Plasmodium Falciparum InfectionPhase 1NCT03589794
rCSP/AP10-602 [GLA-LSQ] Vaccine Trial
A Phase 1 study testing AP10-602, Malaria challenge and rCSP in people with Plasmodium Falciparum Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This is a study to evaluate the safety, immunogenicity, and efficacy of a recombinant circumsporozoite protein (rCSP) malaria vaccine administered with and without AP 10-602 [Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)] adjuvant. 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?
- AP10-602, Malaria challenge and rCSP
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Dec 2018to 5 Jul 2022
- 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
- Healthy adults (males and non-pregnant, non-lactating females) between the ages of 18 and 45 years, inclusive
- Able and willing to participate for the duration of the study
- Able and willing to provide written (not proxy) informed consent
- Provides informed consent and correctly answers > / = 70 percent on the post consent quiz before any study procedures and is available for all study visits
- Females of childbearing potential and males must agree to practice highly effective contraception*
- Contraception must be practiced from 30 days before the time of enrollment until at least 30 days following the third vaccine dose for groups 1, 2 and 3, and the malaria challenge event for groups 4, 4B, 5 and 6 (such as double barrier methods (condoms plus foam or spermicide, diaphragm plus foam or spermicide), licensed intrauterine devices (IUDs), intravaginal or intra/transdermal or oral hormonal methods initiated at least 30 days before inoculation or challenge, documented surgical sterilization via tubal ligation the essure procedure or hysterectomy, abstinence or a vasectomized partner). The contraceptive method should remain unchanged throughout the study participation
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- Is in good health, as determined by vital signs (heart rate, blood pressure, oral temperature); medical history; laboratory values* that do not meet toxicity grading criteria, except when Grade 1 and clinically insignificant; and a physical examination
- Laboratory values include: hemoglobin, white blood cell count, platelet count, glucose (random), serum alanine aminotransferase (ALT), serum creatinine, urine protein and urine blood
- Agree not to travel to a malaria endemic region during the entire course of the trial
- Willing to avoid non-study related blood donation for the duration of participation in the study or until at least 1 year after receiving the last investigational vaccine, whichever is longer
- Able to understand and comply with planned study procedures including daily outpatient follow-up visits beginning 5 days after malaria challenge (groups 4, 4B, 5 and 6 only)
- Willing to avoid non-study related blood donation for 3 years following P. falciparum challenge (groups 4, 4B, 5 and 6 only)
Who cannot join
- Any history of malaria infection, or travel to a malaria endemic region within 6 months before first vaccination
- History of long-term residence (> / = 5 years) in an area known to have significant transmission of P. falciparum
- Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg)
- Positive sickle cell screening test or known hemoglobinopathy (groups 4, 4B, 5 and 6 only)
- Current or recent (within the last four weeks) treatment with parenteral or oral corticosteroids (intranasal or inhaled steroids are acceptable), or other immunosuppressive agents, or chemotherapy
- History of splenectomy
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- Participants who have a clinically significant (as determined by the PI or designee) baseline Grade 1 or greater toxicity, or any Grade 2 or greater toxicity (regardless of clinical significance) by the toxicity table, except hematuria > 1+ detected during menses for females*
- For females who are menstruating, urinalysis frequently tests positive for blood and is not an indicator of poor health status or increased risk.
