Dose-Escalating Study of Pfs230D1 in Combination With R21 in Matrix-M in African Adults

NCT06507605 | Completed Phase 1 DMC

• 1 other identifier: VIMT 001
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, individually randomized, double-blind, dose escalating study designed to evaluate the safety, tolerability, and immunogenicity of Pfs230D1 conjugate vaccines, R21 nanoparticle vaccine, or their combination conjugate vaccines, formulated on Matrix-M in healthy African adults aged 18 to 50 years.

Conditions

Prevention of Malaria Transmission and Clinical Malaria

Outcome Measures

Primary Outcomes (6)

• Number of Participants with Immediate adverse events

  Occurrence of immediate adverse events

  within 30-minutes following each dose

• Number of Participants with Solicited local adverse events

  Occurrence of solicited local adverse events

  for 7 days following each dose

• Number of Participants with Solicited systemic adverse events

  Occurrence of solicited systemic adverse events

  for 7 days following each dose

• Number of Participants with Unsolicited adverse events

  Occurrence of all unsolicited adverse events

  for 28 days following each dose

• Number of Participants with Abnormal Laboratory Values post-vaccination

  Any significant change from baseline for laboratory values defined as adverse events

  within 7 days following each dose

• Number of Participants with Serious adverse events

  Occurrence of serious adverse events

  Till 6 months post last dose

Secondary Outcomes (2)

• Anti-NANP IgG antibodies

  at 2 weeks post dose 3 in all treatment arms

• Anti-Pfs230D1 IgG antibodies

  at 2 weeks post dose 3 in all treatment arms

Study Arms (12)

Arm 1a (n=20)

EXPERIMENTAL

6μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M

Arm 1b (n=20)

EXPERIMENTAL

6μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M

Arm 1c (n=20)

EXPERIMENTAL

12μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M

Arm 1d (n=20)

EXPERIMENTAL

12μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M

Arm 1e (n=20)

ACTIVE COMPARATOR

5μg of R21 in 50μg Matrix-M

Biological: R21; Other: Matrix-M

Arm 1f (n=20)

ACTIVE COMPARATOR

10μg of R21 in 50μg Matrix-M

Biological: R21; Other: Matrix-M

Arm 2a (n=20)

EXPERIMENTAL

20μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M

Arm 2b (n=20)

EXPERIMENTAL

20μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M

Arm 2c (n=20)

EXPERIMENTAL

20μg Pfs230D1-CRM197 in 50μg Matrix-M

Biological: Pfs230D1-CRM197; Other: Matrix-M

Arm 2d (n=20)

EXPERIMENTAL

20μg Pfs230D1-EPA + 5μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-EPA; Other: Matrix-M

Arm 3a (n=20)

EXPERIMENTAL

40μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M

Arm 3b (n=20)

EXPERIMENTAL

40μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M

Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M

Interventions

R21 BIOLOGICAL

R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.

Arm 1a (n=20); Arm 1b (n=20); Arm 1c (n=20); Arm 1d (n=20); Arm 1e (n=20); Arm 1f (n=20); Arm 2a (n=20); Arm 2b (n=20); Arm 2d (n=20); Arm 3a (n=20); Arm 3b (n=20)

Pfs230D1-CRM197 BIOLOGICAL

Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.

Arm 1a (n=20); Arm 1b (n=20); Arm 1c (n=20); Arm 1d (n=20); Arm 2a (n=20); Arm 2b (n=20); Arm 2c (n=20); Arm 3a (n=20); Arm 3b (n=20)

Pfs230D1-EPA BIOLOGICAL

Recombinant Pfs230D1 conjugated to a recombinant Pseudomonas aeruginosa ExoProtein A (EPA)

Arm 2d (n=20)

Matrix-M OTHER

Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.

Arm 1a (n=20); Arm 1b (n=20); Arm 1c (n=20); Arm 1d (n=20); Arm 1e (n=20); Arm 1f (n=20); Arm 2a (n=20); Arm 2b (n=20); Arm 2c (n=20); Arm 2d (n=20); Arm 3a (n=20); Arm 3b (n=20)

Eligibility Criteria

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

You may qualify if:

• Age: 18 to 50 years old.
• Provides written informed consent.
• Able to understand and comply with planned study procedures and be available for the duration of the trial.
• In good general health and without clinically significant medical history in the opinion of the investigator.
• Females of childbearing potential must be willing to use reliable contraception from 21 days prior to Study Day 1 and until 1 month after the last vaccination.

You may not qualify if:

• Pregnant and breastfeeding females.
• Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels outside the local laboratory-defined reference ranges.
• Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of reference range.
• Infected with HIV, hepatitis B, hepatitis C.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies.
• Current or planned participation in an investigational product study until the time period of the last required study visit under this protocol.
• Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
• History of a severe allergic reaction or anaphylaxis.
• Known: Severe asthma, Autoimmune or antibody-mediated disease, Immunodeficiency, Seizure disorder, Asplenia or functional asplenia, Use of chronic oral or intravenous corticosteroids (excluding topical or nasal), Sickle cell disease.
• Any other condition that in the opinion of the investigator might jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or might render the subject unable to comply with the protocol.

Sponsors & Collaborators

• Serum Institute of India Pvt. Ltd.: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of Science, Technique and Technology of Bamako (Usttb)

Bamako, Mali

Location

MeSH Terms

Interventions

R21 monoclonal antibody; Matrix-M

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

Model Details: Participants will be randomized by cohorts as to one of the study arms to receive single antigen (Pfs230D1 or R21) or combination (Pfs230D1 + R21) with 50 μg of Matrix-M, all administered as an IM injection on a 1, 29, 57-day schedule.

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: July 18, 2024
• Study Start: August 30, 2024
• Primary Completion: January 24, 2026
• Study Completion: January 24, 2026
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)