Plasmodium Falciparum InfectionPhase 1NCT00371189
Adenovirus Vaccine for Malaria
A Phase 1 study testing Ad35.CS.01 Circumsporozoite Malaria Vaccine in people with Plasmodium Falciparum Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial summary
Malaria is caused by a parasite carried by a mosquito. Currently, there is no vaccine licensed to prevent malaria. The purpose of this study is to find the most effective and safest dose of an experimental vaccine for the treatment of malaria. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Falciparum Infection
- What is being tested?
- Ad35.CS.01 Circumsporozoite Malaria Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2007to Jun 2014
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of informed consent before any protocol procedures are performed.
- Males and non-pregnant females between the ages of 18 and 45 years, inclusive.
- Females and males must agree to practice adequate contraception until at least 28 days following their last immunization dose (including abstinence; hormonal contraception; condoms with spermicidal agents; post-menopausal; or surgical sterilization/vasectomy).
- Participants must agree to avoid high risk sexual behavior for exposure to human immunodeficiency virus (HIV).
- In good health as determined by screening medical history, physical examination (PE), and laboratory assessments.
- Willingness to comply with protocol requirements.
- Willingness to be contacted annually for five years for assessment of serious adverse events.
- Must have access to a cell phone.
Who cannot join
- Current or recent (within the last four weeks) treatment with parenteral, inhaled, or oral corticosteroids (intranasal steroids are acceptable), or other immunosuppressive agents, or chemotherapy.
- History of splenectomy.
- Abnormal screening laboratory values. Any abnormal screening value for any screening test will exclude the subject from the study. Abnormal screening labs will not be repeated with the exception of high glucose levels will be repeated at a fasting state.
- Detectible neutralizing antibody titer against adenovirus serotype 35.
- History of intravenous (IV) drug abuse.
- History of, or current medical, occupational, social or family problems as a result of alcohol or illicit drug use.
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- History of moderate to severe mental illness, as defined by symptoms interfering with social or occupational function or suicidal thoughts/attempts.
- History of receiving blood or blood products (such as blood transfusion, platelet transfusion, immunoglobulins, hyperimmune serum) in the previous 6 months.
- Vaccination with a live vaccine within the past 30 days or with a nonreplicating, inactivated, or subunit vaccine within the last 14 days.
- Known hypersensitivity to components of the vaccine.
- History of acute or chronic medical conditions including, but not limited to, disorders of the liver, kidney, lung, heart, or nervous system, or other metabolic or autoimmune/inflammatory conditions.
- History of coagulation defect or bleeding from (bruising at) multiple sites that cannot be linked to trauma or surgery.
- History of anaphylaxis or severe hypersensitivity reaction.
- Severe asthma, as defined by an emergency room visit or hospitalization within the last 12 months.
- Pregnant or breastfeeding women.
- Acute illness, including temperature greater than 100 degrees Fahrenheit within one week prior to vaccination.
- Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg).
- Concurrent participation in other investigational protocols or receipt of an investigational product within the previous 30 days or planned receipt of an investigational product within 28 days following the last immunization dose.
- Identification of any condition that, in the opinion of the investigator, would affect the ability of the subject to understand or comply with the study protocol or would jeopardize the safety or rights of a subject participating in the study.
- History of malignancy, including hematologic and skin cancers (except for a localized basal cell carcinoma), or known immunodeficiency syndrome.
- History of malaria infection or previous receipt of a malaria vaccine.
- History of travel to malaria-endemic area or receipt of antimalarial prophylaxis in the past 12 months.
- Planned travel to a malaria-endemic area prior to Visit 16 (Day 208).
- Pre-medication with analgesic or antipyretic agents in the 6 hours prior to vaccination, or planned medication with analgesic or antipyretic in the 24 hours following vaccination. This criterion should not preclude subjects receiving such medication if the need arises.
- Receipt of a recombinant adenovirus vector vaccine in a prior study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
Nashville, Tennessee, 37232-2573
Stanford University School of Medicine
Stanford, California, 94305-2200
About this study
Official title: A Phase I Randomized, Controlled, Dosage-Escalation Trial to Evaluate the Immunogenicity, Safety, and Reactogenicity of an Adenovirus Type 35 Based Circumsporozoite Malaria Vaccine in Healthy Adults 18 to 45 Years of Age
Malaria is caused by a parasite carried by a mosquito. Currently, there is no vaccine licensed to prevent malaria. The purpose of this study is to find the most effective and safest dose of an experimental vaccine for the treatment of malaria. Participants will include 72 healthy adults, ages18 to 45, enrolled at Vanderbilt University Medical Center and Stanford University. Volunteers will receive 3 doses of either the malaria vaccine or placebo (contains no vaccine) by injection into a muscle at 0, 1 and 6 months. Investigators will evaluate how the body responds to increasing dosage strengths of the vaccine. Study procedures include physical exam, multiple blood draws, and completion of a memory aid (diary). Each participant will be actively involved in the study for about 12 months. Then, an annual phone call will be made to check for any serious illness events for a period of 5 years.
