- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03589794
rCSP/AP10-602 [GLA-LSQ] Vaccine Trial
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21201-1509
- University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
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)
Exclusion Criteria:
- 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
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1
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.
|
Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ).
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.
|
Experimental: Group 2
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.
|
Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ).
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.
|
Experimental: Group 3
10 subjects receive 30 mcg rCSP intramuscularly (IM) on days 1, 29 and 85.
|
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.
|
Experimental: Group 4
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.
|
Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ).
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.
Exposure to mosquitoes infected with P. falciparum.
|
Experimental: Group 4B
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.
|
Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ).
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.
Exposure to mosquitoes infected with P. falciparum.
|
Experimental: Group 5
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.
|
Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ).
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.
Exposure to mosquitoes infected with P. falciparum.
|
Other: Group 6
6 subjects receive CHMI challenge with P. falciparum parasites of the NF54/3D7 strain.
|
Exposure to mosquitoes infected with P. falciparum.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Day 1 to Day 450
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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
|
Day 1 to Day 450
|
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
|
Day 1 through Day 113
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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
|
Day 1 through Day 92
|
Number of subjects reporting solicited local reactions
Time Frame: Day 1 through Day 92
|
Day 1 through Day 92
|
|
Number of subjects reporting solicited systemic reactions
Time Frame: Day 1 through Day 92
|
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
|
Day 1 through Day 113
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Antibody titer against the malaria circumsporozoite antigen
Time Frame: Day 1 through Day 574
|
Measured by Enzyme-linked Immunosorbent Assay (ELISA)
|
Day 1 through Day 574
|
Presence of P. falciparum asexual parasitemia following experimental malaria challenge
Time Frame: Day 118 to Day 141
|
Day 118 to Day 141
|
|
Time to P. falciparum asexual parasitemia following experimental malaria challenge
Time Frame: Day 118 to Day 141
|
Day 118 to Day 141
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 13-0088
- HHSN272201300022I
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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