Study Stopped
Subject withdrawals after temporal suspension of the trial (for personal, logistic reasons). At time of reinitiation the number of enrolled subjects did not meet the predefined threshold for continuation of the trial.
Safety and Efficacy of NF135 CPS Immunization
CPS135
Safety and Protective Efficacy of Chemoprophylaxis and Sporozoite Immunization With Plasmodium Falciparum NF135 Against Homologous and Heterologous Challenge Infection in Healthy Volunteers in the Netherlands
1 other identifier
interventional
43
1 country
1
Brief Summary
This is an open label, randomized, controlled clinical trial. The primary aim of this project is to determine the safety and tolerability of NF135.C10 sporozoite immunization under chemoprophylaxis against homologous and heterologous challenge infection.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Apr 2019
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 17, 2019
CompletedFirst Posted
Study publicly available on registry
January 23, 2019
CompletedStudy Start
First participant enrolled
April 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2021
CompletedResults Posted
Study results publicly available
May 11, 2022
CompletedMay 26, 2023
May 1, 2023
1.8 years
January 17, 2019
October 28, 2021
May 25, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Frequency of Adverse Events After NF135.C10 CPS Immunization
The number of adverse events will be recorded by the trial clinicians for all participants.
Cohort A: Inclusion until 35 days after challenge infection (35 weeks) Cohort B: Inclusion - premature end of study (22 weeks)
Magnitude of Adverse Events After NF135.C10 CPS Immunization
The severity of adverse events will be recorded (mild/moderate/severe) for each adverse event
Cohort A: Inclusion until 35 days after challenge infection (35 weeks) Cohort B: Inclusion - premature end of study (22 weeks)
Secondary Outcomes (1)
Time to Parasitemia
Day 1 - 28 after malaria challenge infection (28 days)
Study Arms (7)
1: NF135 CPS-immunization challenged by NF135
EXPERIMENTAL10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization.
2: Low dose NF135 CPS-immunization challenged by NF135
EXPERIMENTAL10 volunteers will receive three immunizations with 5 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization.
3: NF135 CPS-immunization (A/L) challenged by NF135
EXPERIMENTAL10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes.
4: NF135 CPS-immunization (A/L) challenged by NF54
EXPERIMENTAL10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. Volunteers will be challenged by the bites of 5 NF54 infected Anopheles mosquitoes 19 weeks after the last immunization.
5: Control group challenged by NF135.C10 Cohort A
OTHERChallenge infection control group: 3 volunteers will receive no immunization and will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization.
6: Control group challenged by NF54 Cohort B
OTHERChallenge infection control group: 3 volunteers will receive no immunization and will be challenged by the bites of 5 NF54 infected Anopheles mosquitoes 19 weeks after the last immunization.
7: Control group challenged by NF135 Cohort B
OTHERChallenge infection control group: 3 volunteers will receive no immunization and will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization.
Interventions
Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis.
Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites.
Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites.
Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization.
All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.
Eligibility Criteria
You may qualify if:
- Subject is aged ≥ 18 and ≤ 35 years and in good health.
- Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- Subject is able to communicate well with the investigator and is available to attend all study visits.
- The subject will remain within the Netherlands during the challenge period, not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.
- Subject agrees to inform his/her general practitioner about participation in the study and to sign a request to release by the General Practitioner (GP), and medical specialist when necessary, any relevant medical information concerning possible contra- indications for participation in the study.
- The subject agrees to refrain from blood donation throughout the study period and for a defined period thereafter according to current guidelines.
- For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study. Acceptable forms of contraception include: established use of oral, injected or implanted hormonal contraceptives; intrauterine device or intrauterine system; barrier methods (condoms or diaphragm with additional spermicide); male partner's sterilisation (with appropriate post-vasectomy documentation of absence of sperm in the ejaculate); true abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Subject agrees to refrain from intensive physical exercise (disproportionate to the subjects usual daily activity or exercise routine) during the malaria challenge period.
- Subject agrees to avoid additional triggers that may cause elevations in liver enzymes including alcohol from baseline up to 1 week post treatment.
- Subject has signed informed consent.
You may not qualify if:
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following.
- Body weight \<50 kg or Body Mass Index (BMI) \<18 or \>30 kg/m2 at screening. 1.2 A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiovascular events (including ischemia and myocarditis) in 1st or 2nd degree relatives \<50 years old.
- A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD deficiency.
- History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- Screening tests positive for Human Immunodeficiency Virus (HIV), or active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
- Chronic use of i) immunosuppressive drugs, ii) antibiotics or antimalarials, 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.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
- Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study.
- Known hypersensitivity to or contra-indications (including co-medication) for use of Mefloquine, Malarone or artemether-lumefantrine, or history of severe (allergic) reactions to mosquito bites.
- Receipt of any vaccinations in the 3 months prior to the start of the study or plans to receive any other vaccinations during the study period or up to 90 days thereafter.
- Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
- Being an employee or student of the department of Medical Microbiology of the Radboudumc or the department of Internal Medicine.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Radboud university medical centre
Nijmegen, Gelderland, 6525 GA, Netherlands
Related Publications (1)
van der Boor SC, Alkema M, van Gemert GJ, Teelen K, van de Vegte-Bolmer M, Walk J, van Crevel R, de Mast Q, Ockenhouse CF, Sauerwein RW, McCall MBB. Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial. BMC Med. 2023 Apr 7;21(1):137. doi: 10.1186/s12916-023-02788-9.
PMID: 37024868RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
\- Early termination of cohort B; heterologous protection could not be assessed.
Results Point of Contact
- Title
- Matthew McCall, MD, PhD
- Organization
- Radboud university medical center
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew BB McCall, MD PhD DTMH
Radboud University Medical Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- dr. MBB McCall
Study Record Dates
First Submitted
January 17, 2019
First Posted
January 23, 2019
Study Start
April 1, 2019
Primary Completion
February 1, 2021
Study Completion
February 1, 2021
Last Updated
May 26, 2023
Results First Posted
May 11, 2022
Record last verified: 2023-05