MalariaPhase 1NCT00977899
Phase 1 Study of the Safety and Immunogenicity of a Malaria Transmission-blocking Pfs25-Pfs25 Conjugate Vaccine
A Phase 1 study testing Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate Vaccine in people with Malaria and Malaria Vaccines, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Trial summary
Background: Malaria, a disease transmitted by mosquitoes, affects millions of people with the highest frequency, morbidity, and mortality in infants and young children. Plasmodium falciparum and Plasmodium vivax, the most common and severe forms of malaria, have host- and stage-specific proteins that can induce… Read more about this study
- Who is it for?
- Ages 18 to 49 years
- Conditions the study is for
- Malaria, Malaria Vaccines, Plasmodium Falciparum Malaria
- What is being tested?
- Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate Vaccine
- Type of treatment
- Vaccines
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 20 Aug 2009to 5 Mar 2013
- 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 49 years
- All sexes
- No healthy volunteers
- Adult
- ELIGIBILITY AND EXCULUSION CRITERIA
Healthy adults, 18 to 49 years of age of either sex who do not have any of the following conditions will be eligible to participate:
- A chronic or progressive disease requiring chronic medication,
- History of surgical splenectomy or abnormal immune system,
- History of neurological symptoms or signs, or mental illness,
- Anaphylactic shock following administration of any vaccine or any other severe allergic reaction.,
- Women who are pregnant or intend to become pregnant during the vaccine study,
- Had malaria or received a malaria vaccine previously,
- Allergy to vaccine components or to nickel and yeast,
- Had cancer, HIV/AIDS, Hepatitis B or C, Guillain Barre Syndrome, chronic skin disease or have abnormal liver functions or blood counts.
About this study
Official title: Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate Vaccine
Background:
- Malaria, a disease transmitted by mosquitoes, affects millions of people with the highest frequency, morbidity, and mortality in infants and young children. Plasmodium falciparum and Plasmodium vivax, the most common and severe forms of malaria, have host- and stage-specific proteins that can induce immunity to the disease.
- Vaccines against stages that infect mosquitoes will prevent the spread of malaria. Researchers have developed a vaccine composed of a single protein, Pfs25, to induce antibodies in the human host that will be ingested by the mosquito and prevent the malaria parasite from reproducing and stop transmission of the disease. Because Pfs25 is present only in the mosquito, humans do not develop antibodies to this antigen even in endemic areas. Repeated injections of this vaccine may be necessary.
Read more
Objectives:
- To establish the safety and optimal dosage of a malaria vaccine developed with the Pfs25 protein.
Eligibility:
- Healthy adults between 18 and 49 years of age who have never had malaria or received a malaria vaccine.
Design:
- Two doses of Pfs25 conjugate (10 micrograms and 25 micrograms) will be evaluated in this study. Participants will receive only one of these doses in order to provide the best scientific data for evaluation.
- To determine eligibility, participants will provide a medical history and have a physical examination, and will provide blood and urine samples to test for HIV/AIDS, hepatitis, and other conditions that would prevent them from participating.
- Eligible participants will receive one injection of the vaccine. The injection will be followed 30 minutes later with a temperature reading and an inspection of the vaccine site.
- Upon leaving the clinic, participants will receive diary forms, a digital thermometer, a ruler, and instructions about how to take their temperature and to measure redness and swelling (if any) at the injection site. About 6 hours later, and daily for 3 days, participants will take their temperature at home and examine the injection site. Participants will be examined at the clinic at 48 to 72 hours and on day 7 after an injection. A blood sample will be taken 1 week after immunization. - Participants will receive a second and third injection of the same vaccine at 6-week intervals, and will follow the same recording procedure given above. Further blood samples will be taken at regular intervals for up to 12 months after the vaccination, as directed by the study researchers.
Read the detailed description
Malaria is a disease affecting millions of people in Africa, Asia, Central and South America . It has its highest frequency, morbidity, and mortality in infants and young children. For many reasons, a vaccine that would prevent this disease is sought.
Plasmodium falciparum and Plasmodium vivax, the most common and severe forms of malaria, have host and stage specific proteins that can induce immunity to disease caused by this pathogen. Surprisingly, vaccines against stages that infect mosquitos will prevent the spread of malaria (transmission-blocking). We have developed a vaccine composed of a single protein, denoted as Pfs25, to induce transmission-blocking antibodies in the human host. These transmission-blocking antibodies will be ingested by the mosquito and inactivate the sexual forms of the plasmodia (ookinetes) as they develop in the midgut of the mosquito. Because Pfs25 is present only in the mosquito, humans do not develop antibody to this antigen even in endemic areas. No antibodies were detected against Pfs25, a 21-kD protein expressed on zygotes and ookinetes of P. falciparum and known to be a sensitive target of transmission-blocking antibodies. Theoretically, frequent boosting with this antigen, as is required for the other experimental malarial vaccines, would be necessary.
