A Phase 1 Trial of PfSPZ Vaccine in Healthy Adults to Determine Safety, Tolerability and Efficacy Against Heterologous CHMI

NCT05604521 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: USSPZV71U44AI167783-01
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

USSPZV7 is a randomized, phase 1, double-blind, placebo-controlled trial of Sanaria® 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) with the 7G8 clone of Plasmodium falciparum (Pf) conducted at 3 or 12 weeks after the third immunization. The trial is designed to determine if individuals living in a non-malaria endemic area such as the United States (US) are protected against heterologous CHMI conducted at these time points.

Conditions

Malaria; Malaria,Falciparum

Keywords

Malaria; Plasmodium falciparum; Sporozoites; PfSPZ Vaccine

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  The differences in proportions of vaccinees compared to controls experiencing related moderate, severe, or serious solicited and unsolicited adverse events and laboratory abnormalities after vaccination.

  Day of immunization to 28 days post immunization

Study Arms (4)

Group 1a: PfSPZ Vaccine

ACTIVE COMPARATOR

45 participants will receive 3 doses of 9.0x10\^5 PfSPZ Vaccine on Days 1, 8, and 29 with a total dose of 2.7x10\^6 PfSPZ Vaccine. Group 1a: Approximately half (22/23) of the volunteers will undergo CHMI 3 weeks after last immunization by exposure to 3.2x10\^3 PfSPZ Challenge (7G8).

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

Group 1b: PfSPZ Vaccine

ACTIVE COMPARATOR

45 participants will receive 3 doses of 9.0x10\^5 PfSPZ Vaccine on Days 1, 8, and 29 with a total dose of 2.7x10\^6 PfSPZ Vaccine. Group 1b: Approximately half (22/23) of the volunteers will undergo CHMI 12 weeks after last immunization by exposure to 3.2x10\^3 PfSPZ Challenge (7G8).

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

Group 2a: Normal Saline Controls

PLACEBO COMPARATOR

15 participants will receive 3 doses of normal saline on Days 1, 8, and 29. Group 2a: Approximately half (7/8) of the volunteers will undergo CHMI 3 weeks after last immunization by exposure to 3.2x10\^3 PfSPZ Challenge (7G8).

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

Group 2b: Normal Saline Controls

PLACEBO COMPARATOR

15 participants will receive 3 doses of normal saline on Days 1, 8, and 29. Group 2b: Approximately half (7/8) of the volunteers will undergo CHMI 12 weeks after last immunization by exposure to 3.2x10\^3 PfSPZ Challenge (7G8).

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

Interventions

PfSPZ Vaccine BIOLOGICAL

PfSPZ vaccine consists of radiation-attenuated, aseptic, purified Plasmodium falciparum (NF54) sporozoites (SPZ) cryopreserved in liquid nitrogen vapor phase (LNVP) at -150C to - 196C. PfSPZ Vaccine is composed of PfSPZ derived from the NF54 strain of Pf, which is thought to be from West Africa. PfSPZ Vaccine is diluted in phosphate buffered saline (PBS) with human serum albumin (HSA) to achieve the correct dosage and is administered by DVI.

Group 1a: PfSPZ Vaccine; Group 1b: PfSPZ Vaccine

PfSPZ Challenge (7G8) BIOLOGICAL

PfSPZ Challenge (7G8) is similar to PfSPZ Vaccine but has not been attenuated by radiation and is therefore infectious.PfSPZ Challenge (7G8) is composed of PfSPZ derived from the 7G8 clone of Pf, which is from Brazil.

Group 1a: PfSPZ Vaccine; Group 1b: PfSPZ Vaccine; Group 2a: Normal Saline Controls; Group 2b: Normal Saline Controls

Normal Saline OTHER

0.9% sodium chloride

Also known as: Placebo

Group 2a: Normal Saline Controls; Group 2b: Normal Saline Controls

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Healthy adults (male or non-pregnant female).
• 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 informed consent and satisfactorily complete a test of understanding with a passing score \>80%.
• Physical examination and laboratory results without clinically significant findings.
• Women 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. Women with a history of surgical or chemical sterilization (e.g. tubal ligation, hysterectomy, other).
• Willing to refrain from blood donation for 3 years following CHMI.
• Agree not to travel to a malaria endemic region during the trial.

You may not qualify if:

• Unable to provide informed consent including inability to pass the test of understanding, which is written in English for the US-based study sites.
• 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 3 or more non-live vaccines within 2 weeks of first immunization.
• Women 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.
• A history of malaria in the 2 years prior to screening.
• Participation in any study involving investigational vaccine or drug within 4 weeks prior to enrollment that in the estimation of the site PI might adversely affect the individual's safety or the quality of data to be collected.
• Evidence of increased cardiovascular disease risk; defined as \>10% five-year risk by nonlaboratory method.
• 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 precede or coincide with malaria challenge or vaccination.
• 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
• University of Maryland, Baltimore: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of Maryland, Baltimore, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201, United States

Location

Related Publications (3)

• Mordmuller B, Sulyok Z, Sulyok M, Molnar Z, Lalremruata A, Calle CL, Bayon PG, Esen M, Gmeiner M, Held J, Heimann HL, Woldearegai TG, Ibanez J, Flugge J, Fendel R, Kreidenweiss A, Kc N, Murshedkar T, Chakravarty S, Riyahi P, Billingsley PF, Church LWP, Richie TL, Sim BKL, Hoffman SL, Kremsner PG. A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection. NPJ Vaccines. 2022 Aug 23;7(1):100. doi: 10.1038/s41541-022-00510-z.

  PMID: 35999221 BACKGROUND

• Lyke KE, Singer A, Berry AA, Reyes S, Chakravarty S, James ER, Billingsley PF, Gunasekera A, Manoj A, Murshedkar T, Laurens MB, Church WP, Garver Baldwin LS, Sedegah M, Banania G, Ganeshan H, Guzman I, Reyes A, Wong M, Belmonte A, Ozemoya A, Belmonte M, Huang J, Villasante E, Sim BKL, Hoffman SL, Richie TL, Epstein JE; Warfighter II Study Team. Multidose Priming and Delayed Boosting Improve Plasmodium falciparum Sporozoite Vaccine Efficacy Against Heterologous P. falciparum Controlled Human Malaria Infection. Clin Infect Dis. 2021 Oct 5;73(7):e2424-e2435. doi: 10.1093/cid/ciaa1294.

  PMID: 32920641 BACKGROUND

• Berry AA, Richie TL, Church LWP, Laurens MB, Boyce C, Kc N, Joshi S, Koudjra AR, Butler L, Chen MC, Abebe Y, Murshedkar T, James ER, Billingsley PF, Sim BKL, Hoffman SL, Lyke KE. Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection. Malar J. 2025 Mar 17;24(1):88. doi: 10.1186/s12936-025-05299-5.

  PMID: 40098097 DERIVED

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

Limitations and Caveats

The trial was terminated early. The main reason for trial discontinuation was the inability to address the primary objectives of the study following an extended gap between the second and third doses. Thus, vaccination was not completed and efficacy measurement was not performed.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Sanaria Inc.

sanaria@sanaria.com

301-770-3222

Study Officials

• Kirsten E Lyke, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: October 28, 2022
• First Posted: November 3, 2022
• Study Start: December 6, 2022
• Primary Completion: September 5, 2023
• Study Completion: September 5, 2023
• Last Updated: November 25, 2024
• Results First Posted: November 25, 2024

Record last verified: 2024-11

Locations

US (1)