Experimental PfSPZ Vaccine in Adults Without Malaria
|First Received Date ICMJE||September 24, 2011|
|Last Updated Date||May 2, 2013|
|Start Date ICMJE||September 2011|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||The primary objectives of the study are related to the safety and tolerability of the vaccine at the 4 dosage levels when administered IV.|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01441167 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||The secondary objectives are related to PfSPZ vaccine-mediated protection against Plasmodium falciparum (Pf) challenge at the 3 higher dosage levels.|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Experimental PfSPZ Vaccine in Adults Without Malaria|
|Official Title ICMJE||VRC 312: A Phase 1, Open-Label, Dose-Escalation Clinical Trial With Experimental Challenge to Evaluate Intravenous Administration of the PfSPZ Vaccine in Malaria-Naive Adults|
- To test the safety and effectiveness of the PfSPZ vaccine.
- Healthy volunteers between 18 to 45 years of age.
All participants from any group who receive a malaria challenge will be treated promptly for malaria when it develops.
Study Design: VRC 312 is the second study of the PfSPZ Vaccine and the first study to evaluate intravenous (IV) administration of this vaccine. The study is designed as an openlabel evaluation of the safety, tolerability, immunogenicity and protective efficacy of the vaccine at successively higher dosages (2000; 7500; 30,000 and 135,000 SPZ per injection) administered by the IV route. The 3 higher dosages will be evaluated for protection against a malaria challenge after 4 to 6 vaccinations. Control subjects are included in the malaria challenge. The primary objectives of the study are related to the safety and tolerability of the vaccine at the 4 dosage levels when administered IV; the secondary objectives are related to PfSPZ vaccine-mediated protection against Plasmodium falciparum (Pf) challenge at the 3 higher dosage levels; and the exploratory objectives are related to the immunogenicity of the PfSPZ Vaccine and defining an immune correlate of protection.
Product Description: The investigational PfSPZ Vaccine is manufactured by Sanaria, Inc (Rockville, MD) under current Good Manufacturing Practices (cGMP). The vaccine consists of a suspension of purified, metabolically-active, radiation-attenuated cryopreserved Pf sporozoites formulated in cryoprotectant and dispensed in a 0.5 mL screw-cap vial containing a 20 mcL aliquot at a concentration of 150,000 sporozoites (+/-50,000 sporozoites) per 20 mcL. The vaccine is stored in the vapor-phase of liquid nitrogen (LNVP) at -140 to -196 degrees C. The PfSPZ Vaccine is delivered by Sanaria, Inc. to the clinical investigators and diluted in phosphate buffered saline (PBS) with 1% human serum albumin (HSA) to achieve the correct dosage.
Subjects: Healthy subjects, 18-45 years old, who are malaria-naive. The fewest number of subjects needed to complete the study as originally designed was 51; however, with inclusion of study provisions for back-up challenge subjects enrollment of additional vaccinees and options for rechallenge, as added by protocol amendments, the amended accrual allowance is 68 subjects.
Study Plan: Subjects will be enrolled in a step-wise, dose-escalation manner with stringent stopping rules designed for subject safety. The first 12 subjects will be allocated as the pilot subjects that comprise Groups 1, 2a, 3a, 4a; each of which includes 3 pilot subjects. For the pilot subjects, the 1st vaccination (V1) and 2nd vaccination (V2) will be administered no faster than one per pilot subject every 2 hours.
Before administration of the first dose to the subsequent pilot Group (dose escalation), at least 5 weeks of cumulative safety data for the pilot subjects in a dosage group (i.e., 1 week past 2nd vaccination) must be submitted to the Safety Monitoring Committee (SMC) and the FDA, and protocol-specified approval received for the dose escalation.
Subjects in vaccine Groups 2, 3, 4 and the Group 5 controls will be challenged by exposure to Anopheles stephensi mosquitoes infected with Pf sporozoites in a controlled setting, followed by testing for parasitemia at specified intervals through up to 28 days post-challenge. To facilitate intensive daily close monitoring of clinical status and blood smears, 11 overnight stays are required from days 7-18 post-challenge. Subjects who develop blood stage P. falciparum infection will be treated as soon as a case is identified by the protocol criteria. Following treatment, a subject will be considered cured when 2 consecutive daily blood smears are negative. After establishing cure, blood smear checks may end and the subject may discontinue overnight stays.
Challenges occur at specified timepoints in which each challenge includes vaccine recipients and control subjects. Rechallenge options to assess for durability of protective responses and further evaluation of immune correlates of protection are included in the protocol.
Study Duration: The study will take approximately 18 months to complete. The period of follow-up for each vaccinated subject is through at least 24 weeks after the last vaccination. The total duration on study will vary depending upon the schedule assignment and whether or not the subject participates in a rechallenge. The Group 5 (challenge only) subjects and rechallenged subjects will be followed through 8 weeks after last challenge.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Intervention ICMJE||Biological: PfSPZ
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
A volunteer must meet all of the following criteria to be included:
A volunteer will be excluded if one or more of the following conditions apply:
|Ages||18 Years to 45 Years|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01441167|
|Other Study ID Numbers ICMJE||110257, 11-I-0257|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||July 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP