AMA-1 (apical membrane antigen-1), efficacy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- The PATH Malaria Vaccine Initiative (MVI), GlaxoSmithKline, United States Agency for International Development (USAID)
- Study start
- Sep 2006
- Primary completion
- Apr 2007 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 6 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether 2 investigational malaria vaccines are safe as well as protective against malaria in adults living in the United States
Detailed description
35 volunteers aged 18 to 50 years will be enrolled to receive one of 2 investigational malaria vaccines. The vaccines are made of a malaria protein FMP2.1 mixed in 2 different adjuvants (AS01B and AS02A). Five volunteers will get a small (10 µg) dose of FMP2.1/AS01B since this vaccine has not yet been in humans. If it is safe, then 15 volunteers will get 50 µg FMP2.1 in AS02A and 15 will get 50 µg FMP2.1 in AS01B. All vaccines are given IM in the deltoid of the non-dominant arm, every 1 month for 3 months. After vaccination, the subjects will follow up at clinical trials for evaluation of any adverse events.
20 vaccinees (10 from each 50 µg vaccine group) will undergo primary sporozoite challenge 14-30 days after dose 3 via bite of 5 malaria-infected mosquitoes. All subjects will have a blood slide prepared and read to check for asexual P. falciparum parasitemia at least once daily beginning day 5 post challenge. Beginning on day 10 post challenge, subjects will check into a designated hotel, where 24 hour evaluation and care will be available for 10 nights. After this hotel phase, there will be follow-up visits to ensure there are no late developments of malaria in those who have not fallen ill (and thus are considered protected).
Any subject who tests positive for malaria will be treated with chloroquine. Efficacy readouts are complete protection or significant delay in patency defined as >2 days than the median prepatent period for the 6 infectivity controls. These 6 controls receive no vaccine and are enrolled for malaria-challenge only in order to provide comparison group for vaccinated individuals.
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 |
|---|---|---|
| Group A | Experimental | Biological: Group A FMP2.1/AS01BFMP 2.1 50 μg FMP2.1/AS01B |
| Group B | Experimental | Biological: Group B FMP2.1/AS02AFMP 2.1 50 μg FMP2.1/AS02A |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- A male or non-pregnant female 18 to 50 years of age (inclusive) at the time of screening
- Written informed consent obtained from the participant before screening procedures
- Free of clinically significant health problems as established by medical history and clinical examination before entering into the study*
- Available to participate for duration of study (approximately five months, not including screening)
- If the participant is female, she must be of non-childbearing potential, i.e., either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (e.g., intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant® or Depo-Provera®) during this study, have a negative pregnancy test at the time of each immunization, and must agree to continue such precautions for two months after completion of the immunization series and the malaria challenge.
Key exclusion criteria (30 listed)
- Prior receipt of an investigational malaria 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 during the study period, or receipt of investigational vaccine containing 3-D MPL and/or QS-21 at any time in the past (Have you received an experimental vaccine with a GSK adjuvant in the past?)
- Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of immunization. (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
- Chronic use of antibiotics with anti-malarial effects (e.g., tetracyclines for dermatologic patients, sulfa for recurrent urinary tract infections, etc.)
- Planned administration of a vaccine not foreseen by the study protocol 30 days prior to or after the first immunization
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 |
|---|---|---|
| Group A FMP2.1/AS01BAlso: FMP 2.1 50 μg FMP2.1/AS01B | Biological | Group A |
| Group B FMP2.1/AS02AAlso: FMP 2.1 50 μg FMP2.1/AS02A | Biological | Group B |
Primary outcome
Number of adverse events
Time frame: Up to 1 year
5 secondary outcomes
Anti-AMA-1 antibody titers during Immunization Phase
Time frame: Up to 70 days
Anti-AMA-I antibody titers during Challenge Phase
Time frame: Up to 90 days
Anti-AMA-I antibodies as percent parasite growth inhibition during Immunization Phase
Time frame: Up to 70 days
Anti-AMA-I antibodies as percent parasite growth inhibition during Challenge Phase
Time frame: Up to 90 days
Time to parasitemia development after primary challenge following administration of the FMP2.l/ASOIB and FMP2.l /AS02A
Time frame: Up to 1 Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
- Background: PubMed 12011004Dutta S, Lalitha PV, Ware LA, Barbosa A, Moch JK, Vassell MA, Fileta BB, Kitov S, Kolodny N, Heppner DG, Haynes JD, Lanar DE. Purification, characterization, and immunogenicity of the refolded ectodomain of the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia coli. Infect Immun. 2002 Jun;70(6):3101-10. doi: 10.1128/IAI.70.6.3101-3110.2002.
- Derived from this study: PubMed 19390585Spring MD, Cummings JF, Ockenhouse CF, Dutta S, Reidler R, Angov E, Bergmann-Leitner E, Stewart VA, Bittner S, Juompan L, Kortepeter MG, Nielsen R, Krzych U, Tierney E, Ware LA, Dowler M, Hermsen CC, Sauerwein RW, de Vlas SJ, Ofori-Anyinam O, Lanar DE, Williams JL, Kester KE, Tucker K, Shi M, Malkin E, Long C, Diggs CL, Soisson L, Dubois MC, Ballou WR, Cohen J, Heppner DG Jr. Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A. PLoS One. 2009;4(4):e5254. doi: 10.1371/journal.pone.0005254. Epub 2009 Apr 23.
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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.
Michele D. Spring, MD, M.S.P.H. principal investigator
Walter Reed Army Institute of Research (WRAIR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Group A FMP2.1/AS01B and Group B FMP2.1/AS02A in people with Malaria, run by U.S. Army Medical Research and Development Command at 1 site in United States.
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 6 inclusion and 30 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 8 Jun 2015. 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 United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 adverse events (time frame: Up to 1 year). 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 NCT00385047, which also lists 2 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 8 Jun 2015.