Our investigational vaccine is based upon the following:
- Pfs25 is a low molecular weight protein and a poor immunogen. Bharti et al showed the protective action of antibodies to Pvs25 raised by intensive immunization of rabbits and mice (these regimes are not suitable for humans) to the recombinant protein. These findings have been confirmed;
- Transmission of Plasmodia to mosquitos is mediated by their ingestion of gametocytes in the human bloodstream. Within 10 minutes, these gametocytes transform into gametes in the midgut of the mosquito. The male gametocyte fertilizes the female to form a zygote. Twenty four hours later ookinetes pierce the epithelium of the midgut and differentiates into an oocyst. This cell type forms the sporozoite that lodges in the salivary gland and is the infective form injected by the mosquito into the human host. Pfs25 may also be involved in survival of the ookinete in the midgut and its transformation into the oocyst;
- The immunogenicity of poor immunogens is increased, especially in infants, by covalently binding them to medically-acceptable carrier proteins to form conjugates.
The Pfs25 was bound to itself by the synthetic scheme used for Haemophilus influenzae type b and other polysaccharides to proteins. The resultant conjugate was immunogenic and, unexpectedly, antibodies elicited by this vaccine continued to rise 3 months and 7 months after the second and third injections. The property of the Pfs25 conjugate to elicit long-lived antibody at high levels is unique to this construct. Our data from Pfs25 conjugate in mice suggest that administration of this vaccine to the whole population including infants along with their routine immunizations may be sufficient to elicit long-lived, effective transmission-blocking activity.
Our plan is to evaluate clinical lots of this conjugate for P. falciparum and for P. vivax, for their safety and immunogenicity in adults, children and infants, and then to establish a clinical site to test their efficacy.
- Conditions
- Malaria, Malaria Vaccines, Plasmodium Falciparum Malaria
- Being tested
- Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate Vaccine
- Keywords
- Plasmodium Falciparum, Alum Adsorbed, Ookinete Surface Protein, Malaria Vaccine, Healthy Volunteer, HV
- 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.
Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate VaccineBiological
What is being measured
The primary outcome is the main question the study is designed to answer.
Antibody
Secondary outcomes (1)
Transmission-blocking activity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2009 (estimated)
- Study start20 Aug 2009
- Primary completion5 Mar 2013
- Study completion5 Mar 2013
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.
- 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
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Investigators
- Feng-Ying C Lin, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00977899
- Sponsor's protocol ID
- 090213
- Other IDs
- 09-CH-0213
- Status last verified
- 5 Mar 2013
- First submitted
- 15 Sep 2009
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005 Mar 10;434(7030):214-7. doi: 10.1038/nature03342.
PubMed 15759000Fernando SD, Gunawardena DM, Bandara MR, De Silva D, Carter R, Mendis KN, Wickremasinghe AR. The impact of repeated malaria attacks on the school performance of children. Am J Trop Med Hyg. 2003 Dec;69(6):582-8.
PubMed 14740872Carter R, Mendis KN, Miller LH, Molineaux L, Saul A. Malaria transmission-blocking vaccines--how can their development be supported? Nat Med. 2000 Mar;6(3):241-4. doi: 10.1038/73062. No abstract available.
PubMed 10700212
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate Vaccine
- ClinicalTrials.gov ID
- NCT00977899
- Acronym / sponsor ID
- 090213
- Conditions
- Malaria, Malaria Vaccines, Plasmodium Falciparum Malaria
- Keywords
- Plasmodium Falciparum, Alum Adsorbed, Ookinete Surface Protein, Malaria Vaccine, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 20 Aug 2009
- Primary completion
- 5 Mar 2013 (actual)
- Study completion
- 5 Mar 2013 (actual)
- First posted
- 16 Sep 2009 (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.
Background:
- Malaria, a disease transmitted by mosquitoes, affects millions of people with the highest frequency, morbidity, and mortality in infants and young children. Plasmodium falciparum and Plasmodium vivax, the most common and severe forms of malaria, have host- and stage-specific proteins that can induce immunity to the disease.
- Vaccines against stages that infect mosquitoes will prevent the spread of malaria. Researchers have developed a vaccine composed of a single protein, Pfs25, to induce antibodies in the human host that will be ingested by the mosquito and prevent the malaria parasite from reproducing and stop transmission of the disease. Because Pfs25 is present only in the mosquito, humans do not develop antibodies to this antigen even in endemic areas. Repeated injections of this vaccine may be necessary.
Objectives:
- To establish the safety and optimal dosage of a malaria vaccine developed with the Pfs25 protein.
Eligibility:
- Healthy adults between 18 and 49 years of age who have never had malaria or received a malaria vaccine.
Design:
- Two doses of Pfs25 conjugate (10 micrograms and 25 micrograms) will be evaluated in this study. Participants will receive only one of these doses in order to provide the best scientific data for evaluation.