- 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 for groups 1, 2, 3, 4, 4B and 5; or to the adjuvant for groups 1, 2, 4, 4B and 5
- History of acute or chronic medical conditions including, but not limited to, disorders of the liver, kidney, lung, heart, nervous system, or other metabolic or autoimmune/inflammatory conditions
- History of anaphylaxis or severe hypersensitivity reaction
- History of Guillain-Barre syndrome or severe adverse reaction to any vaccination
- Severe asthma, as defined by an emergency room visit or hospitalization within the last 12 months
- Pregnant or breastfeeding women or women who plan to become pregnant before day 115 in groups 1, 2 and 3; or before 30 days post-malaria challenge in groups 4, 4B, 5 and 6
- Concurrent participation in other investigational protocols prior to Day 141 or receipt of an investigational product within the previous 30 days
- Planned receipt of an investigational product within 28 days following the last vaccination dose or malaria challenge
- Any condition that, in the opinion of the investigator, would affect a participant's ability to understand or comply with the study protocol or would jeopardize a participant's safety or rights
- History of previous receipt of a candidate malaria vaccine or a vaccine containing the GLA-LSQ adjuvant
- Use or planned use of any drug with anti-malarial* activity 30 days before, or after malaria challenge (groups 4, 4B, 5 and 6 only)
- Medications with antimalarial activity include trimethoprim-sulfamethoxazole, azithromycin, erythromycin, tetracycline, doxycycline, minocycline, clindamycin, ciprofloxacin, levofloxacin, norfloxacin and rifampin
- Planned surgery 30 days before or after vaccination or malaria challenge
- History of drug or alcohol abuse within the last five years
- Receipt of blood or blood products in the previous six months or donation of a unit of blood within two months before screening
- History of schizophrenia, bipolar disorder or other psychiatric condition that makes study compliance difficult*
- Subjects with psychoses or history of suicide attempt or gesture in the 3 years before study entry, ongoing risk for suicide
- History of diabetes mellitus with the exception of pregnancy-induced diabetes that has resolved
- Has evidence of increased cardiovascular disease risk* (defined as > 10 percent, 5 year risk) as determined by the method of Gaziano (groups 4, 4B, 5 and 6 only)
- Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg / mm^2), reported diabetes status, and blood pressure
- Abnormal screening ECG* (groups 4, 4B, 5, and 6 only)
- Pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, non-sinus rhythm except isolated premature atrial or ventricular contractions, right of left bundle branch block, advanced A-V heart block (secondary or tertiary), QT/QTc interval > 450 ms
- Known hypersensitivity to mosquito bites, artemether-lumefantrine or atovaquone-proguanil (groups 4, 4B, 5 and 6 only)
- Anticipated medication use during the 28-day post-challenge period that are known to interact with artemether/lumefantrine or atovaquone/proguanil, such as cimetidine, metoclopramide, antacids, and kaolin (groups 4, 4B, 5 and 6 only)
- Previous participation in a CHMI study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, 21201-1509
About this study
Official title: A Phase I Challenge Study to Evaluate Safety, Immunogenicity, and Efficacy of a Malaria Vaccine (rCSP Adjuvanted With AP 10-602 [GLA-LSQ]), in Healthy Adults
This is a study to evaluate the safety, immunogenicity, and efficacy of a recombinant circumsporozoite protein (rCSP) malaria vaccine administered with and without AP 10-602 [Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)] adjuvant. 59 healthy adult, malaria naive volunteers aged 18 to 45 will receive vaccination with or without adjuvant (10 of those volunteers will receive rCSP alone) in five dose escalating groups. Each group will receive 3 vaccination doses total, with intramuscular (IM) injections on days 1, 29, and 85. A sixth group of 6 volunteers will receive no vaccinations and will participate as a control in a Controlled Human Malaria Infection (CHMI) challenge with two of the vaccinated groups. The study will be conducted at the Center for Vaccine Development (CVD) in Baltimore, Maryland. The patient participation duration is expected to be up to 886 days (up to 117 days for nonvaccination group). This study will test two hypotheses: (1) the rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will induce an immune response in a dose-dependent manner as measured by anti-CSP antibody titer via ELISA and (2) the rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will provide a minimum of 50% efficacy in vaccines compared to unvaccinated infectivity controls. The primary objective is to assess the safety and reactogenicity of candidate rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when administered intramuscularly on a 1, 29, and 85 day schedule (Groups 1-3, 4B, 5) and on a 1 and 490 day schedule (Group 4) to healthy malaria-naive adults aged 18-45 years.
