Healthy VolunteerPhase 1NCT00340574
Improving the Efficacy of Experimental Malaria Vaccine AMA1-C1/Alhydrogel® (Registered Trademark)
A Phase 1 study testing AMA1-C1/Alhydrogel + CpG 7909 in people with Healthy Volunteer and HV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial summary
This study will evaluate the safety and efficacy of the experimental malaria vaccine AMA1-C1/Alhydrogel® (Registered Trademark) and determine whether a new, additional component of the vaccine may increase its effectiveness. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Healthy Volunteer, HV
- What is being tested?
- AMA1-C1/Alhydrogel + CpG 7909
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Mar 2005to 2 Jul 2008
- 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 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age between 18 and 45 years, inclusive.
- Good general health as a result of review of medical history and/or clinical tests.
- Available for the duration of the trial (34 weeks).
- Willingness to participate in the study as evidenced by signing the informed consent document.
Who cannot join
- Pregnancy as determined by a positive urine beta-hCG (if female) at any point during the study.
- Participant unwilling to use highly effective contraception methods (such as: abstinence, birth control pills or birth control patches or vaginal ring, diaphragm with spermicide, IUD (intrauterine device), condom with spermicide, progestin implant or injection, surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation), or a partner who has had a vasectomy for the duration of the trial (if female).
- Currently lactating and breast-feeding (if female).
- Evidence of clinically significant immunosuppressive, neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- 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 greater than 1.25 times the upper limit of normal of the testing laboratory).
Show all 25Show fewer
- 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/mm3; hemoglobin less than 0.9 times the lower limit of normal of the testing laboratory, by sex; or platelet count less than 140,000/mm3).
- 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 the 30 days of starting 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.
- Severe asthma (emergency room visit or hospitalization within the last 6 months).
- Serologic evidence of infection with HIV-1, HBV, or HCV.
- Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting 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.
- Pre-existing autoimmune or antibody mediated diseases including but not limited to: systemic lupus erythematosis, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia; or laboratory evidence of possible autoimmune disease determined by a positive anti-dsDNA titer, positive rheumatoid factor, proteinuria and/or a positive ANA.
- Chloroquine and related compounds within 12 weeks of study entry.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pi
Bethesda, Maryland, 20892
University of Rochester
Rochester, New York, 14642
About this study
Official title: Phase I Study of the Safety and Immunogenicity of AMA-1-C1/Alhydrogel + CPG 7909, An Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria
This study will evaluate the safety and efficacy of the experimental malaria vaccine AMA1-C1/Alhydrogel® (Registered Trademark) and determine whether a new, additional component of the vaccine may increase its effectiveness. Malaria is a debilitating and potentially fatal blood disease transmitted by a parasite found in certain mosquitoes. The AMA1-C1 vaccine has been designed to create an immune response against the parasite and prevent the disease. The purpose of the study is to determine whether the additional component-protein pieces known as CpG- improves the immune response to the vaccine without causing problematic side effects.
Volunteers must be healthy adults between 18 and 45 years old. Individuals who have had malaria in the past or have recently traveled to areas where malaria is endemic will be excluded from the study. Candidates will be screened with a physical examination, blood tests, and medical history.
Participants will be involved in a three-stage study. In the first stage, a group of participants will receive either a high dose of the vaccine alone or a low dose combined with the CpG protein. In the second stage, a different group of participants will receive a high dose of the vaccine alone or a high dose combined with CpG. In the third stage, a larger group of participants will receive a high dose of the vaccine alone or a high dose combined with CpG. The vaccine will be injected into the muscle of the upper arm, and all participants will receive three doses of the vaccine with 28 days between doses to monitor possible reactions and side effects. Participants will be monitored for 30 minutes after each injection and will record any symptoms they experience over the six days after receiving their dose. In addition, participants will be examined over the course of six months during and after the trial with physical exams and blood and urine tests.
Read the detailed description
Purpose: This study will evaluate the safety and immunogenicity of the experimental malaria vaccine AMA1-C1/Alhydrogel® (Registered Trademark), and the ability of the TLR-9 agonist CPG 7909 oligodexoynucleotide (ODN) to augment antibody response to the vaccine and alter the Th1/Th2 bias. The vaccine preparations to be studied contain an equal mixture of AMA1 from two different clones of Plasmodium falciparum (FVO and 3D7), both produced separately as recombinant proteins expressed by Pichia pastoris (PpAMA-1 FVO and PpAMA-1 3D7). Bulk PpAMA-1 antigens were purified from culture medium of transformed yeast grown in a 60L fermenter. The correctly folded PpAMA-1 was purified from this mixture by a combination of affinity, ionic, hydrophobic and gel filtration chromatography. Purified PpAMA-1 FVO and PpAMA-1 3D7 were subsequently mixed and adsorbed onto aluminum hydroxide gel (Alhydrogel® (Registered Trademark)). The CPG 7909 ODN formulation used in this study (CPG 7909) is manufactured by Coley Pharmaceutical Group. Subjects will be randomly assigned to receive Alhydrogel® (Registered Trademark) formulated vaccine with or without CPG 7909 in a point of use formulation.
Research Environment: The study will be conducted at the University of Rochester Vaccine and Treatment Evaluation Unit (VTEU).
Subjects: Subjects for this study will be healthy adults between the ages of 18 and 45 years with no history of malaria or of recent travel to malaria-endemic areas. Subjects will be enrolled in three consecutive dose-escalation cohorts with review by a Safety Monitoring Committee between cohorts.
Subject participation: Subjects will receive three vaccinations with the AMA1-C1/Alhydrogel® (Registered Trademark) vaccine formulated in Alhydrogel® (Registered Trademark) with or without CPG 7909 adjuvant over 2 months (0, 1, 2 months) by intramuscular (IM) injection. Subjects will have multiple blood samples obtained over the next 6 months.
Variables to be Investigated: Samples will be tested for binding antibody to AMA1 and for ability to inhibit the growth of plasmodia in vitro. In addition, antigen-specific activated B cells in peripheral blood will be enumerated, as well as the relative ratio of antigen-specific Th1-like and Th2-like T cells.
Risk/Benefits: The risks of participating in this study are those associated with administration of AMA1-C1/Alhydrogel® (Registered Trademark) and of CPG 7909, and include local pain, systemic inflammatory responses including fever and influenza-like symptoms, and induction of autoimmune responses. As with any other investigational vaccine, there are unknown risks. Subjects may derive no benefit from participation in this study. Development of effective vaccines to prevent malaria is an important societal benefit.
Confidentiality: Volunteers will have code numbers and will not be identified by name.
- Conditions
- Healthy Volunteer, HV
- Being tested
- AMA1-C1/Alhydrogel + CpG 7909
- Keywords
- Human, Clinical Trial, Mosquito, Healthy Volunteer, HV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMA1-C1/Alhydrogel + CpG 7909Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start8 Mar 2005
- Study completion2 Jul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteerStudies 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
- Enrolment
- 0 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00340574
- Sponsor's protocol ID
- 999905117
- Other IDs
- 05-I-N117
- Status last verified
- 2 Jul 2008
- First submitted
- 19 Jun 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Waters AP, Thomas AW, Deans JA, Mitchell GH, Hudson DE, Miller LH, McCutchan TF, Cohen S. A merozoite receptor protein from Plasmodium knowlesi is highly conserved and distributed throughout Plasmodium. J Biol Chem. 1990 Oct 15;265(29):17974-9.
PubMed 2211675
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 I Study of the Safety and Immunogenicity of AMA-1-C1/Alhydrogel + CPG 7909, An Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria
- ClinicalTrials.gov ID
- NCT00340574
- Acronym / sponsor ID
- 999905117
- Conditions
- Healthy Volunteer, HV
- Keywords
- Human, Clinical Trial, Mosquito, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 0 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 8 Mar 2005
- Study completion
- 2 Jul 2008
- First posted
- 21 Jun 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.
This study will evaluate the safety and efficacy of the experimental malaria vaccine AMA1-C1/Alhydrogel® (Registered Trademark) and determine whether a new, additional component of the vaccine may increase its effectiveness. Malaria is a debilitating and potentially fatal blood disease transmitted by a parasite found in certain mosquitoes. The AMA1-C1 vaccine has been designed to create an immune response against the parasite and prevent the disease. The purpose of the study is to determine whether the additional component-protein pieces known as CpG- improves the immune response to the vaccine without causing problematic side effects.
Volunteers must be healthy adults between 18 and 45 years old. Individuals who have had malaria in the past or have recently traveled to areas where malaria is endemic will be excluded from the study. Candidates will be screened with a physical examination, blood tests, and medical history.
