Safety, Tolerability and Efficacy of PfSPZ Vaccine Against Heterologous CHMI in US Malaria naïve Adults

NCT04966871 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: USSPZV6
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double blind, placebo-controlled, single site, trial of a condensed regimen of PfSPZ Vaccine administered on Days 1, 8 and 29 by direct venous inoculation (DVI) to assess safety, tolerability, immunogenicity and vaccine efficacy (VE) against heterologous controlled human malaria infection (CHMI) conducted at varying time intervals after the third immunization (14, 42 or 70 days). The trial is designed to simulate pre-deployment immunization of military personnel. Prior studies with this regimen show high level protection (\>80%) against CHMI at 21 days, but the onset and duration of protection have not been fully defined.

Conditions

Malaria

Keywords

PfSPZ Vaccine; Malaria; Plasmodium falciparum; Controlled human malaria infection

Outcome Measures

Primary Outcomes (5)

• Vaccine efficacy (VE) of PfSPZ Vaccine against Pf malaria in adults

  VE computed as one minus the estimated risk ratio for Pf infection (parasitemia) detected by qRT-PCR beginning 7 days after CHMI and censoring subjects at 28 days in the "modified Intention to Treat" (mITT) population

  7-28 days after CHMI

• Safety and tolerability of 3 doses of 9.0x10^5 PfSPZ of PfSPZ Vaccine- solicited AEs

  The differences in proportions of vaccinees compared to controls experiencing related solicited adverse events after vaccination.

  Day of first immunization until 8 weeks post CHMI

• Safety and tolerability of 3 doses of 9.0x10^5 PfSPZ of PfSPZ Vaccine- solicited AEs

  The differences in proportions of vaccinees compared to controls experiencing related unsolicited adverse events after vaccination.

  Day of first immunization until 8 weeks post CHMI

• Safety and tolerability of 3 doses of 9.0x10^5 PfSPZ of PfSPZ Vaccine- SAEs

  The differences in proportions of vaccinees compared to controls experiencing related serious adverse events (SAEs) after vaccination.

  Day of first immunization until 8 weeks post CHMI

• Safety and tolerability of 3 doses of 9.0x10^5 PfSPZ of PfSPZ Vaccine- Lab abnormalities

  The differences in proportions of vaccinees compared to controls experiencing related laboratory abnormalities after vaccination.

  Day of first immunization until 8 weeks post CHMI

Secondary Outcomes (3)

• Antibody responses to PfCSP post-immunization/CHMI and correlation with protection in vaccinees vs controls

  2 weeks post Vaccination 2 until 4 weeks post CHMI

• Antibody responses to PfCSP post-immunization/CHMI and correlation with protection in protected vs unprotected vaccinees

  2 weeks post Vaccination 2 until 4 weeks post CHMI

• VE between different groups with CHMI at 14, 42 or 70 days after Vaccination 3

  Day of first immunization until 8 weeks post CHMI

Study Arms (6)

Group A (PfSPZ Vaccine; PfSPZ Challenge 7G8)

EXPERIMENTAL

14 volunteers will receive 3 doses of 9 x 10\^5 PfSPZ Vaccine on days 1, 8, 29. Controlled human malaria infection (CHMI) with PfSPZ Challenge (7G8) will be administered on day 14 by DVI injection.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (7G8) for CHMI

Group B (PfSPZ Vaccine; PfSPZ Challenge 7G8)

EXPERIMENTAL

14 volunteers will receive 9 x 10\^5 PfSPZ Vaccine on days 1, 8, 29. Controlled human malaria infection (CHMI) with PfSPZ Challenge (7G8) will be administered on day 42 by DVI injection.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (7G8) for CHMI

Group C (PfSPZ Vaccine; PfSPZ Challenge 7G8)

EXPERIMENTAL

14 volunteers will receive 9 x 10\^5 PfSPZ Vaccine on days 1, 8, 29. Controlled human malaria infection (CHMI) with PfSPZ Challenge (7G8) will be administered on day 70 by DVI injection.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (7G8) for CHMI

Group A controls (Saline; PfSPZ Challenge 7G8)

PLACEBO COMPARATOR

4 volunteers will receive Normal Saline (NS) as placebo on days 1, 8, 29. Controlled human malaria infection (CHMI) with PfSPZ Challenge (7G8) will be administered on day 14 by DVI injection.