Read the detailed description
This is a phase I, single-site, dose escalation study to evaluate the safety, immunogenicity, and efficacy of the recombinant circumsporozoite protein (rCSP) antigen malaria vaccine administered with and without AP 10-602 [Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)]. The study population will consist of 65 healthy male and female adults aged 18 to 45 years old and be conducted at the Center for Vaccine Development (CVD) in Baltimore, Maryland. 49 healthy, malaria-naïve volunteers will receive rCSP vaccination with AP 10-602 [GLA-LSQ] adjuvant. Ten volunteers will receive rCSP alone. Each dose-escalating group will receive 3 intramuscular (IM) total doses of vaccine on days 1, 29, and 85. Group 1 will receive a dose of 10 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) at each injection; Group 2 will receive 30 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ); Group 3 will receive 30 mcg rCSP without adjuvant; and Group 4 will receive 60 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ). The dose for Group 5 will depend on immunogenicity analysis from groups 1, 2 and 3. If immunogenicity analysis conducted 28 days post-2nd dose in Groups 1, 2 and 3 show promise (at least fourfold increase in geometric mean anti-CSP antibody or geometric mean anti-CSP titer of 20), the 10 volunteers in Group 5 will receive the lowest rCSP dose that gives this predefined immunogenic response ((either 10 or 30 mcg rCSP) + AP 10-602 [GLA-LSQ],]), otherwise, Group 5 will receive 60 mcg rCSP + AP 10-602 [GLA-LSQ]. Groups will be vaccinated in a stepwise manner following a "telescoped" design. A sixth group of 6 volunteers (Group 6) will receive no vaccinations and will be used as an infectivity control for a Controlled Human Malaria Infection (CHMI) challenge. Groups 4 and 5 will also undergo the CHMI challenge together, 28 days after the last vaccination. The patient participation duration is expected to be up to 886 days for Groups 1, 2, 3, 4, and 5; and up to 117 days for Group 6. This study will test two hypotheses: (1) the rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will induce an immune response in a dose-dependent manner as measured by anti-CSP antibody titer via ELISA and (2) the rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will provide a minimum of 50% efficacy in vaccines compared to unvaccinated infectivity controls. The primary objective is to assess the safety and reactogenicity of candidate rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when administered intramuscularly on a 1, 29, and 85 day schedule (Groups 1-3, 4B, 5) and on a 1 and 461 day schedule (Group 4) to healthy malaria-naive adults aged 18-45 years. The secondary objectives are to (1) assess immunogenicity of rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when administered intramuscularly on a 1, 29, and 85 day (Groups 1-3, 4B, 5) and on a 1 and 490 day schedule (Group 4) schedule and (2) to assess the preliminary efficacy of candidate rCSP/AP 10-602 [GLA-LSQ] malaria vaccine against infection with Plasmodium falciparum malaria (defined as P. falciparum asexual parasitemia or a delay in patency of infection > 2 days versus unimmunized infectivity controls) under Controlled Human Malaria Infection (CHMI).
- Conditions
- Plasmodium Falciparum Infection
- Being tested
- AP10-602, Malaria challenge, rCSP
- Keywords
- AP 10-602 [GLA-LSQ], Challenge, Healthy adults, Malaria, P. falciparum, rCSP, Vaccine
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AP10-602Other
Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ).
Malaria challengeOther
Exposure to mosquitoes infected with P. falciparum.
rCSPBiological
The rCSP malaria vaccine is a recombinant full-length P. falciparum circumsporozoite protein comprised of an amino terminus that binds heparin-sulfate proteoglycans, a four-amino-acid repeat region and a carboxy-terminus that contains a thrombospondin-like Type I region domain.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 10 subjects receive 10 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85. Receives: Other: AP10-602; Biological: rCSP |
| Group 2 | Experimental | 10 subjects receive 30 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85. Receives: Other: AP10-602; Biological: rCSP |
| Group 3 | Experimental | 10 subjects receive 30 mcg rCSP intramuscularly (IM) on days 1, 29 and 85. Receives: Biological: rCSP |
| Group 4 | Experimental | 9 subjects receive 60 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1 and 85. Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113. Receives: Other: AP10-602; Other: Malaria challenge; Biological: rCSP |
| Group 4B | Experimental | 10 subjects receive 60 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85. Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113. Receives: Other: AP10-602; Other: Malaria challenge; Biological: rCSP |
| Group 5 | Experimental | 10 subjects receive 10 mcg or 30 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85 if immunogenicity analysis conducted 28 days post-2nd dose in Groups 1, 2, and 3 show promise (at least fourfold increase in geometric mean anti-CSP antibody or geometric mean anti-CSP titer of 20). Otherwise, subjects will receive 60 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ). Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113. Receives: Other: AP10-602; Other: Malaria challenge; Biological: rCSP |