Read the detailed description
Malaria currently represents one of the most prevalent infections in tropical and subtropical areas throughout the world. Each year, malaria affects around 300 million people and kills 1 to 3 million people in developing countries. The widespread occurrence and the growing incidence of malaria are a consequence of the increasing numbers of drug-resistant parasites and insecticide-resistant parasite vectors. Other factors include environmental and climatic changes, civil disturbances and increased mobility of populations. It is hypothesized that the Ad35.CS.01 vaccine will prevent the Plasmodium (P.) falciparum parasite, which causes malaria, from entering and developing within the liver of those who become infected. Ad35.CS.01 would therefore be expected to reduce malaria-attributable morbidity and mortality. The purpose of this phase I, randomized, controlled, dosage-escalation trial is to evaluate the immunogenicity, safety, and reactogenicity of an Adenovirus Type 35 based circumsporozoite malaria vaccine in 72 healthy adults, 18 to 45 years of age, in the United States. Subjects will be randomized in a 5:1 ratio to receive 3 doses of the Adenovirus Type 35 circumsporozoite malaria vaccine (Ad35.CS.01) or normal saline placebo control by the intramuscular route at 0, 1 and 6 months. The safety, reactogenicity, and immunogenicity of ascending dosages of the vaccine will be assessed. Fifteen subjects will receive vaccine at each of the following dosage levels: 10^8 viral particles (vp)/milliliters (ml), 10^9 vp/ml, 10^10 vp/ml and 10^11 vp/ml with 3 subjects receiving control at each of these dosage levels. Dosage escalation will proceed only after review of the safety data by the Safety Monitoring Committee of the prior dosage level. The primary objective is to assess the safety and reactogenicity of ascending dosages of Adenovirus Type 35 based circumsporozoite malaria vaccine among healthy subjects given in 3 intramuscular doses at 0, 1 and 6 months. The secondary objective is to evaluate the immunogenicity of the Adenovirus Type 35 based circumsporozoite malaria vaccine through performance of Humoral Immune Assays [ELISA (enzyme-linked immunosorbent assay)] for antibodies to circumsporozoite antigen and Adenovirus Neutralization Assay for neutralizing antibodies to Adenovirus type 35) and Cellular Immune Assays [enzyme-linked immunosorbent spot (ELISPOT) and Flow Cytometry] for circumsporozoite (CS)-specific cluster of differentiation (CD)4+ and CD8+ T cell responses.
- Conditions
- Plasmodium Falciparum Infection
- Being tested
- Placebo, Ad35.CS.01 Circumsporozoite Malaria Vaccine
- Keywords
- circumsporozoite, malaria, vaccine
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Normal saline.
Ad35.CS.01 Circumsporozoite Malaria VaccineBiological
Adenovirus Type 35 Circumsporozoite Malaria Vaccine (Ad35.CS.01); administered at 0, 1, and 6 months; dosage levels: 10^8 viral particles (vp)/mL, 10^9 vp/mL, 10^10 vp/mL and 10^11 vp/mL.
| Study group | Role | What they receive |
|---|---|---|
| Group C: Ad35.CS.01-10^10 vp/ml | Experimental | 15 subjects will receive dosage 10^10 vp/mL; 3 subjects will receive placebo. Receives: Drug: Placebo; Biological: Ad35.CS.01 Circumsporozoite Malaria Vaccine |
| Group D: Ad35.CS.01-10^11 vp/ml | Experimental | 15 subjects will receive dosage 10^11 vp/mL; 3 subjects will receive placebo. Receives: Drug: Placebo; Biological: Ad35.CS.01 Circumsporozoite Malaria Vaccine |
| Group A: Ad35.CS.01-10^8 vp/ml | Experimental | 15 subjects will receive dosage 10^8 vp/mL; 3 subjects will receive placebo. Receives: Drug: Placebo; Biological: Ad35.CS.01 Circumsporozoite Malaria Vaccine |
| Group B: Ad35.CS.01-10^9 vp/ml | Experimental | 15 subjects will receive dosage 10^9 vp/mL; 3 subjects will receive placebo. Receives: Drug: Placebo; Biological: Ad35.CS.01 Circumsporozoite Malaria Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and severity of local, systemic, and safety laboratory adverse events.
