Safety and Efficacy of R0.6C Vaccine

NCT04862416 | Completed Phase 1 Results

• 2 other identifiers: STOP-TRANS2021-000017-17
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human phase I, open-label, single-site, dose escalation study to determine the safety, tolerability and Plasmodium falciparum transmission reducing activity of the R0.6C vaccine in two different adjuvant combinations.

Conditions

Malaria; Malaria,Falciparum

Keywords

Transmission; Transmission blocking vaccine; Malaria; Plasmodium falciparum; R0.6C; Vaccine

Outcome Measures

Primary Outcomes (2)

• Number of Serious Adverse Events and Grade 3 Adverse Events

  The number of serious adverse events and solicited and unsolicited grade 3 adverse events possibly, probably or definitely related to the vaccine in the period from first R0.6C administration up to 84 days after the last immunization.

  From first immunization up to 84 days after the last immunization

• Transmission Reducing Activity

  The functional transmission reducing activity in the standard membrane feeding assay of volunteer sera collected two weeks after the fourth R0.6C immunization (I4+14), compared to baseline (I1-1) within each of the four dose-adjuvant groups. The TRA was calculated by dividing the total number of oocysts in mosquitoes fed with I4+14 sera by total number of oocysts in mosquitoes fed with I1-1 sera.

  14 days after the fourth immunization

Secondary Outcomes (3)

• Number of Grade 1 and 2 Adverse Events

  From first immunization up to 84 days after the last immunization

• Transmission Reducing Activity

  14 days after immunization 1, 2 and 3. One day before immunization 4 and 84 days after immunization 4.

• Anti-6C Antibody Quantities

  14 days after each immunization. One day before immunization 4 and 84 days after immunization 4.

Study Arms (8)

1A 30μg R0.6C Alhydrogel

EXPERIMENTAL

3 subjects will receive four vaccinations of 30 ug R0.6C Alhydrogel on days 0, 28, 56 and 168.

Biological: R0.6C transmission blocking vaccine

1B 30μg R0.6C Alhydrogel + Matrix M1

EXPERIMENTAL

3 subjects will receive four vaccinations of 30 ug R0.6C Alhydrogel + Matrix M1 on days 0, 28, 56 and 168.

Biological: R0.6C transmission blocking vaccine

2A 30μg R0.6C Alhydrogel

EXPERIMENTAL

5 subjects will receive four vaccinations of 30 ug R0.6C Alhydrogel on days 0, 28, 56 and 168.

Biological: R0.6C transmission blocking vaccine

2B 30μg R0.6C Alhydrogel + Matrix M1

EXPERIMENTAL

5 subjects will receive four vaccinations of 30 ug R0.6C Alhydrogel + Matrix M1 on days 0, 28, 56 and 168.

Biological: R0.6C transmission blocking vaccine

3A 100μg R0.6C Alhydrogel

EXPERIMENTAL

3 subjects will receive four vaccinations of 100 ug R0.6C Alhydrogel on days 0, 28, 56 and 168.

Biological: R0.6C transmission blocking vaccine

3B 100μg R0.6C Alhydrogel + Matrix M1

EXPERIMENTAL

3 subjects will receive four vaccinations of 100 ug R0.6C Alhydrogel + Matrix M1 on days 0, 28, 56 and 168.

Biological: R0.6C transmission blocking vaccine

4A 100μg R0.6C Alhydrogel

EXPERIMENTAL

5 subjects will receive four vaccinations of 100 ug R0.6C Alhydrogel on days 0, 28, 56 and 168.

Biological: R0.6C transmission blocking vaccine

4B 100μg R0.6C Alhydrogel + Matrix M1

EXPERIMENTAL

5 subjects will receive four vaccinations of 100 ug R0.6C Alhydrogel + Matrix M1 on days 0, 28, 56 and 168.

Biological: R0.6C transmission blocking vaccine

Interventions

R0.6C transmission blocking vaccine BIOLOGICAL

Vaccination with R0.6C transmission blocking vaccine. Volunteers will sequentially receive four administrations of R0.6C intramuscularly in the deltoid muscle on alternating sides on days 0, 28, 56 and 168.