| Group 6 | Other | 6 subjects receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain. Receives: Other: Malaria challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects reporting Adverse Events of Special Interest (AESIs)
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Measured: Day 1 to Day 450
Number of subjects reporting serious adverse events (SAEs)
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Measured: Day 1 to Day 450
Number of subjects reporting serious adverse events (SAEs) considered related to vaccination
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Measured: Day 1 through Day 113
Number of subjects reporting severe (Grade 3) laboratory Adverse Events (AE) considered related to vaccination
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Measured: Day 1 through Day 92
Number of subjects reporting solicited local reactions
Measured: Day 1 through Day 92
Number of subjects reporting solicited systemic reactions
Measured: Day 1 through Day 92
Number of subjects reporting unsolicited adverse events (AEs) considered related to vaccination and that are severe (Grade 3)
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Measured: Day 1 through Day 113
Secondary outcomes (3)
Antibody titer against the malaria circumsporozoite antigen
Measured by Enzyme-linked Immunosorbent Assay (ELISA)
Measured: Day 1 through Day 574
Presence of P. falciparum asexual parasitemia following experimental malaria challenge
Measured: Day 118 to Day 141
Time to P. falciparum asexual parasitemia following experimental malaria challenge
Measured: Day 118 to Day 141
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2018
- Study start21 Dec 2018
- Primary completion5 Jul 2022
- Study completion5 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03589794
- Sponsor's protocol ID
- 13-0088
- Other IDs
- HHSN272201300022I
- Status last verified
- 19 Apr 2021
- First submitted
- 5 Jul 2018
- Last updated
- 10 Jul 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Friedman-Klabanoff DJ, Berry AA, Travassos MA, Shriver M, Cox C, Butts J, Lundeen JS, Strauss KA, Joshi S, Shrestha B, Mo AX, Nomicos EYH, Deye GA, Regules JA, Bergmann-Leitner ES, Pasetti MF, Laurens MB. Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge. J Infect Dis. 2024 Jun 14;229(6):1883-1893. doi: 10.1093/infdis/jiae062.
PubMed 38330357Friedman-Klabanoff DJ, Berry AA, Travassos MA, Cox C, Zhou Y, Mo AX, Nomicos EYH, Deye GA, Pasetti MF, Laurens MB. Low dose recombinant full-length circumsporozoite protein-based Plasmodium falciparum vaccine is well-tolerated and highly immunogenic in phase 1 first-in-human clinical testing. Vaccine. 2021 Feb 22;39(8):1195-1200. doi: 10.1016/j.vaccine.2020.12.023. Epub 2021 Jan 22.
PubMed 33494963
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Challenge Study to Evaluate Safety, Immunogenicity, and Efficacy of a Malaria Vaccine (rCSP Adjuvanted With AP 10-602 [GLA-LSQ]), in Healthy Adults
- ClinicalTrials.gov ID
- NCT03589794
- Acronym / sponsor ID
- 13-0088
- Conditions
- Plasmodium Falciparum Infection
- Keywords
- AP 10-602 [GLA-LSQ], Challenge, Healthy adults, Malaria, P. falciparum, rCSP, Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 21 Dec 2018 (actual)
- Primary completion
- 5 Jul 2022 (actual)
- Study completion
- 5 Jul 2022 (actual)
- First posted
- 18 Jul 2018 (actual)
- 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 is a study to evaluate the safety, immunogenicity, and efficacy of a recombinant circumsporozoite protein (rCSP) malaria vaccine administered with and without AP 10-602 [Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)] adjuvant. 59 healthy adult, malaria naive volunteers aged 18 to 45 will receive vaccination with or without adjuvant (10 of those volunteers will receive rCSP alone) in five dose escalating groups. Each group will receive 3 vaccination doses total, with intramuscular (IM) injections on days 1, 29, and 85. A sixth group of 6 volunteers will receive no vaccinations and will participate as a control in a Controlled Human Malaria Infection (CHMI) challenge with two of the vaccinated groups. The study will be conducted at the Center for Vaccine Development (CVD) in Baltimore, Maryland. The patient participation duration is expected to be up to 886 days (up to 117 days for nonvaccination group). This study will test two hypotheses: (1) the rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will induce an immune response in a dose-dependent manner as measured by anti-CSP antibody titer via ELISA and (2) the rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will provide a minimum of 50% efficacy in vaccines compared to unvaccinated infectivity controls. The primary objective is to assess the safety and reactogenicity of candidate rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when administered intramuscularly on a 1, 29, and 85 day schedule (Groups 1-3, 4B, 5) and on a 1 and 490 day schedule (Group 4) to healthy malaria-naive adults aged 18-45 years.
