Pan-Malaria Transmission-Blocking Vaccine AnAPN1

NCT ID: NCT05905432

Last Updated: 2025-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-11
• Study Completion Date: 2025-01-31

Brief Summary

Malaria is still responsible for more than 627,000 deaths each year, predominantly among children under 5 years old. Current reductions in deaths have stagnated, and additional setbacks for malaria control programs due to the Coronavirus Disease 2019 (COVID-19) pandemic are expected. To achieve malaria elimination and eradication a leverage concerted approaches to reduce clinical disease and prevent new infections is a must. The existing malaria controls tools including the a recombinant protein-based malaria vaccine (RTS,S ,(trade name MosquirixMosquirix )), a malaria vaccine currently undergoing implementation studies and endorsed by the World Health Organization on October 7, 2021, can reduce disease burden for patients but cannot ultimately support malaria elimination and eradication since their effect on malaria transmission is at most partial. Consequently, complementary interventions, such as transmission-blocking vaccines (TBVs) may prove to be a cost-effective intervention that can reduce on-going residual transmission and the cascade of new infections.

Detailed Description

TBVs work by blocking parasite transmission to and from mosquitoes, with the added benefit of preventing the spread of parasites that have developed drug resistance or those that are vaccine-escape mutants of e.g. RTS,S. However, blocking transmission of all malaria species will be mandatory to achieve a globally relevant impact on malaria morbidity and mortality with Plasmodium falciparum and Plasmodium vivax being the most relevant targets. To date, the mosquito recombinant protein antigen vaccine Anopheline Alanyl Aminopeptidase N (AnAPN1)is the only TBV candidate that meets this need, wherein antibodies to this vaccine block both human malaria parasite species, underscoring its potential for supporting malaria elimination. The AnAPN1 vaccine consists of the AnAPN1 dimer antigen construct (UF6b) construct derived from the sequence of a protein of the mosquito midgut (Anopheles gambiae alanyl aminopeptidase), expressed as a recombinant protein in bacteria. With Global Health Innovative Technology Fund( GHIT) (G2020-208) support, the AnAPN1 reaches the First-In-Human milestone.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Dosage A1

n=2 will receive a dose of 20 mcg UF6b (A1), n=9 will receive 20 mcg AnAPN1: GLA-LSQ (5 mcg GLA/2 mcg LSQ) (A2)

Group Type: EXPERIMENTAL

Vaccine AnAPN1

Intervention Type: DRUG

AnAPN1 is a recombinant protein expressed in Escherichia coli. It consists of the UF6b construct, derived from the sequence of the Anopheles gambiae alanyl aminopeptidase N (XM\_318000.4) and will be formulated with or without Synthetic Glucopyranosyl Lipid A (GLA)- LSQ adjuvant. Route of administration is intramuscular.

Dosage B1

n=2 will receive 50 mcg UF6b (B1), n=9 will receive 50 mcg UF6b: GLA- LSQ (12.5 mcg GLA/5 mcg LSQ) (B2)

Group Type: EXPERIMENTAL

Vaccine AnAPN1

Intervention Type: DRUG

AnAPN1 is a recombinant protein expressed in Escherichia coli. It consists of the UF6b construct, derived from the sequence of the Anopheles gambiae alanyl aminopeptidase N (XM\_318000.4) and will be formulated with or without Synthetic Glucopyranosyl Lipid A (GLA)- LSQ adjuvant. Route of administration is intramuscular.

Dosage C1

n=2 will receive 100 mcg UF6b (C1); n=9 will receive 100 mcg UF6b: GLA- LSQ (25 mcg GLA/10 mcg LSQ) (C2)

Group Type: EXPERIMENTAL

Vaccine AnAPN1

Intervention Type: DRUG

AnAPN1 is a recombinant protein expressed in Escherichia coli. It consists of the UF6b construct, derived from the sequence of the Anopheles gambiae alanyl aminopeptidase N (XM\_318000.4) and will be formulated with or without Synthetic Glucopyranosyl Lipid A (GLA)- LSQ adjuvant. Route of administration is intramuscular.

Interventions

Vaccine AnAPN1

AnAPN1 is a recombinant protein expressed in Escherichia coli. It consists of the UF6b construct, derived from the sequence of the Anopheles gambiae alanyl aminopeptidase N (XM\_318000.4) and will be formulated with or without Synthetic Glucopyranosyl Lipid A (GLA)- LSQ adjuvant. Route of administration is intramuscular.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male and female volunteers aged 18-45 years.
• Able and willing (in the investigator's opinion) to comply with all trial requirements.
• General good health based on medical history and clinical examination.
• Written informed consent.
• Available to participate in follow up for the duration of trial (6 months following the last injection).
• Reachable by phone during the whole trial period.
• Women only: Must agree to practice continuous effective contraception for the duration of the trial.

Exclusion Criteria

• Positive for P. falciparum sexual and asexual stages by thick blood smear microscopy on admission and documented parasitologically confirmed malaria parasites of at least 1000 parasite/microliter in the past four weeks.
• Pregnancy, lactation, or intention to become pregnant during the trial.
• Previous participation in a malaria vaccine trial.
• HIV and microscopically detectable schistosomiasis and Soil-Transmitted helminth infection.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Global Health Innovative Technology Fund

OTHER

Sponsor Role: collaborator

Centre de Recherche Médicale de Lambaréné

OTHER

Sponsor Role: lead

Responsible Party

Prof. Ayola Akim ADEGNIKA

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ayôla Akim ADEGNIKA

Role: PRINCIPAL_INVESTIGATOR

Centre de Recherches Medicales de Lambarene

Rhoel DINGLASAN

Role: STUDY_DIRECTOR

University of Florida

Locations

Centre de Recherches Médicales de Lammbaréné

Lambaréné, Moyen-Ogooué Province, Gabon

Countries

Gabon

Other Identifiers

AnAPN1

Identifier Type: -

Identifier Source: org_study_id