MalariaPhase 1NCT00320658
Safety of and Immune Response to a Malaria Vaccine (MSP1 42-C1) With or Without CPG 7909 Adjuvant
A Phase 1 study testing MSP1 42-C1/Alhydrogel and CPG 7909 in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety of and immune response to a preventive malaria vaccine, MSP1 42-C1/Alhydrogel, in healthy adults. This study will also compare responses to two different doses of the malaria vaccine given with or without the adjuvant CPG 7909. 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?
- MSP1 42-C1/Alhydrogel and CPG 7909
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to Jul 2007
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Good general health
- Willing to be followed for the duration of the study
- Willing to use acceptable methods of contraception
Who cannot join
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may affect the ability of the volunteer to understand and cooperate with the study
- Liver disease (ALT greater than upper limit of normal [ULN])
- Kidney disease (serum creatinine greater than ULN)
- Hematologic disease (absolute neutrophil count of less than 1,500 cells/mm3; hemoglobin less than lower limit of normal, by sex; OR platelet count less than 140,000 mm3)
- Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
- Participation in another investigational vaccine or drug trial within 30 days of study entry or while this study is ongoing
Show all 26Show fewer
- Active drug or alcohol abuse causing medical, occupational, or family problems during the 12 months prior to study entry
- History of severe allergic reaction or anaphylaxis
- HIV-1 infected
- Hepatitis C virus infected
- Hepatitis B surface antigen positive
- Known immunodeficiency syndrome
- Use of corticosteroids or immunosuppressive drugs within 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded.
- Live vaccine within 4 weeks prior to study entry
- Killed vaccine within 2 weeks prior to study entry
- Blood products within 6 months prior to study entry
- Absence of spleen
- Previously received an investigational malaria vaccine
- Received antimalarial prophylaxis during the 12 months prior to study entry
- Received chloroquine or other aminoquinolines within 12 weeks of study entry
- Prior malaria infection
- Known allergy to nickel
- Pre-existing autoimmune or antibody-mediated disease. More information about this criterion can be found in the protocol.
- Any medical, psychiatric, social, or occupational condition or other responsibility that, in the opinion of the investigator, would interfere with the study
- Other condition that, in the opinion of the investigator, would affect the volunteer's participation in the study
- Pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Immunization Research, Johns Hopkins University, Bloomberg School of Public Health
Washington D.C., District of Columbia, 20037
About this study
Official title: Phase 1 Study of the Safety and Immunogenicity of MSP1 42-C1/Alhydrogel With and Without CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria
The purpose of this study is to determine the safety of and immune response to a preventive malaria vaccine, MSP1 42-C1/Alhydrogel, in healthy adults. This study will also compare responses to two different doses of the malaria vaccine given with or without the adjuvant CPG 7909.
Read the detailed description
In 2002, the World Health Organization reported a worldwide malaria incidence of approximately 300 million clinical cases annually, with approximately 1 million deaths attributed to malaria alone or in combination with other diseases. The parasite Plasmodium falciparum is responsible for the majority of these infections and deaths. During P. falciparum infection, liver cells are invaded by the parasite and asexual multiplication occurs. The liver cells burst, and tens of thousands of infectious particles called merozoites are released. A multiprotein complex on the surface of a merozoite is necessary for the merozoite to infect a blood cell. MSP1 42-C1 is a malaria vaccine that mimics MSP1 42, a protein in the multiprotein complex. By introducing this "decoy" form of MSP1 42, infection of additional blood cells may be blocked. The adjuvant CPG 7909 is known to elicit cell-mediated immunity, the arm of the immune system that defends the body against intracellular pathogens such as P. falciparum. This study will evaluate the safety and immunogenicity of MSP1 42-C1/Alhydrogel at two different doses in healthy adults. The vaccine will be given either alone or with CPG 7909.
This study will last at least 34 weeks. Participants will be randomly assigned to one of four groups:
- Group A participants will receive three injections of the lower dose of MSP1 42-C1/Alhydrogel.
- Group B participants will receive three injections of the lower dose of MSP1 42-C1/Alhydrogel and CPG 7909.
- Group C participants will receive three injections of the higher dose of MSP1 42-C1/Alhydrogel.
- Group D participants will receive three injections of the higher dose of MSP1 42-C1/Alhydrogel and CPG 7909.
Enrollment into Groups C and D will begin only after safety review of all participants in Groups A and B. All participants will receive their assigned injections at study entry, Week 4, and Week 8, and will be asked to return to the clinic the day after each vaccination for clinical evaluation. Participants will be asked to keep a diary for 6 days after each vaccination, taking note of their body temperatures and any side effects they experience. There will be a total of 18 study visits over 34 weeks. A clinical evaluation will occur at each visit. Blood collection, vital signs measurement, and urine collection will occur at selected visits.
- Conditions
- Malaria
- Being tested
- MSP1 42-C1/Alhydrogel, CPG 7909
- Keywords
- Plasmodium falciparum
- 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.