Measured: Enrollment through to Day 208
Secondary outcomes (3)
T cell responses against the malaria circumsporozoite antigen by enzyme-linked immunosorbent spot (ELISPOT) and flow cytometry.
Measured: Days 28, 56, 120, 180, 208.
Antibody titers against the malaria circumsporozoite antigen via enzyme-linked immunosorbent assay (ELISA).
Measured: Days 28, 56, 120, 180, 208.
Neutralizing antibody titers against Adenovirus type 35 by Adenovirus Neutralization Assay.
Measured: Days 28, 56, 120, 180, 208.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2006 (estimated)
- Study startJan 2007
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plasmodium Falciparum InfectionStudies 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, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00371189
- Sponsor's protocol ID
- 05-0050
- Other IDs
- N01AI80007C
- Status last verified
- Jun 2014
- First submitted
- 31 Aug 2006
- Last updated
- 22 Sep 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Randomized, Controlled, Dosage-Escalation Trial to Evaluate the Immunogenicity, Safety, and Reactogenicity of an Adenovirus Type 35 Based Circumsporozoite Malaria Vaccine in Healthy Adults 18 to 45 Years of Age
- ClinicalTrials.gov ID
- NCT00371189
- Acronym / sponsor ID
- 05-0050
- Conditions
- Plasmodium Falciparum Infection
- Keywords
- circumsporozoite, malaria, vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jan 2007
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 1 Sep 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.
Malaria is caused by a parasite carried by a mosquito. Currently, there is no vaccine licensed to prevent malaria. The purpose of this study is to find the most effective and safest dose of an experimental vaccine for the treatment of malaria. Participants will include 72 healthy adults, ages18 to 45, enrolled at Vanderbilt University Medical Center and Stanford University. Volunteers will receive 3 doses of either the malaria vaccine or placebo (contains no vaccine) by injection into a muscle at 0, 1 and 6 months. Investigators will evaluate how the body responds to increasing dosage strengths of the vaccine. Study procedures include physical exam, multiple blood draws, and completion of a memory aid (diary). Each participant will be actively involved in the study for about 12 months. Then, an annual phone call will be made to check for any serious illness events for a period of 5 years.
Detailed description
Malaria currently represents one of the most prevalent infections in tropical and subtropical areas throughout the world. Each year, malaria affects around 300 million people and kills 1 to 3 million people in developing countries. The widespread occurrence and the growing incidence of malaria are a consequence of the increasing numbers of drug-resistant parasites and insecticide-resistant parasite vectors. Other factors include environmental and climatic changes, civil disturbances and increased mobility of populations. It is hypothesized that the Ad35.CS.01 vaccine will prevent the Plasmodium (P.) falciparum parasite, which causes malaria, from entering and developing within the liver of those who become infected. Ad35.CS.01 would therefore be expected to reduce malaria-attributable morbidity and mortality. The purpose of this phase I, randomized, controlled, dosage-escalation trial is to evaluate the immunogenicity, safety, and reactogenicity of an Adenovirus Type 35 based circumsporozoite malaria vaccine in 72 healthy adults, 18 to 45 years of age, in the United States. Subjects will be randomized in a 5:1 ratio to receive 3 doses of the Adenovirus Type 35 circumsporozoite malaria vaccine (Ad35.CS.01) or normal saline placebo control by the intramuscular route at 0, 1 and 6 months. The safety, reactogenicity, and immunogenicity of ascending dosages of the vaccine will be assessed. Fifteen subjects will receive vaccine at each of the following dosage levels: 10^8 viral particles (vp)/milliliters (ml), 10^9 vp/ml, 10^10 vp/ml and 10^11 vp/ml with 3 subjects receiving control at each of these dosage levels. Dosage escalation will proceed only after review of the safety data by the Safety Monitoring Committee of the prior dosage level. The primary objective is to assess the safety and reactogenicity of ascending dosages of Adenovirus Type 35 based circumsporozoite malaria vaccine among healthy subjects given in 3 intramuscular doses at 0, 1 and 6 months. The secondary objective is to evaluate the immunogenicity of the Adenovirus Type 35 based circumsporozoite malaria vaccine through performance of Humoral Immune Assays [ELISA (enzyme-linked immunosorbent assay)] for antibodies to circumsporozoite antigen and Adenovirus Neutralization Assay for neutralizing antibodies to Adenovirus type 35) and Cellular Immune Assays [enzyme-linked immunosorbent spot (ELISPOT) and Flow Cytometry] for circumsporozoite (CS)-specific cluster of differentiation (CD)4+ and CD8+ T cell responses.