Age De-escalation Safety Trial of PfSPZ-LARC2 Vaccine in Burkina Faso

NCT06652737 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BFSPZL1
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-humans randomized, double-blind, placebo-controlled, age de-escalation Phase 1 trial of Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) malaria vaccine (Sanaria® PfSPZ-LARC2 Vaccine) administered to healthy, malaria-exposed adults and children by direct venous inoculation (DVI) to determine safety, tolerability, and immunogenicity. The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double gene deletion, of the Mei2 and LINUP genes. As a result, they undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream (no blood stage parasites are produced, either asexual or sexual). Because Pf parasites with the LARC phenotype replicate in the liver before disintegrating, they amplify and diversify parasite protein expression and are expected to be a potent immunogen to induce anti-malarial immunity, equaling or exceeding the potency and efficacy of the replication-competent chemo-attenuated Sanaria® PfSPZ-CVac (chloroquine). Because the parasites are intrinsically attenuated, they are also expected to be safe and well tolerated, similar to radiation-attenuated Sanaria® PfSPZ Vaccine and to the single-gene(Mei2)-deleted GA2 parasites (also LARC phenotype) tested at the Leiden University Medical Center (LUMC), which, like PfSPZ-LARC2 Vaccine, disintegrate after replicating in the liver. PfSPZ-LARC2 Vaccine thus avoids the safety concerns associated with PfSPZ-CVac, which uses fully infectious, non-attenuated parasites to achieve replication and depends on co-administered chloroquine for attenuation. In summary, the genetically attenuated PfSPZ-LARC2 Vaccine should combine the best-in-class immunogenic potency and protective efficacy of PfSPZ-CVac (chloroquine) with the excellent safety and tolerability of intrinsically attenuated PfSPZ Vaccine and GA2 vaccine. This trial is designed to test the hypotheses that:

1. 1.The vaccine is safe and well tolerated in each age group.
2. 2.The true rate of breakthrough blood stage infection (or other concerning adverse events) is less than about 5%, with an 95% confidence level (this will be the level of confidence that there are no breakthroughs if no breakthroughs occur in the 50 participants receiving PfSPZ-LARC2 Vaccine).

Conditions

Malaria Falciparum; Malaria Infection

Keywords

malaria; PfSPZ-LARC2 Vaccine; falciparum

Outcome Measures

Primary Outcomes (4)

• Assess safety, namely adequacy of attenuation, of PfSPZ-LARC2 Vaccine by measuring number of trial participants with presence of breakthrough blood stage infection

  Number of trial participants with presence of breakthrough blood stage infection during the first 28 days after immunization shown to be the vaccine strain. Participants will be followed for parasitemia by thick blood smear (TBS) after immunization. TBS to monitor for Pf blood stage infections will be performed every two days from Day 7 (day +6) to Day 19 (day +18) and then on Days 21, 24 and 29 (days +20, +23 and +28) .

  First 28 days after immunization with PfSPZ-LARC2 Vaccine

• Assess the safety of PfSPZ-LARC2 administration by measuring incidence of related grade 3 solicited and unsolicited adverse events (AEs) in the 28 days after PfSPZ-LARC2 Vaccine administration

  Participants will be followed for solicited and unsolicited adverse events 28 days after immunization. Incidence of possibly related, probably related or definitely related (a) grade 3 solicited adverse events (AEs) in the 28 days after PfSPZ-LARC2 Vaccine administration; and (b) grade 3 unsolicited AEs in the 28 days after PfSPZ-LARC2 Vaccine administration will be measured.

  First 28 days after immunization with PfSPZ-LARC2 Vaccine

• Assess the safety of PfSPZ-LARC2 administration by measuring incidence of related grade 3 abnormal laboratory values one week after PfSPZ-LARC2 Vaccine administration

  Incidence of possibly related, probably related or definitely related grade 3 abnormal laboratory values one week after PfSPZ-LARC2 Vaccine administration;

  7 days after immunization with PfSPZ-LARC2 Vaccine

• Assess the safety of PfSPZ-LARC2 administration by measuring incidence of related serious adverse events (SAEs) throughout the study period

  Incidence of possibly related, probably related or definitely related serious adverse events (SAEs) throughout the study period.