Detailed description
This is a phase I, single-site, dose escalation study to evaluate the safety, immunogenicity, and efficacy of the recombinant circumsporozoite protein (rCSP) antigen malaria vaccine administered with and without AP 10-602 [Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)]. The study population will consist of 65 healthy male and female adults aged 18 to 45 years old and be conducted at the Center for Vaccine Development (CVD) in Baltimore, Maryland. 49 healthy, malaria-naïve volunteers will receive rCSP vaccination with AP 10-602 [GLA-LSQ] adjuvant. Ten volunteers will receive rCSP alone. Each dose-escalating group will receive 3 intramuscular (IM) total doses of vaccine on days 1, 29, and 85. Group 1 will receive a dose of 10 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) at each injection; Group 2 will receive 30 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ); Group 3 will receive 30 mcg rCSP without adjuvant; and Group 4 will receive 60 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ). The dose for Group 5 will depend on immunogenicity analysis from groups 1, 2 and 3. If immunogenicity analysis conducted 28 days post-2nd dose in Groups 1, 2 and 3 show promise (at least fourfold increase in geometric mean anti-CSP antibody or geometric mean anti-CSP titer of 20), the 10 volunteers in Group 5 will receive the lowest rCSP dose that gives this predefined immunogenic response ((either 10 or 30 mcg rCSP) + AP 10-602 [GLA-LSQ],]), otherwise, Group 5 will receive 60 mcg rCSP + AP 10-602 [GLA-LSQ]. Groups will be vaccinated in a stepwise manner following a "telescoped" design. A sixth group of 6 volunteers (Group 6) will receive no vaccinations and will be used as an infectivity control for a Controlled Human Malaria Infection (CHMI) challenge. Groups 4 and 5 will also undergo the CHMI challenge together, 28 days after the last vaccination. The patient participation duration is expected to be up to 886 days for Groups 1, 2, 3, 4, and 5; and up to 117 days for Group 6. This study will test two hypotheses: (1) the rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will induce an immune response in a dose-dependent manner as measured by anti-CSP antibody titer via ELISA and (2) the rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will provide a minimum of 50% efficacy in vaccines compared to unvaccinated infectivity controls. The primary objective is to assess the safety and reactogenicity of candidate rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when administered intramuscularly on a 1, 29, and 85 day schedule (Groups 1-3, 4B, 5) and on a 1 and 461 day schedule (Group 4) to healthy malaria-naive adults aged 18-45 years. The secondary objectives are to (1) assess immunogenicity of rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when administered intramuscularly on a 1, 29, and 85 day (Groups 1-3, 4B, 5) and on a 1 and 490 day schedule (Group 4) schedule and (2) to assess the preliminary efficacy of candidate rCSP/AP 10-602 [GLA-LSQ] malaria vaccine against infection with Plasmodium falciparum malaria (defined as P. falciparum asexual parasitemia or a delay in patency of infection > 2 days versus unimmunized infectivity controls) under Controlled Human Malaria Infection (CHMI).
