MalariaPhase 1NCT00114010
Experimental Vaccine for Malaria
A Phase 1 study testing AMA1/Alhydrogel in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will examine the safety and immune response of healthy adult volunteers to AMA1-C1, an experimental malaria vaccine developed by the NIAID. Malaria affects about 300 million to 500 million people worldwide each year, causing from 2 million to 3 million deaths. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Malaria
- What is being tested?
- AMA1/Alhydrogel
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2005to 22 Dec 2006
- Phase
- Phase 1
- 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
- No healthy volunteers
- Adult
Who may be able to join
- Males or females between 18 and 50 years, inclusive.
- Available for the duration of the trial (34 weeks)
- Willingness to participate in the study as evidenced by signing the informed consent document.
- Weighing at least 110 pounds.
Who cannot join
- Age less than 18 years because insufficient data are available in adults to judge potential risk in children.
- Pregnancy as determined by a positive urine Beta-hCG (if female).
- Participant unwilling to use reliable contraception methods (condoms or oral contraceptives) for the duration of the trial (if female).
- Currently lactating and breast-feeding (if female).
- Participant unwilling to undergo apheresis.
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
Show all 29Show fewer
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer to understand and cooperate with the study protocol.
- Laboratory evidence of liver disease (aspartate aminotransferase AST greater than the upper limit of normal of the testing laboratory and/or total bilirubin levels greater than the upper limits of normal of the testing laboratory).
- Laboratory evidence of renal disease (serum creatinine greater than the upper limit of normal of the testing laboratory).
- Laboratory evidence of hematologic disease (absolute neutrophil count less than 1,500/mm(3); hemoglobin less than the lower limit of normal of the testing laboratory, by sex; or platelet count less than 140,000/mm(3).
- Other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
- Participation in another investigational vaccine or drug trial within 30 days of enrolling in this study, or while this study is ongoing.
- Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
- History of a severe allergic reaction or anaphylaxis to drugs or foods.
- Asthma that has resulted in an emergency room visit or hospitalization within the last 6 months.
- Positive ELISA and confirmatory Western blot tests for HIV-1.
- Positive ELISA and standard confirmatory tests for HCV.
- Positive HBsAg by ELISA.
- Known immunodeficiency syndrome.
- Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of enrolling in this study or while the study is ongoing.
- Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
- History of a surgical splenectomy.
- Receipt of blood products within the past 6 months.
- Previous receipt of an investigational malaria vaccine.
- Receipt of antimalarial prophylaxis during the past 12 months.
- Prior malaria infection.
- Travel to a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study.
- History of a known allergy to nickel.
- History of known allergy to yeast.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Phase 1 Study of the Safety of Immunization of Naive Individuals With AMA1-C1/Alhydrogel [R], an Asexual Blood-Stage Vaccine for Plasmodium Falciparum Malaria, and the Effect of Immunization on Antigen-specific Memory and Plasma B Cells and T Cells
This study will examine the safety and immune response of healthy adult volunteers to AMA1-C1, an experimental malaria vaccine developed by the NIAID. Malaria affects about 300 million to 500 million people worldwide each year, causing from 2 million to 3 million deaths. Increasing drug resistance to the malaria parasite, as well as widespread resistance of mosquitoes (the insects that transmit the parasite) to pesticides are reducing the ability to control malaria through these strategies. A vaccine that could reduce illness and death from malaria would be a valuable new resource in the fight against this disease. Early tests of AMA1-C1 in 66 people in the United States and in Mali, West Africa, found no serious side effects of the vaccine. This study will test a shorter schedule of vaccinations with AMA1-C1 than that used in the previous studies.
Healthy volunteers between 18 and 50 years of age who weigh at least 110 pounds and with no travel to malaria endemic areas in the past 12 months may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, and a urine pregnancy test for women who are able to bear children.
Read more
Participants are randomly assigned to receive three injections of either the experimental malaria vaccine or a placebo (a solution that does not contain the vaccine) over a 2-month period. The shots are given in an upper arm muscle, each 1 month apart. On the day of each injection, participants give a history of symptoms since the last visit, have a brief physical examination and blood test and, for women, a blood or urine pregnancy test. After the injection, participants remain in the clinic 60 minutes for observation. In addition to the injections, participants undergo the following procedures:
- Record temperature and symptoms on a diary card daily for the first 7 days after each injection.
- Follow-up clinic visits 1, 3, 7 and 14 days after each shot to check for side effects. Blood samples are drawn before each injection and at each return clinic visit to check the safety and immune response to the vaccine.
- Have apheresis, a special procedure that separates certain components of the blood, 7 days after each injection to measure the function of germ-fighting blood cells. For this procedure, blood is drawn through a needle in an arm vein and directed into a machine that separates the different types of blood cells. The white cells are collected in a plastic ...
