Safety and Efficacy of Sanaria's PfSPZ-CVac in Malian Adults

NCT02996695 | Completed Phase 1 FDA Drug

• 2 other identifiers: 15-0052HHSN272201300022I
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Single site, double-blinded, randomized, placebo-controlled clinical trial of PfSPZ-CVac safety, tolerability, immunogenicity and efficacy against naturally occurring malaria in malaria-exposed Malian adults. The overall goal of the study is to evaluate if a regimen of PfSPZ-CVac (PfSPZ Challenge under chemoprophylaxis) is safe, well-tolerated, and provides sterile protection against naturally-occurring malaria in malaria-experienced adults. The study population includes 62 healthy, malaria-experienced adults aged 18-45 years, inclusive, residing in Bougoula Hameau and surrounding villages, Mali. The primary objective of this study is to assess the safety and tolerability of PfSPZ Challenge compared to placebo among malaria-experienced adults taking chloroquine prophylaxis (PfSPZ-CVac)

Conditions

Plasmodium Falciparum Infection

Keywords

Chloroquine Chemoprophylaxis; Efficacy; Immunogenicity; Malaria; Placebo; Plasmodium falciparum Sporozoites; Safety; Tolerability

Outcome Measures

Primary Outcomes (5)

• The number of serious adverse events (SAEs)

  45 days

• The number of solicited local and systemic adverse events (AE)

  Day 12 after vaccination

• The number of unsolicited AEs related to study product

  Day 12 after vaccination

• The severity of solicited local and systemic adverse events (AE)

  Day 12 after vaccination

• The severity of unsolicited AEs related to study product

  Day 12 after vaccination

Secondary Outcomes (6)

• Antibody titers against P. falciparum circumsporozoite protein (CSP) and other P. falciparum proteins at serology time points

  Days 3, 15, 31, 43,59, 71-77,87,245,and 413

• Markers of cell-mediated immunity as assessed by cells producing interferon gamma and/or IL-2

  Days 3, 15, 31, 43,59, 71-77,87,245,and 413

• Time to P. falciparum parasitemia, detected by qPCR

  within six months after the last vaccination

• Time to P. falciparum parasitemia, detected by qPCR

  within twelve months after the last vaccination

• Time to P. falciparum parasitemia, detected by thick blood film microscopy

  within twelve months after the last vaccination

Study Arms (2)

204,800 PfSPZ of PfSPZ Challenge

EXPERIMENTAL

204,800 PfSPZ of PfSPZ Challenge every 4 weeks x 3 doses by DVI, n=31

Drug: Artesunate; Drug: Chloroquine; Biological: PfSPZ (NF54) Challenge

NaCl placebo

PLACEBO COMPARATOR

NaCl placebo every 4 weeks x 3 doses by DVI, n=31

Drug: Artesunate; Drug: Chloroquine; Biological: PfSPZ (NF54) Challenge; Other: Placebo

Interventions

Artesunate DRUG

Artesunate is a succinic ester of artemether.

204,800 PfSPZ of PfSPZ Challenge; NaCl placebo

Chloroquine DRUG

4-aminoquinolone, antimalarial agent for oral administration

204,800 PfSPZ of PfSPZ Challenge; NaCl placebo

PfSPZ (NF54) Challenge BIOLOGICAL

Cryopreserved Plasmodium falciparum (Pf) fully infectious sporozoites (SPZ) that have been developed to be used to infect volunteers in controlled human malaria infection (CHMI) to assess the efficacy of antimalarial drugs and vaccines. The PfSPZ (NF54) Challenge contains a laboratory malaria strain isolated from a Dutch traveler to Africa.

204,800 PfSPZ of PfSPZ Challenge; NaCl placebo

Placebo OTHER

Placebo

NaCl placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A male or non-pregnant female aged 18-45 years inclusive at the time of screening.
• For women of childbearing potential, willingness not to become pregnant or breastfeed until one month after the last CQ dose\*.
• \*Pre-menopausal female participants will be referred to the local family planning clinic, which offers several means of contraception that are approved and recommended by the Mali Ministry of Health. Contraception (male or female condoms, diaphragm or cervical cap with spermicide, intrauterine device, or hormone-based contraceptive) should be started 30 days before the first vaccination and continue until 30 days after last vaccination.
• Written informed consent obtained from the participant before screening.
• Available and willing to participate in follow-up for the duration of study.
• Residing in Bougoula Hameau region and environs.
• In general good health based on clinical and laboratory investigation.

You may not qualify if:

• Previous vaccination with an investigational malaria vaccine.
• Use of an investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days before the first study vaccination, or planned use up to 30 days after last vaccination.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months before the first vaccination\*.
• \*This includes any dose level of oral steroids, but not inhaled steroids or topical steroids.
• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first study vaccination with the exception of tetanus toxoid.
• Confirmed or suspected immunosuppressive or immunodeficient condition.
• Confirmed or suspected autoimmune disease.
• History of allergic reactions or anaphylaxis to chloroquine, 4-aminoquinolone derivatives, artesunate and artemisinin derivatives, vaccinations or to any vaccine component.
• History of serious allergic reactions to any substance, requiring hospitalization or emergent medical care.
• History of allergy to any component of the PfSPZ Challenge product, including human serum albumin.
• Use or planned use of any drug with anti-malarial activity during the course of the study except for antimalarial medication administered by study clinicians.
• History of splenectomy.
• Confirmed pregnancy.
• Laboratory evidence of liver disease (ALT \> upper limit of normal).
• Laboratory evidence of renal disease (serum or plasma creatinine \> upper limit of normal).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Bamako - Epidemiology of Parasitic Diseases - Malaria Research and Training Center

Sikasso, Mali

Location

Related Publications (1)

• Coulibaly D, Kone AK, Traore K, Niangaly A, Kouriba B, Arama C, Zeguime A, Dolo A, Lyke KE, Plowe CV, Abebe Y, Potter GE, Kennedy JK, Galbiati SM, Nomicos E, Deye GA, Richie TL, James ER, Kc N, Sim BKL, Hoffman SL, Doumbo OK, Thera MA, Laurens MB; DMID 15-0052 PfSPZ-CVac Study Team. PfSPZ-CVac malaria vaccine demonstrates safety among malaria-experienced adults: A randomized, controlled phase 1 trial. EClinicalMedicine. 2022 Jul 30;52:101579. doi: 10.1016/j.eclinm.2022.101579. eCollection 2022 Oct.

  PMID: 35928033 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Artesunate; Chloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: December 19, 2016
• Study Start: April 6, 2017
• Primary Completion: June 22, 2018
• Study Completion: June 22, 2018
• Last Updated: December 2, 2019

Record last verified: 2017-07-19

Locations

MA (1)