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Other: AP10-602, Biological: rCSP10 subjects receive 10 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85. |
| Group 2 | Experimental | Other: AP10-602, Biological: rCSP10 subjects receive 30 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85. |
| Group 3 | Experimental | Biological: rCSP10 subjects receive 30 mcg rCSP intramuscularly (IM) on days 1, 29 and 85. |
| Group 4 | Experimental | Other: AP10-602, Other: Malaria challenge, Biological: rCSP9 subjects receive 60 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1 and 85. Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113. |
| Group 4B | Experimental | Other: AP10-602, Other: Malaria challenge, Biological: rCSP10 subjects receive 60 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85. Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113. |
| Group 5 | Experimental | Other: AP10-602, Other: Malaria challenge, Biological: rCSP10 subjects receive 10 mcg or 30 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ) intramuscularly (IM) on days 1, 29 and 85 if immunogenicity analysis conducted 28 days post-2nd dose in Groups 1, 2, and 3 show promise (at least fourfold increase in geometric mean anti-CSP antibody or geometric mean anti-CSP titer of 20). Otherwise, subjects will receive 60 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ). Subjects will then receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain on day 113. |
| Group 6 | Other | Other: Malaria challenge6 subjects receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Healthy adults (males and non-pregnant, non-lactating females) between the ages of 18 and 45 years, inclusive
- Able and willing to participate for the duration of the study
- Able and willing to provide written (not proxy) informed consent
- Provides informed consent and correctly answers > / = 70 percent on the post consent quiz before any study procedures and is available for all study visits
- Females of childbearing potential and males must agree to practice highly effective contraception*
Key exclusion criteria (34 listed)
- Any history of malaria infection, or travel to a malaria endemic region within 6 months before first vaccination
- History of long-term residence (> / = 5 years) in an area known to have significant transmission of P. falciparum
- Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg)
- Positive sickle cell screening test or known hemoglobinopathy (groups 4, 4B, 5 and 6 only)
- Current or recent (within the last four weeks) treatment with parenteral or oral corticosteroids (intranasal or inhaled steroids are acceptable), or other immunosuppressive agents, or chemotherapy
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 |
|---|---|---|
| AP10-602Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ). | Other | Group 1, Group 2, Group 4, Group 4B, Group 5 |
| Malaria challengeExposure to mosquitoes infected with P. falciparum. | Other | Group 4, Group 4B, Group 5, Group 6 |
| rCSPThe rCSP malaria vaccine is a recombinant full-length P. falciparum circumsporozoite protein comprised of an amino terminus that binds heparin-sulfate proteoglycans, a four-amino-acid repeat region and a carboxy-terminus that contains a thrombospondin-like Type I region domain. | Biological | Group 1, Group 2, Group 3, Group 4, Group 4B, Group 5 |
Primary outcome
Number of subjects reporting Adverse Events of Special Interest (AESIs)
Time frame: Day 1 to Day 450
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Number of subjects reporting serious adverse events (SAEs)
Time frame: Day 1 to Day 450
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Number of subjects reporting serious adverse events (SAEs) considered related to vaccination
Time frame: Day 1 through Day 113
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Number of subjects reporting severe (Grade 3) laboratory Adverse Events (AE) considered related to vaccination
Time frame: Day 1 through Day 92
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
Number of subjects reporting solicited local reactions
Time frame: Day 1 through Day 92
Number of subjects reporting solicited systemic reactions
Time frame: Day 1 through Day 92
Number of subjects reporting unsolicited adverse events (AEs) considered related to vaccination and that are severe (Grade 3)
Time frame: Day 1 through Day 113
According to the Medical Dictionary for Regulatory Activities (MedDRA) classification
3 secondary outcomes
Antibody titer against the malaria circumsporozoite antigen
Time frame: Day 1 through Day 574
Presence of P. falciparum asexual parasitemia following experimental malaria challenge
Time frame: Day 118 to Day 141
Time to P. falciparum asexual parasitemia following experimental malaria challenge
Time frame: Day 118 to Day 141
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 10 Jul 2023.
- Derived from this study: PubMed 38330357Friedman-Klabanoff DJ, Berry AA, Travassos MA, Shriver M, Cox C, Butts J, Lundeen JS, Strauss KA, Joshi S, Shrestha B, Mo AX, Nomicos EYH, Deye GA, Regules JA, Bergmann-Leitner ES, Pasetti MF, Laurens MB. Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge. J Infect Dis. 2024 Jun 14;229(6):1883-1893. doi: 10.1093/infdis/jiae062.
- Derived from this study: PubMed 33494963Friedman-Klabanoff DJ, Berry AA, Travassos MA, Cox C, Zhou Y, Mo AX, Nomicos EYH, Deye GA, Pasetti MF, Laurens MB. Low dose recombinant full-length circumsporozoite protein-based Plasmodium falciparum vaccine is well-tolerated and highly immunogenic in phase 1 first-in-human clinical testing. Vaccine. 2021 Feb 22;39(8):1195-1200. doi: 10.1016/j.vaccine.2020.12.023. Epub 2021 Jan 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AP10-602, Malaria challenge and rCSP in people with Plasmodium Falciparum Infection, 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 12 inclusion and 34 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 10 Jul 2023. 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?
Number of subjects reporting Adverse Events of Special Interest (AESIs) (time frame: Day 1 to Day 450). The study lists 7 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 NCT03589794, which also lists 2 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 10 Jul 2023.