Biological: PfSPZ Challenge (7G8) for CHMI; Other: Normal Saline

Group B controls (Saline; PfSPZ Challenge 7G8)

PLACEBO COMPARATOR

4 volunteers will receive Normal Saline (NS) as placebo on days 1, 8, 29. Controlled human malaria infection (CHMI) with PfSPZ Challenge (7G8) will be administered on day 42 by DVI injection.

Biological: PfSPZ Challenge (7G8) for CHMI; Other: Normal Saline

Group C controls (Saline; PfSPZ Challenge 7G8)

PLACEBO COMPARATOR

4 volunteers will receive Normal Saline (NS) as placebo on days 1, 8, 29. Controlled human malaria infection (CHMI) with PfSPZ Challenge (7G8) will be administered on day 70 by DVI injection.

Biological: PfSPZ Challenge (7G8) for CHMI; Other: Normal Saline

Interventions

PfSPZ Vaccine BIOLOGICAL

Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Group A (PfSPZ Vaccine; PfSPZ Challenge 7G8); Group B (PfSPZ Vaccine; PfSPZ Challenge 7G8); Group C (PfSPZ Vaccine; PfSPZ Challenge 7G8)

PfSPZ Challenge (7G8) for CHMI BIOLOGICAL

Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain 7G8

Group A (PfSPZ Vaccine; PfSPZ Challenge 7G8); Group A controls (Saline; PfSPZ Challenge 7G8); Group B (PfSPZ Vaccine; PfSPZ Challenge 7G8); Group B controls (Saline; PfSPZ Challenge 7G8); Group C (PfSPZ Vaccine; PfSPZ Challenge 7G8); Group C controls (Saline; PfSPZ Challenge 7G8)

Normal Saline OTHER

normal saline placebo control

Group A controls (Saline; PfSPZ Challenge 7G8); Group B controls (Saline; PfSPZ Challenge 7G8); Group C controls (Saline; PfSPZ Challenge 7G8)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults (male or non-pregnant female) 18 to 50 years of age
• Able and willing to participate for the duration of the study
• Able and willing to provide written (not proxy) informed consent
• Physical examination and laboratory results without clinically significant findings
• Individuals of childbearing potential must agree to use effective means of birth control (e.g. oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) during the entire study. Female participants with a history of surgical or chemical sterilization (e.g. tubal ligation, hysterectomy, other) must provide written documentation of the procedure from a health care provider
• Willing to refrain from blood donation for 3 years following CHMI
• Agree not to travel to a malaria endemic region during the entire course of the trial

You may not qualify if:

• A history of malaria infection within 2 years prior to study participation or travel to a malaria endemic region within six months prior to first immunization
• Receipt of a malaria vaccine in a prior clinical trial
• History of a splenectomy or sickle cell disease
• History of a neurologic disorder (including non-febrile seizures or complex febrile seizures) or formal history of migraine headache
• Current use of systemic immunosuppressant pharmacotherapy
• Receipt of a live vaccine within 4 weeks of first immunization or of a non-live vaccine within 2 weeks of first immunization
• Individuals who are breast-feeding, pregnant or planning to become pregnant during the study period
• Known allergy to atovaquone-proguanil (Malarone®), artemether-lumefantrine (Coartem), or any component of the investigational products
• History of anaphylaxis or other life-threatening reaction to a vaccine
• Participation in any study involving investigational vaccine or drug within 4 weeks prior to enrollment
• Evidence of increased cardiovascular disease risk; defined as \>10% five-year risk by non-laboratory method (Gaziano, 2008)
• Plan to participate in another investigational vaccine/drug research during the study
• Plan for major surgery between enrollment until 28 days post-CHMI
• Use or planned use of any drug with anti-malarial activity that would preceed or coincide with malaria challenge.
• Anticipated use of medications known to cause drug reactions with atovaquone-proguanil or artemether-lumefantrine such as cimetidine, metoclopramide, antacids, and kaolin

Sponsors & Collaborators

• Sanaria Inc.: lead
• Fred Hutchinson Cancer Center: collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: July 19, 2021
• Study Start: September 27, 2021
• Primary Completion: June 21, 2022
• Study Completion: June 21, 2022
• Last Updated: July 18, 2022

Record last verified: 2022-07

Locations

US (1)