Read the detailed description
The study is a randomized, single-blinded (blinded to volunteers) placebo-controlled Phase 1 clinical trial in healthy adult volunteers designed to evaluate the safety and reactogenicity of a new malaria blood stage vaccine candidate, and to elucidate the immunogenicity of the antigen, AMA1-C1, formulated on Alhydrogel [R]. The trial will last 42 weeks. Volunteers will be recruited and screened, and those determined to be eligible will be enrolled in the study, based on the inclusion and exclusion criteria described in Section 4.0 in this protocol. After providing written informed consent the volunteers will be enrolled and randomly allocated to receive 80 microgram dose of AMA1-C1 formulated on Alhydrogel [R] (12 volunteers) or Alhydrogel [R] alone (6 volunteers) at 0, 1 and 2 months. After each injection, volunteers will be observed for 60 minutes for immediate reactions. Volunteers will return to the clinic on study days 1, 3, 7, and 14 following each injection for clinical assessment and collection of blood samples for evaluation of immune responses. Leukaphereses will be performed 7 days after the third vaccination to obtain peripheral blood mononuclear cells for B and T cell studies. Safety data for the cohort up to and including follow up day 14 after the first, second and third injection will be available for review by the Medical Monitor.
Immunogenicity of the vaccine will be assessed by standardized assays for antibody levels against AMA1-3D7 and AMA1-FVO, and an in vitro growth inhibition assay (GIA). The cellular basis of the immune responses will be evaluated by enumeration of relevant B and T cell subpopulations, including total and antigen-specific naive, memory and effector subpopulations specific for the antigens. The frequencies of B and T cells specific for the vaccine antigens in the group that received AMA1-C1/ Alhydrogel [R] will be compared to those in the group receiving Alhydrogel [R] alone. The total and antigen-specific cell frequencies in pre-immune (day 0) samples will serve as additional negative controls for the immunization. The goal of the study is to augment previously collected safety data for the 80 microgram antigen dose with a larger cohort, and to study the safety and immunogenicity of an accelerated vaccination schedule.
- Conditions
- Malaria
- Being tested
- AMA1/Alhydrogel
- Keywords
- B Cells, T Cells, Erythrocyte Stage, Antibody, Immunogenicity, Healthy Volunteer
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMA1/AlhydrogelDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2005 (estimated)
- Study start1 Apr 2005
- Primary completion22 Dec 2006
- Study completion22 Dec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Masking
- Single blind
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00114010
- Sponsor's protocol ID
- 050133
- Other IDs
- 05-I-0133
- Status last verified
- 19 Aug 2010
- First submitted
- 11 Jun 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Good MF, Kaslow DC, Miller LH. Pathways and strategies for developing a malaria blood-stage vaccine. Annu Rev Immunol. 1998;16:57-87. doi: 10.1146/annurev.immunol.16.1.57.
PubMed 9597124Narum DL, Thomas AW. Differential localization of full-length and processed forms of PF83/AMA-1 an apical membrane antigen of Plasmodium falciparum merozoites. Mol Biochem Parasitol. 1994 Sep;67(1):59-68. doi: 10.1016/0166-6851(94)90096-5.
PubMed 7838184Crewther PE, Culvenor JG, Silva A, Cooper JA, Anders RF. Plasmodium falciparum: two antigens of similar size are located in different compartments of the rhoptry. Exp Parasitol. 1990 Feb;70(2):193-206. doi: 10.1016/0014-4894(90)90100-q.
PubMed 2404781
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of the Safety of Immunization of Naive Individuals With AMA1-C1/Alhydrogel [R], an Asexual Blood-Stage Vaccine for Plasmodium Falciparum Malaria, and the Effect of Immunization on Antigen-specific Memory and Plasma B Cells and T Cells
- ClinicalTrials.gov ID
- NCT00114010
- Acronym / sponsor ID
- 050133
- Conditions
- Malaria
- Keywords
- B Cells, T Cells, Erythrocyte Stage, Antibody, Immunogenicity, Healthy Volunteer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 1 Apr 2005
- Primary completion
- 22 Dec 2006 (actual)
- Study completion
- 22 Dec 2006 (actual)
- First posted
- 13 Jun 2005 (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.
This study will examine the safety and immune response of healthy adult volunteers to AMA1-C1, an experimental malaria vaccine developed by the NIAID. Malaria affects about 300 million to 500 million people worldwide each year, causing from 2 million to 3 million deaths. Increasing drug resistance to the malaria parasite, as well as widespread resistance of mosquitoes (the insects that transmit the parasite) to pesticides are reducing the ability to control malaria through these strategies. A vaccine that could reduce illness and death from malaria would be a valuable new resource in the fight against this disease. Early tests of AMA1-C1 in 66 people in the United States and in Mali, West Africa, found no serious side effects of the vaccine. This study will test a shorter schedule of vaccinations with AMA1-C1 than that used in the previous studies.