MSP1 42-C1/AlhydrogelBiological
Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses)
CPG 7909Biological
Adjuvant
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | 3 vaccinations with a dose of 40 mcg MSP1 42-C1/Alhydrogel given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm B. Receives: Biological: MSP1 42-C1/Alhydrogel |
| B | Experimental | 3 vaccinations with a dose of 40 mcg MSP1 42-C1/Alhydrogel and CPG7909 given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm A. Receives: Biological: MSP1 42-C1/Alhydrogel; Biological: CPG 7909 |
| C | Experimental | 3 vaccinations with a dose of 160 mcg MSP1 42-C1/Alhydrogel given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm D after review of the results from Arms A and B. Receives: Biological: MSP1 42-C1/Alhydrogel |
| D | Experimental | 3 vaccinations with a dose of 160 mcg MSP1 42-C1/Alhydrogel and CPG7909 given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm C after review of the results from Arms A and B. Receives: Biological: MSP1 42-C1/Alhydrogel; Biological: CPG 7909 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
Measured: Throughout study
Anti-MSP1 42 antibody concentration as measured by ELISA
Measured: At Day 70
Secondary outcomes (2)
To demonstrate that the addition of CPG 7909 improves the specific immune responses to MSP142-FVO and MSP142-3D7, as compared to MSP142-C1/Alhydrogel
Measured: At Day 70
To determine the dose of MSP142-C1/Alhydrogel + CPG 7909 that generates the highest serum antibody levels of MSP142-FVO and MSP142-3D7
Measured: At Day 70
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2006 (estimated)
- Study startMar 2006
- Primary completionJul 2007
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Investigators
- Anna Durbin, MD, Principal investigator, Johns Hopkins Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00320658
- Sponsor's protocol ID
- CIR 212
- Other IDs
- NIH Protocol Number 05-I-0240, WIRB Protocol Number 20051029
- Status last verified
- Jan 2008
- First submitted
- 1 May 2006
- Last updated
- 21 Jan 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Boutlis CS, Riley EM, Anstey NM, de Souza JB. Glycosylphosphatidylinositols in malaria pathogenesis and immunity: potential for therapeutic inhibition and vaccination. Curr Top Microbiol Immunol. 2005;297:145-85. doi: 10.1007/3-540-29967-x_5.
PubMed 16265905Hill AV. Pre-erythrocytic malaria vaccines: towards greater efficacy. Nat Rev Immunol. 2006 Jan;6(1):21-32. doi: 10.1038/nri1746.
PubMed 16493425Reed ZH, Friede M, Kieny MP. Malaria vaccine development: progress and challenges. Curr Mol Med. 2006 Mar;6(2):231-45. doi: 10.2174/156652406776055195.
PubMed 16515513Saul A, Lawrence G, Smillie A, Rzepczyk CM, Reed C, Taylor D, Anderson K, Stowers A, Kemp R, Allworth A, Anders RF, Brown GV, Pye D, Schoofs P, Irving DO, Dyer SL, Woodrow GC, Briggs WR, Reber R, Sturchler D. Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant. Vaccine. 1999 Aug 6;17(23-24):3145-59. doi: 10.1016/s0264-410x(99)00175-9.
PubMed 10462251Ellis RD, Martin LB, Shaffer D, Long CA, Miura K, Fay MP, Narum DL, Zhu D, Mullen GE, Mahanty S, Miller LH, Durbin AP. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naive adults. PLoS One. 2010 Jan 22;5(1):e8787. doi: 10.1371/journal.pone.0008787.
PubMed 20107498
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of the Safety and Immunogenicity of MSP1 42-C1/Alhydrogel With and Without CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria
- ClinicalTrials.gov ID
- NCT00320658
- Acronym / sponsor ID
- CIR 212
- Conditions
- Malaria
- Keywords
- Plasmodium falciparum
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Study start
- Mar 2006
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 3 May 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 the safety of and immune response to a preventive malaria vaccine, MSP1 42-C1/Alhydrogel, in healthy adults. This study will also compare responses to two different doses of the malaria vaccine given with or without the adjuvant CPG 7909.
Detailed description
In 2002, the World Health Organization reported a worldwide malaria incidence of approximately 300 million clinical cases annually, with approximately 1 million deaths attributed to malaria alone or in combination with other diseases. The parasite Plasmodium falciparum is responsible for the majority of these infections and deaths. During P. falciparum infection, liver cells are invaded by the parasite and asexual multiplication occurs. The liver cells burst, and tens of thousands of infectious particles called merozoites are released. A multiprotein complex on the surface of a merozoite is necessary for the merozoite to infect a blood cell. MSP1 42-C1 is a malaria vaccine that mimics MSP1 42, a protein in the multiprotein complex. By introducing this "decoy" form of MSP1 42, infection of additional blood cells may be blocked. The adjuvant CPG 7909 is known to elicit cell-mediated immunity, the arm of the immune system that defends the body against intracellular pathogens such as P. falciparum. This study will evaluate the safety and immunogenicity of MSP1 42-C1/Alhydrogel at two different doses in healthy adults. The vaccine will be given either alone or with CPG 7909.