- To determine eligibility, participants will provide a medical history and have a physical examination, and will provide blood and urine samples to test for HIV/AIDS, hepatitis, and other conditions that would prevent them from participating.
- Eligible participants will receive one injection of the vaccine. The injection will be followed 30 minutes later with a temperature reading and an inspection of the vaccine site.
- Upon leaving the clinic, participants will receive diary forms, a digital thermometer, a ruler, and instructions about how to take their temperature and to measure redness and swelling (if any) at the injection site. About 6 hours later, and daily for 3 days, participants will take their temperature at home and examine the injection site. Participants will be examined at the clinic at 48 to 72 hours and on day 7 after an injection. A blood sample will be taken 1 week after immunization. - Participants will receive a second and third injection of the same vaccine at 6-week intervals, and will follow the same recording procedure given above. Further blood samples will be taken at regular intervals for up to 12 months after the vaccination, as directed by the study researchers.
Detailed description
Malaria is a disease affecting millions of people in Africa, Asia, Central and South America . It has its highest frequency, morbidity, and mortality in infants and young children. For many reasons, a vaccine that would prevent this disease is sought.
Plasmodium falciparum and Plasmodium vivax, the most common and severe forms of malaria, have host and stage specific proteins that can induce immunity to disease caused by this pathogen. Surprisingly, vaccines against stages that infect mosquitos will prevent the spread of malaria (transmission-blocking). We have developed a vaccine composed of a single protein, denoted as Pfs25, to induce transmission-blocking antibodies in the human host. These transmission-blocking antibodies will be ingested by the mosquito and inactivate the sexual forms of the plasmodia (ookinetes) as they develop in the midgut of the mosquito. Because Pfs25 is present only in the mosquito, humans do not develop antibody to this antigen even in endemic areas. No antibodies were detected against Pfs25, a 21-kD protein expressed on zygotes and ookinetes of P. falciparum and known to be a sensitive target of transmission-blocking antibodies. Theoretically, frequent boosting with this antigen, as is required for the other experimental malarial vaccines, would be necessary.
Our investigational vaccine is based upon the following:
- Pfs25 is a low molecular weight protein and a poor immunogen. Bharti et al showed the protective action of antibodies to Pvs25 raised by intensive immunization of rabbits and mice (these regimes are not suitable for humans) to the recombinant protein. These findings have been confirmed;
- Transmission of Plasmodia to mosquitos is mediated by their ingestion of gametocytes in the human bloodstream. Within 10 minutes, these gametocytes transform into gametes in the midgut of the mosquito. The male gametocyte fertilizes the female to form a zygote. Twenty four hours later ookinetes pierce the epithelium of the midgut and differentiates into an oocyst. This cell type forms the sporozoite that lodges in the salivary gland and is the infective form injected by the mosquito into the human host. Pfs25 may also be involved in survival of the ookinete in the midgut and its transformation into the oocyst;
- The immunogenicity of poor immunogens is increased, especially in infants, by covalently binding them to medically-acceptable carrier proteins to form conjugates.
The Pfs25 was bound to itself by the synthetic scheme used for Haemophilus influenzae type b and other polysaccharides to proteins. The resultant conjugate was immunogenic and, unexpectedly, antibodies elicited by this vaccine continued to rise 3 months and 7 months after the second and third injections. The property of the Pfs25 conjugate to elicit long-lived antibody at high levels is unique to this construct. Our data from Pfs25 conjugate in mice suggest that administration of this vaccine to the whole population including infants along with their routine immunizations may be sufficient to elicit long-lived, effective transmission-blocking activity.
Our plan is to evaluate clinical lots of this conjugate for P. falciparum and for P. vivax, for their safety and immunogenicity in adults, children and infants, and then to establish a clinical site to test their efficacy.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
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 |
|---|---|---|
| Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate Vaccine | Biological | – |
Primary outcome
Antibody
1 secondary outcome
Transmission-blocking activity
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 15759000Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005 Mar 10;434(7030):214-7. doi: 10.1038/nature03342.
- Background: PubMed 14740872Fernando SD, Gunawardena DM, Bandara MR, De Silva D, Carter R, Mendis KN, Wickremasinghe AR. The impact of repeated malaria attacks on the school performance of children. Am J Trop Med Hyg. 2003 Dec;69(6):582-8.
- Background: PubMed 10700212Carter R, Mendis KN, Miller LH, Molineaux L, Saul A. Malaria transmission-blocking vaccines--how can their development be supported? Nat Med. 2000 Mar;6(3):241-4. doi: 10.1038/73062. No abstract available.
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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.
Feng-Ying C Lin, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate Vaccine in people with Malaria and Malaria Vaccines, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: withdrawn, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Antibody. 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 NCT00977899, 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 5 Jul 2018.