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group C: Ad35.CS.01-10^10 vp/ml | Experimental | Drug: Placebo, Biological: Ad35.CS.01 Circumsporozoite Malaria Vaccine15 subjects will receive dosage 10^10 vp/mL; 3 subjects will receive placebo. |
| Group D: Ad35.CS.01-10^11 vp/ml | Experimental | Drug: Placebo, Biological: Ad35.CS.01 Circumsporozoite Malaria Vaccine15 subjects will receive dosage 10^11 vp/mL; 3 subjects will receive placebo. |
| Group A: Ad35.CS.01-10^8 vp/ml | Experimental | Drug: Placebo, Biological: Ad35.CS.01 Circumsporozoite Malaria Vaccine15 subjects will receive dosage 10^8 vp/mL; 3 subjects will receive placebo. |
| Group B: Ad35.CS.01-10^9 vp/ml | Experimental | Drug: Placebo, Biological: Ad35.CS.01 Circumsporozoite Malaria Vaccine15 subjects will receive dosage 10^9 vp/mL; 3 subjects will receive placebo. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Provision of informed consent before any protocol procedures are performed.
- Males and non-pregnant females between the ages of 18 and 45 years, inclusive.
- Females and males must agree to practice adequate contraception until at least 28 days following their last immunization dose (including abstinence; hormonal contraception; condoms with spermicidal agents; post-menopausal; or surgical sterilization/vasectomy).
- Participants must agree to avoid high risk sexual behavior for exposure to human immunodeficiency virus (HIV).
- In good health as determined by screening medical history, physical examination (PE), and laboratory assessments.
Key exclusion criteria (25 listed)
- Current or recent (within the last four weeks) treatment with parenteral, inhaled, or oral corticosteroids (intranasal steroids are acceptable), or other immunosuppressive agents, or chemotherapy.
- History of splenectomy.
- Abnormal screening laboratory values. Any abnormal screening value for any screening test will exclude the subject from the study. Abnormal screening labs will not be repeated with the exception of high glucose levels will be repeated at a fasting state.
- Detectible neutralizing antibody titer against adenovirus serotype 35.
- History of intravenous (IV) drug abuse.
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 |
|---|---|---|
| PlaceboNormal saline. | Drug | Group A: Ad35.CS.01-10^8 vp/ml, Group B: Ad35.CS.01-10^9 vp/ml, Group C: Ad35.CS.01-10^10 vp/ml, Group D: Ad35.CS.01-10^11 vp/ml |
| Ad35.CS.01 Circumsporozoite Malaria VaccineAdenovirus Type 35 Circumsporozoite Malaria Vaccine (Ad35.CS.01); administered at 0, 1, and 6 months; dosage levels: 10^8 viral particles (vp)/mL, 10^9 vp/mL, 10^10 vp/mL and 10^11 vp/mL. | Biological | Group A: Ad35.CS.01-10^8 vp/ml, Group B: Ad35.CS.01-10^9 vp/ml, Group C: Ad35.CS.01-10^10 vp/ml, Group D: Ad35.CS.01-10^11 vp/ml |
Primary outcome
Frequency and severity of local, systemic, and safety laboratory adverse events.
Time frame: Enrollment through to Day 208
3 secondary outcomes
T cell responses against the malaria circumsporozoite antigen by enzyme-linked immunosorbent spot (ELISPOT) and flow cytometry.
Time frame: Days 28, 56, 120, 180, 208.
Antibody titers against the malaria circumsporozoite antigen via enzyme-linked immunosorbent assay (ELISA).
Time frame: Days 28, 56, 120, 180, 208.
Neutralizing antibody titers against Adenovirus type 35 by Adenovirus Neutralization Assay.
Time frame: Days 28, 56, 120, 180, 208.
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 22 Sep 2014.
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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.
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 Ad35.CS.01 Circumsporozoite Malaria Vaccine in people with Plasmodium Falciparum Infection, 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 8 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 22 Sep 2014. 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.
What does the primary outcome measure?
Frequency and severity of local, systemic, and safety laboratory adverse events. (time frame: Enrollment through to Day 208). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Sep 2014.