  Entire study period (approximately 6 months)

Secondary Outcomes (3)

• To further assess safety following vaccination by measuring incidence of mild to moderate solicited and unsolicited AEs in the 28 days after injection of PfSPZ-LARC2 Vaccine

  First 28 days following immunization with PfSPZ-LARC2 Vaccine

• To further assess safety following vaccination by measuring incidence of mild to moderate abnormal laboratory values one week after injection of PfSPZ-LARC2 Vaccine

  7 days after immunization with PfSPZ-LARC2 Vaccine

• To identify immune responses following vaccination and their association with age and sex by measuring Anti-P. falciparum circumsporozoite protein antibody levels two weeks after PfSPZ-LARC2 Vaccine administration.

  14 days after immunization with PfSPZ-LARC2 Vaccine

Study Arms (10)

Cohort 1: Group 1a Adult 2x10e5 PfSPZ-LARC2 Vaccine

EXPERIMENTAL

20-50-year-olds: 10 participants receive 3 injections of 2.0x10e5 PfSPZ-LARC2 Vaccine

Biological: PfSPZ-LARC2 Vaccine

Cohort 1: Group 1b Adult Normal Saline

PLACEBO COMPARATOR

20-50-year-olds: 5 participants receive 3 injections of normal saline

Biological: Normal Saline (Placebo)

Cohort 1: Group 2a Adult 4x10e5 PfSPZ-LARC2 Vaccine

EXPERIMENTAL

20-50-year-olds: 10 participants receive single injection of 4.0x10e5 PfSPZ-LARC2 Vaccine

Biological: PfSPZ-LARC2 Vaccine

Cohort 2: Group 3a 11-17year old 2x10e5 PfSPZ-LARC2 Vaccine

EXPERIMENTAL

11-17-year-olds: 10 participants receive single injection of 2.0x10e5 PfSPZ-LARC2 Vaccine

Biological: PfSPZ-LARC2 Vaccine

Cohort 2: Group 3b 11-17 year-olds Normal Saline

PLACEBO COMPARATOR

11-17-year-olds: 5 participants receive single injection of Normal Saline

Biological: Normal Saline (Placebo)

Cohort 2: Group 4a 6-10-year old 2x10e5 PfSPZ-LARC2 Vaccine

EXPERIMENTAL

6-10-year-olds: 10 participants receive single injection of 2.0x10e5 PfSPZ-LARC2 Vaccine

Biological: PfSPZ-LARC2 Vaccine

Cohort 2: Group 4b 6-10-year old Normal Saline

PLACEBO COMPARATOR

6-10-year-olds: 5 participants receive single injection of Normal Saline

Biological: Normal Saline (Placebo)

Cohort 3: Group 5a 1-5-year old 2x10e5 PfSPZ-LARC2 Vaccine

EXPERIMENTAL

1-5-year-olds: 10 participants receive one injection of 2.0x10e5 PfSPZ-LARC2 Vaccine

Biological: PfSPZ-LARC2 Vaccine

Cohort 3: Group 5b 1-5-year old Normal Saline

PLACEBO COMPARATOR

1-5-year-olds: 5 participants receive one injection of Normal Saline

Biological: Normal Saline (Placebo)

Cohort 1: Group 2b: Adults Normal Saline

PLACEBO COMPARATOR

20-50 year olds: 5 participants receive single injection of Normal Saline

Biological: Normal Saline (Placebo)

Interventions

PfSPZ-LARC2 Vaccine BIOLOGICAL

The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double genetic deletion, of the Mei2 and LINUP genes, and undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream (no blood stage parasites are produced)

Cohort 1: Group 1a Adult 2x10e5 PfSPZ-LARC2 Vaccine; Cohort 1: Group 2a Adult 4x10e5 PfSPZ-LARC2 Vaccine; Cohort 2: Group 3a 11-17year old 2x10e5 PfSPZ-LARC2 Vaccine; Cohort 2: Group 4a 6-10-year old 2x10e5 PfSPZ-LARC2 Vaccine; Cohort 3: Group 5a 1-5-year old 2x10e5 PfSPZ-LARC2 Vaccine

Normal Saline (Placebo) BIOLOGICAL

Normal Saline Placebo

Cohort 1: Group 1b Adult Normal Saline; Cohort 1: Group 2b: Adults Normal Saline; Cohort 2: Group 3b 11-17 year-olds Normal Saline; Cohort 2: Group 4b 6-10-year old Normal Saline; Cohort 3: Group 5b 1-5-year old Normal Saline

