Dose Escalation, Randomized Controlled Trial to Evaluate the Safety, Immunogenicity and Efficacy of Intravenously Administered Attenuated Plasmodium Falciparum Sporozoite Vaccine (PfSPZ Vaccine) in Tanzanian Adults

Malaria Clinical Trial

Official title:

Phase 1, Dose Escalation, Randomized Controlled Trial to Evaluate the Safety, Immunogenicity and Efficacy of Intravenously Administered Attenuated Plasmodium Falciparum Sporozoite Vaccine (PfSPZ Vaccine) in Tanzanian Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02132299
• Other study ID #: BSPZV1
• Status: Completed
• Phase: Phase 1
• First received: April 29, 2014
• Last updated: April 25, 2016
• Start date: April 2014
• Est. completion date: August 2015

Study information

• Verified date: April 2016
• Source: Sanaria Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationTanzania: Food & Drug AdministrationTanzania: National Institute for Medical ResearchSwitzerland: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

This trial will evaluate whether relatively non-immune populations in endemic countries can effectively generate significant cellular and humoral immune responses that confer protection against P. falciparum infection after inoculation of aseptic, purified, vialed, metabolically active, non-replicating (live, radiation attenuated) Plasmodium falciparum sporozoites (PfSPZ Vaccine) administered intravenously (IV).

Description:

This is a single center, Phase 1, dose escalating, randomized, double blind, controlled trial. Seventy-three healthy male volunteers, aged 18 to 35 years will be recruited. The study will have 5 study groups that will include 49 volunteers who will be intravenously injected with PfSPZ Vaccine, 8 control volunteers who will receive normal saline and 16 additional control volunteers who will be recruited at the time of controlled human malaria infection (CHMI) at 3 and 24 weeks. The control volunteers will help better assess the occurrence of AEs compared to background disease patterns that occur in this tropical area, and the performance of the vaccine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: August 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Healthy male aged between 18 - 35 years.

• Good health status based on history and clinical examination.

• Long term or permanent resident in or near Dar-es-Salaam.

• Able and willing to complete the study visit schedule over the one year follow up period, including the hospitalizations required for protocol compliance.

• Able and willing to complete the informed consent process conducted in English.

• Demonstrate understanding of the study and procedures by answering 20 questions from the Protocol & Study Procedures Understanding Checklist correctly with a maximum of two attempts.

• Agrees to inform study doctor of medical conditions and contraindications for participation in the study.

• Agrees to provide contact information to the study team for a household member who will serve as an emergency contact during trial participation.

• Willing to be attended by a study doctor and take medications, which may be prescribed by a study doctor, during study participation.

• Reachable (24/7) by mobile phone during the whole study period.

• Agrees not to participate in another study during the study period.

• Agrees not to donate blood during the study period.

• Willing to undergo HIV, hepatitis B and hepatitis C testing.

• Willing to undergo controlled human malaria infection (CHMI).

Exclusion Criteria:

• History of malaria in the past 5 years.

• Positive for malaria by thick blood smear at screening.

• Plans to travel outside the Dar-es-Salaam or Coast Region in first 12 months of the study.

• Previous receipt of an investigational malaria vaccine.

• Antibodies to parasites or selected parasite protein(s) above acceptable cut off established for the site

• History of arrhythmias or prolonged QT-interval or other cardiac disease or clinically significant abnormalities in electrocardiogram (ECG) at screening.

• History or indication of a history of drug or alcohol abuse interfering with normal social function.

• Use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study enrollment (inhaled and topical corticosteroids are allowed).

• Ongoing condition that could interfere with the interpretation of the study results or compromise the health of the volunteer.

• History of diabetes mellitus or cancer.

• Body Mass Index (BMI) below 18 or above 30 kg/m2.

• Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis or electrolytes.

• Positive HIV, Hepatitis B virus or Hepatitis C virus tests.

• Participation in any other clinical study within 30 days prior to study enrollment.

• Known hypersensitivity, allergy, or other contra-indications to Coartem® or Malarone® including treatment taken by the volunteer that interferes with Coartem® or Malarone®.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia.