This study will last at least 34 weeks. Participants will be randomly assigned to one of four groups:
- Group A participants will receive three injections of the lower dose of MSP1 42-C1/Alhydrogel.
- Group B participants will receive three injections of the lower dose of MSP1 42-C1/Alhydrogel and CPG 7909.
- Group C participants will receive three injections of the higher dose of MSP1 42-C1/Alhydrogel.
- Group D participants will receive three injections of the higher dose of MSP1 42-C1/Alhydrogel and CPG 7909.
Enrollment into Groups C and D will begin only after safety review of all participants in Groups A and B. All participants will receive their assigned injections at study entry, Week 4, and Week 8, and will be asked to return to the clinic the day after each vaccination for clinical evaluation. Participants will be asked to keep a diary for 6 days after each vaccination, taking note of their body temperatures and any side effects they experience. There will be a total of 18 study visits over 34 weeks. A clinical evaluation will occur at each visit. Blood collection, vital signs measurement, and urine collection will occur at selected visits.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Biological: MSP1 42-C1/Alhydrogel3 vaccinations with a dose of 40 mcg MSP1 42-C1/Alhydrogel given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm B. |
| B | Experimental | Biological: MSP1 42-C1/Alhydrogel, Biological: CPG 79093 vaccinations with a dose of 40 mcg MSP1 42-C1/Alhydrogel and CPG7909 given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm A. |
| C | Experimental | Biological: MSP1 42-C1/Alhydrogel3 vaccinations with a dose of 160 mcg MSP1 42-C1/Alhydrogel given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm D after review of the results from Arms A and B. |
| D | Experimental | Biological: MSP1 42-C1/Alhydrogel, Biological: CPG 79093 vaccinations with a dose of 160 mcg MSP1 42-C1/Alhydrogel and CPG7909 given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm C after review of the results from Arms A and B. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Good general health
- Willing to be followed for the duration of the study
- Willing to use acceptable methods of contraception
Key exclusion criteria (26 listed)
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may affect the ability of the volunteer to understand and cooperate with the study
- Liver disease (ALT greater than upper limit of normal [ULN])
- Kidney disease (serum creatinine greater than ULN)
- Hematologic disease (absolute neutrophil count of less than 1,500 cells/mm3; hemoglobin less than lower limit of normal, by sex; OR platelet count less than 140,000 mm3)
- Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
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 |
|---|---|---|
| MSP1 42-C1/AlhydrogelRecombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses) | Biological | A, B, C, D |
| CPG 7909Adjuvant | Biological | B, D |
Primary outcome
Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
Time frame: Throughout study
Anti-MSP1 42 antibody concentration as measured by ELISA
Time frame: At Day 70
2 secondary outcomes
To demonstrate that the addition of CPG 7909 improves the specific immune responses to MSP142-FVO and MSP142-3D7, as compared to MSP142-C1/Alhydrogel
Time frame: At Day 70
To determine the dose of MSP142-C1/Alhydrogel + CPG 7909 that generates the highest serum antibody levels of MSP142-FVO and MSP142-3D7
Time frame: At Day 70
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 21 Jan 2008.
- Background: PubMed 16265905Boutlis CS, Riley EM, Anstey NM, de Souza JB. Glycosylphosphatidylinositols in malaria pathogenesis and immunity: potential for therapeutic inhibition and vaccination. Curr Top Microbiol Immunol. 2005;297:145-85. doi: 10.1007/3-540-29967-x_5.
- Background: PubMed 16493425Hill AV. Pre-erythrocytic malaria vaccines: towards greater efficacy. Nat Rev Immunol. 2006 Jan;6(1):21-32. doi: 10.1038/nri1746.
- Background: PubMed 16515513Reed ZH, Friede M, Kieny MP. Malaria vaccine development: progress and challenges. Curr Mol Med. 2006 Mar;6(2):231-45. doi: 10.2174/156652406776055195.
- Background: PubMed 10462251Saul A, Lawrence G, Smillie A, Rzepczyk CM, Reed C, Taylor D, Anderson K, Stowers A, Kemp R, Allworth A, Anders RF, Brown GV, Pye D, Schoofs P, Irving DO, Dyer SL, Woodrow GC, Briggs WR, Reber R, Sturchler D. Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant. Vaccine. 1999 Aug 6;17(23-24):3145-59. doi: 10.1016/s0264-410x(99)00175-9.
- Derived from this study: PubMed 20107498Ellis RD, Martin LB, Shaffer D, Long CA, Miura K, Fay MP, Narum DL, Zhu D, Mullen GE, Mahanty S, Miller LH, Durbin AP. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naive adults. PLoS One. 2010 Jan 22;5(1):e8787. doi: 10.1371/journal.pone.0008787.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anna Durbin, MD principal investigator
Johns Hopkins Bloomberg School of Public Health
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 MSP1 42-C1/Alhydrogel and CPG 7909 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 3 inclusion and 26 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 21 Jan 2008. 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.
What does the primary outcome measure?
Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance (time frame: Throughout study). The study lists 2 primary outcomes in all. 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 NCT00320658, which also lists 5 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 21 Jan 2008.