Eligibility Criteria

• Age: 1 Year - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy males and females, based on clinical and laboratory findings
• From the age 1 to 50 years
• Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or adolescents, and children with Z-score of the selected indicator (\[weight-for-height\], \[(height and BMI) for age\]) category within ±2SD.
• Residence in the study area for the duration of the study.
• Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study
• Willingness to be attended to by a study clinician and take all necessary medications prescribed during study period
• Agreement to provide contact information of a third party household member or close friend to study team
• Agreement not to participate in another clinical trial during the study period
• Agreement not to donate blood during the study period (until final clearance is completed)
• Able and willing to complete the study visit schedule over the study follow up period.
• Willingness to undergo HIV, hepatitis B (HBV), hepatitis C (HCV), and sickle cell anemia tests
• Volunteer participant (subjects 21 years of age and older) or the parent / guardian signing the informed consent (for subjects \<21 years of age) is able to demonstrate their understanding of the study by responding correctly to 9 out of 10 true/false statements (in a maximum of two attempts for those who failed to respond correctly to all true/false statements in the first attempt)
• Signed written informed consent, in accordance with local practice, provided by adult volunteers, parents or legal representatives and relevant assent for children participants as applicable
• Has not been treated with any antimalarial medication for at least two weeks prior to the initial clearance treatment.
• Female volunteers aged 12 years and above must be non-pregnant (as demonstrated by a negative urine pregnancy test), and provide consent / assent of their willingness to take protocol-defined measures not to become pregnant during the study and safety follow-up period. Acceptable measures to not become pregnant include 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) must provide written documentation of the procedure from a health care provider.

You may not qualify if:

• Unable to provide informed consent including inability to pass the test of understanding.
• 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 (AP), dihydroartemisinin-piperaquine (DHA-P), artemether-lumefantrine (AL), 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 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 non-laboratory method (Gaziano, 2008).
• Plan to participate in another investigational vaccine/drug research during the study.
• Plan for major surgery between enrollment until last study visit.
• Use or planned use of any drug with anti-malarial activity that would precede or coincide with vaccination through to 28 days after the last dose of vaccine.
• Anticipated use of medications known to cause drug interactions with DHAP (antiarrhythmics, neuroleptics, macrolide antibiotics, fluoroquinolones, imidazole and triazole antifungal agents, quinine, halofantrine, pentamidine and saquinavir, certain non-sedating antihistamines, all of which can affect QT intervals - see Section2.2.1.3) or AL (the same list of drugs affecting QT intervals plus rifampin, carbamazepine, phenytoin, St. John's wort and antiretroviral drugs).

Sponsors & Collaborators

• Sanaria Inc.: lead
• Groupe de Recherche Action en Sante: collaborator
• University of Maryland, Baltimore: collaborator
• Seattle Children's Hospital: collaborator

Study Sites (1)

Groupe de Recherche Action en Santé (GRAS) / Unité de Recherche Clinique de Sabou

Ouagadougou, 06, Burkina Faso

Location

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

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 Officials

• Thomas L Dr. Thomas L. Richie, MD PhD

  Sanaria Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: parasitology teams laboratory teams clinical teams
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The first study groups will assess 2 doses of vaccine, the target dose (2x10e5 PfSPZ) and a "maximize-the-chances-of-breakthrough" 2-fold higher dose (4x10e5 PfSPZ). These 2 doses will be assessed in adults (cohort 1). After SMC review of safety data from these two groups, the trial will proceed to older children (cohort 2) and then younger children (cohort 3). Each age strata will receive a single immunization, except for group 1 (adults), which will receive three immunizations on days 1, 29 and 57. The reason for a single immunization is that the chance of breakthrough will diminish after the first dose due to the induction of immunity - thus, repeat doses are not expected to contribute more information. However, with group 1, second and third immunizations will be administered to be sure that there is no increase in reactogenicity with repeated dosing and also to address the hypothetical concern that the attenuation of second and third doses is different from what we expect

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 22, 2024
• Study Start: March 4, 2025
• Primary Completion: February 18, 2026
• Study Completion: February 18, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-03

Locations

BU (1)