• Heterozygous or homozygous for sickle cell or homozygous for alpha thalassemia.

• Glucose-6-phosphate dehydrogenase deficiency

• Psychiatric condition that precludes compliance with the protocol; past or present psychoses; disorder requiring lithium; or within five years prior to enrollment, history of suicide plan or attempt.

• Any medical, psychiatric, social condition, or occupational reason that, in the judgment of the investigator, is a contraindication to protocol participation or impairs the volunteer's ability to give informed consent, increases the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.

• History of 3 or more other immunizations within the six months before administration of the first dose of vaccine.

• Clinically active tuberculosis

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Plasmodium Falciparum Malaria

Intervention

Biological:
• PfSPZ Vaccine
Aseptic, purified, vialed, metabolically active, non-replicating (live, radiation attenuated) cryopreserved Plasmodium falciparum sporozoites (PfSPZ)
• Normal Saline (Placebo)

• PfSPZ Challenge
Live, infectious, aseptic, purified, vialed, cryopreserved Plasmodium falciparum sporozoites (PfSPZ) for CHMI

Locations

Country	Name	City	State
Tanzania	Bagamoyo Research and Training Center, Ifakara Health Institute, Kingani Estate, PO Box 74	Bagamoyo

Sponsors (4)

Lead Sponsor	Collaborator
Sanaria Inc.	Ifakara Health Institute, Swiss Tropical & Public Health Institute, Tanzania Commission for Science and Technology

Country where clinical trial is conducted

Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory Endpoints - Immune Responses	Malaria specific immune responses in Groups 2, 3 and 4 as compared to the malaria naïve volunteers immunized at Vaccine Research Center of the NIH (protocol VRC 312) who received 1.35x10^5 PfSPZ/dose.	16 months	No
Primary	Safety and tolerability endpoints	Solicited local (IV site) and systemic AEs (AEs) observed in the 7 days after each vaccination and each CHMI.; Unsolicited AEs observed after the first vaccination until day 28 after the last vaccination for volunteers who do not undergo CHMI#1 (e.g. Group 1, those who do not complete the CHMI portion in Groups 2 and 3, and volunteers in Group 4).; Unsolicited AEs observed after the first vaccination until day 28 after the CHMI#1 for volunteers who undergo CHMI#1 3 weeks after the last vaccination (e.g. Groups 2 and 3).; Unsolicited AEs observed from day CHMI#2 (which occurs 24 weeks after the last vaccination) until day 28 after CHMI#2 (e.g. Groups 2-5).	Vaccination to CHMI (or 28 days after last vaccination); CHMI to 28 days after CHMI	Yes
Primary	Protective Efficacy after CHMI with PfSPZ Challenge (NF54) - CHMI Endpoints	Number of volunteers that remain parasite negative in each group through day 28 of follow up after CHMI with PfSPZ Challenge (NF54) IV inoculation.; Three weeks after their last immunization, volunteers in Groups 2 and 3 will under go their first CHMI with 3.2 x 10^3 PfSPZ Challenge (NF54) administered IV. Twenty-four weeks after the last immunization, volunteers from Groups 2 and 3 who underwent the first CHMI and did not become infected will have a second CHMI by IV injection of 3.2x10^3 PfSPZ Challenge (NF54). Volunteers in Groups 4 and 5 will only participate in the second CHMI assessment.; After CHMI, volunteers will be followed for evidence of infection with blood smears for 28 days.	CHMI to 28 days after CHMI	No
Secondary	Immune Responses after PfSPZ Vaccine	Cellular and humoral immune responses will be assessed in the vaccinated volunteers and controls (including central and effector memory responses and breadth and specificity of malaria antibodies).	16 months	No
Secondary	Protective effect of the high dose PfSPZ Vaccine regimen	Number of volunteers negative in Group 3 and Group 4 compared to Group 2 through day 28 of follow up after homologous PfSPZ Challenge (NF54) IV inoculation.	CHMI to day 28 after CHMI	No