1A 30μg R0.6C Alhydrogel; 1B 30μg R0.6C Alhydrogel + Matrix M1; 2A 30μg R0.6C Alhydrogel; 2B 30μg R0.6C Alhydrogel + Matrix M1; 3A 100μg R0.6C Alhydrogel; 3B 100μg R0.6C Alhydrogel + Matrix M1; 4A 100μg R0.6C Alhydrogel; 4B 100μg R0.6C Alhydrogel + Matrix M1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must sign written informed consent to participate in the trial.
• Subject is a male or non-pregnant and non-lactating female age ≥ 18 and ≤ 55 years and in good health.
• Subject is able to understand planned study procedures and demonstrate comprehension of the protocol procedures and knowledge of study by passing a quiz (assessment of understanding).
• In the opinion of the investigator, the subject can and will comply with the requirements of the protocol.
• Subjects are available to attend all study visits and are reachable by phone throughout the entire study period from day -1 until day 224 (end of study).
• The subject will remain within reasonable travelling distance from the study center from day -1 until day 7 after each R0.6C administration and agrees not to travel to a malaria-endemic area during the study period
• Subject agrees to their general practitioner (GP) being informed about participation in the study and agrees to sign a form to request the release by their GP, and medical specialist when necessary, of any relevant medical information concerning possible contra-indications for participation in the study to the investigator(s).
• The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period according to current Sanquin guidelines.

You may not qualify if:

• Acute or chronic disease at time of R0.6C administration, clinically significant pulmonary, cardiovascular, hepatic, renal, neurological or immunological functional abnormality, as determined by medical history, physical examination or laboratory screening tests:
• Acute disease is defined as the presence of a moderate or severe illness with or without fever. For subjects with an illness on the day of R0.6C administration, the vaccination may be postponed up to 7 days.
• Fever is defined as an oral, axillary or tympanic temperature ≥ 38.0°C.
• Any abnormal and clinically significant baseline laboratory screening tests of ALT, AST, creatinine, hemoglobin, platelet count or total white blood cell count, as defined in the protocol according to the FDA Toxicity Grading Scale for Healthy Adult and Adolescent Subjects Enrolled in Preventative Vaccine Clinical Trials (appendix 1).
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
• Chronic use of i) immunosuppressive drugs, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.
• Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV).
• Use of any other investigational or non-registered product (drug or vaccine) during the study period.
• Known hypersensitivity to macrolides.
• Participation in any other clinical study involving an investigational product in the 30 days prior to the start of the study or during the study period.
• Receipt of any other vaccination within 30 days prior to the first R0.6C vaccination or planned vaccinations during the study period. Exceptions are made for vaccination against influenza and the novel coronavirus SARS-CoV2.
• Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study or CHMI.
• Body weight \> 115 kg
• Being an employee or student of the department of Medical Microbiology of the Radboudumc at the time of screening, or a person otherwise related to the investigator.
• Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Statens Serum Institut: collaborator
• Novavax: collaborator

Study Sites (1)

Radboud university medical center

Nijmegen, Gelderland, 6525GA, Netherlands

Location

Related Publications (1)

• Alkema M, Smit MJ, Marin-Mogollon C, Totte K, Teelen K, van Gemert GJ, van de Vegte-Bolmer M, Mordmuller BG, Reimer JM, Lovgren-Bengtsson KL, Sauerwein RW, Bousema T, Plieskatt J, Theisen M, Jore MM, McCall MBB. A Pfs48/45-based vaccine to block Plasmodium falciparum transmission: phase 1, open-label, clinical trial. BMC Med. 2024 Apr 23;22(1):170. doi: 10.1186/s12916-024-03379-y.

  PMID: 38649867 RESULT

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Matthew McCall
• Organization: Radboud university medical center

Matthew.McCall@radboudumc.nl

+31 24 361 43 56

Study Officials

• Matthew McCall, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: dr. MBB McCall

Model Details: Study groups will be assigned sequentially to low and high doses of R0.6C Vaccine. Within each dose group, participants will be assigned randomly (1:1) to one of two adjuvant arms (either Alhydrogel alone or Alhydrogel + Matrix-M).

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: April 28, 2021
• Study Start: May 17, 2021
• Primary Completion: June 29, 2022
• Study Completion: June 29, 2022
• Last Updated: March 5, 2025
• Results First Posted: March 5, 2025

Record last verified: 2025-02

Locations

NL (1)