Participants will be involved in a three-stage study. In the first stage, a group of participants will receive either a high dose of the vaccine alone or a low dose combined with the CpG protein. In the second stage, a different group of participants will receive a high dose of the vaccine alone or a high dose combined with CpG. In the third stage, a larger group of participants will receive a high dose of the vaccine alone or a high dose combined with CpG. The vaccine will be injected into the muscle of the upper arm, and all participants will receive three doses of the vaccine with 28 days between doses to monitor possible reactions and side effects. Participants will be monitored for 30 minutes after each injection and will record any symptoms they experience over the six days after receiving their dose. In addition, participants will be examined over the course of six months during and after the trial with physical exams and blood and urine tests.
Detailed description
Purpose: This study will evaluate the safety and immunogenicity of the experimental malaria vaccine AMA1-C1/Alhydrogel® (Registered Trademark), and the ability of the TLR-9 agonist CPG 7909 oligodexoynucleotide (ODN) to augment antibody response to the vaccine and alter the Th1/Th2 bias. The vaccine preparations to be studied contain an equal mixture of AMA1 from two different clones of Plasmodium falciparum (FVO and 3D7), both produced separately as recombinant proteins expressed by Pichia pastoris (PpAMA-1 FVO and PpAMA-1 3D7). Bulk PpAMA-1 antigens were purified from culture medium of transformed yeast grown in a 60L fermenter. The correctly folded PpAMA-1 was purified from this mixture by a combination of affinity, ionic, hydrophobic and gel filtration chromatography. Purified PpAMA-1 FVO and PpAMA-1 3D7 were subsequently mixed and adsorbed onto aluminum hydroxide gel (Alhydrogel® (Registered Trademark)). The CPG 7909 ODN formulation used in this study (CPG 7909) is manufactured by Coley Pharmaceutical Group. Subjects will be randomly assigned to receive Alhydrogel® (Registered Trademark) formulated vaccine with or without CPG 7909 in a point of use formulation.
Research Environment: The study will be conducted at the University of Rochester Vaccine and Treatment Evaluation Unit (VTEU).
Subjects: Subjects for this study will be healthy adults between the ages of 18 and 45 years with no history of malaria or of recent travel to malaria-endemic areas. Subjects will be enrolled in three consecutive dose-escalation cohorts with review by a Safety Monitoring Committee between cohorts.
Subject participation: Subjects will receive three vaccinations with the AMA1-C1/Alhydrogel® (Registered Trademark) vaccine formulated in Alhydrogel® (Registered Trademark) with or without CPG 7909 adjuvant over 2 months (0, 1, 2 months) by intramuscular (IM) injection. Subjects will have multiple blood samples obtained over the next 6 months.
Variables to be Investigated: Samples will be tested for binding antibody to AMA1 and for ability to inhibit the growth of plasmodia in vitro. In addition, antigen-specific activated B cells in peripheral blood will be enumerated, as well as the relative ratio of antigen-specific Th1-like and Th2-like T cells.
Risk/Benefits: The risks of participating in this study are those associated with administration of AMA1-C1/Alhydrogel® (Registered Trademark) and of CPG 7909, and include local pain, systemic inflammatory responses including fever and influenza-like symptoms, and induction of autoimmune responses. As with any other investigational vaccine, there are unknown risks. Subjects may derive no benefit from participation in this study. Development of effective vaccines to prevent malaria is an important societal benefit.
Confidentiality: Volunteers will have code numbers and will not be identified by name.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age between 18 and 45 years, inclusive.
- Good general health as a result of review of medical history and/or clinical tests.
- Available for the duration of the trial (34 weeks).
- Willingness to participate in the study as evidenced by signing the informed consent document.
Key exclusion criteria (25 listed)
- Pregnancy as determined by a positive urine beta-hCG (if female) at any point during the study.
- Participant unwilling to use highly effective contraception methods (such as: abstinence, birth control pills or birth control patches or vaginal ring, diaphragm with spermicide, IUD (intrauterine device), condom with spermicide, progestin implant or injection, surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation), or a partner who has had a vasectomy for the duration of the trial (if female).
- Currently lactating and breast-feeding (if female).
- Evidence of clinically significant immunosuppressive, neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- 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.
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-C1/Alhydrogel + CpG 7909 | 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 2211675Waters AP, Thomas AW, Deans JA, Mitchell GH, Hudson DE, Miller LH, McCutchan TF, Cohen S. A merozoite receptor protein from Plasmodium knowlesi is highly conserved and distributed throughout Plasmodium. J Biol Chem. 1990 Oct 15;265(29):17974-9.
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Screening Protocol
Pain
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.
2 sites 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-C1/Alhydrogel + CpG 7909 in people with Healthy Volunteer and HV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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 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 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 2 sites 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 NCT00340574, which also lists 1 linked publication.
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.