Healthy volunteers between 18 and 50 years of age who weigh at least 110 pounds and with no travel to malaria endemic areas in the past 12 months may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, and a urine pregnancy test for women who are able to bear children.
Participants are randomly assigned to receive three injections of either the experimental malaria vaccine or a placebo (a solution that does not contain the vaccine) over a 2-month period. The shots are given in an upper arm muscle, each 1 month apart. On the day of each injection, participants give a history of symptoms since the last visit, have a brief physical examination and blood test and, for women, a blood or urine pregnancy test. After the injection, participants remain in the clinic 60 minutes for observation. In addition to the injections, participants undergo the following procedures:
- Record temperature and symptoms on a diary card daily for the first 7 days after each injection.
- Follow-up clinic visits 1, 3, 7 and 14 days after each shot to check for side effects. Blood samples are drawn before each injection and at each return clinic visit to check the safety and immune response to the vaccine.
- Have apheresis, a special procedure that separates certain components of the blood, 7 days after each injection to measure the function of germ-fighting blood cells. For this procedure, blood is drawn through a needle in an arm vein and directed into a machine that separates the different types of blood cells. The white cells are collected in a plastic ...
Detailed description
The study is a randomized, single-blinded (blinded to volunteers) placebo-controlled Phase 1 clinical trial in healthy adult volunteers designed to evaluate the safety and reactogenicity of a new malaria blood stage vaccine candidate, and to elucidate the immunogenicity of the antigen, AMA1-C1, formulated on Alhydrogel [R]. The trial will last 42 weeks. Volunteers will be recruited and screened, and those determined to be eligible will be enrolled in the study, based on the inclusion and exclusion criteria described in Section 4.0 in this protocol. After providing written informed consent the volunteers will be enrolled and randomly allocated to receive 80 microgram dose of AMA1-C1 formulated on Alhydrogel [R] (12 volunteers) or Alhydrogel [R] alone (6 volunteers) at 0, 1 and 2 months. After each injection, volunteers will be observed for 60 minutes for immediate reactions. Volunteers will return to the clinic on study days 1, 3, 7, and 14 following each injection for clinical assessment and collection of blood samples for evaluation of immune responses. Leukaphereses will be performed 7 days after the third vaccination to obtain peripheral blood mononuclear cells for B and T cell studies. Safety data for the cohort up to and including follow up day 14 after the first, second and third injection will be available for review by the Medical Monitor.
Immunogenicity of the vaccine will be assessed by standardized assays for antibody levels against AMA1-3D7 and AMA1-FVO, and an in vitro growth inhibition assay (GIA). The cellular basis of the immune responses will be evaluated by enumeration of relevant B and T cell subpopulations, including total and antigen-specific naive, memory and effector subpopulations specific for the antigens. The frequencies of B and T cells specific for the vaccine antigens in the group that received AMA1-C1/ Alhydrogel [R] will be compared to those in the group receiving Alhydrogel [R] alone. The total and antigen-specific cell frequencies in pre-immune (day 0) samples will serve as additional negative controls for the immunization. The goal of the study is to augment previously collected safety data for the 80 microgram antigen dose with a larger cohort, and to study the safety and immunogenicity of an accelerated vaccination schedule.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Single blind
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Males or females between 18 and 50 years, inclusive.
- Available for the duration of the trial (34 weeks)
- Willingness to participate in the study as evidenced by signing the informed consent document.
- Weighing at least 110 pounds.
Key exclusion criteria (29 listed)
- Age less than 18 years because insufficient data are available in adults to judge potential risk in children.
- Pregnancy as determined by a positive urine Beta-hCG (if female).
- Participant unwilling to use reliable contraception methods (condoms or oral contraceptives) for the duration of the trial (if female).
- Currently lactating and breast-feeding (if female).
- Participant unwilling to undergo apheresis.
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 |
|---|---|---|
| AMA1/Alhydrogel | Drug | – |
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 9597124Good MF, Kaslow DC, Miller LH. Pathways and strategies for developing a malaria blood-stage vaccine. Annu Rev Immunol. 1998;16:57-87. doi: 10.1146/annurev.immunol.16.1.57.
- Background: PubMed 7838184Narum DL, Thomas AW. Differential localization of full-length and processed forms of PF83/AMA-1 an apical membrane antigen of Plasmodium falciparum merozoites. Mol Biochem Parasitol. 1994 Sep;67(1):59-68. doi: 10.1016/0166-6851(94)90096-5.
- Background: PubMed 2404781Crewther PE, Culvenor JG, Silva A, Cooper JA, Anders RF. Plasmodium falciparum: two antigens of similar size are located in different compartments of the rhoptry. Exp Parasitol. 1990 Feb;70(2):193-206. doi: 10.1016/0014-4894(90)90100-q.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 AMA1/Alhydrogel in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 4 inclusion and 29 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 2 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 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 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?
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00114010, 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 2 Jul 2017.