Malaria,FalciparumCPS135NCT03813108
Safety and Efficacy of NF135 CPS Immunization
A study testing CPS-immunization, malaria challenge infection, P. falciparum NF135.C10 and malaria challenge infection, P. falciparum NF54 in people with Malaria,Falciparum and Controlled Human Malaria Infection, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria,Falciparum, Controlled Human Malaria Infection, Immunization; Infection
- What is being tested?
- CPS-immunization, malaria challenge infection, P. falciparum NF135.C10 and malaria challenge infection, P. falciparum NF54
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Apr 2019to 1 Feb 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
- 1.1 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.
- 1.3 A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD deficiency.
- 1.4 History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- 1.5 Screening tests positive for Human Immunodeficiency Virus (HIV), or active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
- 1.6 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.
Show all 15Show fewer
- 1.7 History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
- 1.8 Any history severe psychiatric disease diagnosed by a psychiatrist. 1.9 History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset, positive urine toxicology test for cocaine or amphetamines at screening or inclusion, or positive urine toxicology test for cannabis at inclusion.
- For female subjects: positive urine pregnancy test at screening or at inclusion.
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud university medical centre
Nijmegen, Gelderland, 6525 GA
About this study
Official title: 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
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.
Read the detailed description
A total of 49 healthy volunteers will be allocated to receive either three immunizations with 15 NF135.C10 infected Anopheles mosquitoes (n=30), 3 immunizations with 5 NF135.C10 infected mosquitoes (n=10) or no immunizations (n=6). Immunizations in cohort A (n=20) will be performed under mefloquine prophylaxis, spaced 4 weeks apart. In cohort B, volunteers will not take mefloquine prophylaxis, instead all volunteers will be treated presumptively on day 7 after each immunization with a curative regimen of artemether/lumefantrine, regardless of parasitaemia or symptoms.
Nineteen weeks after the last immunization, all volunteers plus naïve controls will be challenged either by the bites of 5 NF135.C10 (n=36) or 5 NF54 (n=13) infected mosquitoes. After challenge infection, volunteers will be followed up on an out-patient basis once daily for qPCR and safety lab measurements from day 6 until day 21 post challenge. All volunteers will be treated with a curative regimen of atovaquone/proguanil, either at the time of detection of blood stage parasitemia, or 28 days after challenge infection.
- Being tested
- CPS-immunization, malaria challenge infection, P. falciparum NF135.C10, malaria challenge infection, P. falciparum NF54, CPS-immunization (A/L), Atovaquone / Proguanil Oral Tablet [Malarone]
- Keywords
- Mosquito bites, Sporozoite, Immunization, Malaria, Falciparum
- Medical subject headings
- Malaria, Falciparum, Infections, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CPS-immunizationBiological
Also called Plasmodium falciparum NF135.C10 sporozoites, Mefloquine
Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis.
malaria challenge infection, P. falciparum NF135.C10Biological
Also called Plasmodium falciparum NF135.C10 sporozoites
Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites.
malaria challenge infection, P. falciparum NF54Biological
Also called Plasmodium falciparum NF54 sporozoites
Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites.
CPS-immunization (A/L)Biological
Also called Plasmodium falciparum NF135.C10 sporozoites, Artemether/lumefantrine (A/L)
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.
Atovaquone / Proguanil Oral Tablet [Malarone]Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1: NF135 CPS-immunization challenged by NF135 | Experimental | 10 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. Receives: Biological: CPS-immunization; Biological: malaria challenge infection, P. falciparum NF135.C10; Drug: Atovaquone / Proguanil Oral Tablet [Malarone] |
| 2: Low dose NF135 CPS-immunization challenged by NF135 | Experimental | 10 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. Receives: Biological: CPS-immunization; Biological: malaria challenge infection, P. falciparum NF135.C10; Drug: Atovaquone / Proguanil Oral Tablet [Malarone] |
| 3: NF135 CPS-immunization (A/L) challenged by NF135 | Experimental | 10 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. Receives: Biological: malaria challenge infection, P. falciparum NF135.C10; Biological: CPS-immunization (A/L); Drug: Atovaquone / Proguanil Oral Tablet [Malarone] |
| 4: NF135 CPS-immunization (A/L) challenged by NF54 | Experimental | 10 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. Receives: Biological: malaria challenge infection, P. falciparum NF54; Biological: CPS-immunization (A/L); Drug: Atovaquone / Proguanil Oral Tablet [Malarone] |
| 5: Control group challenged by NF135.C10 Cohort A | Other | Challenge 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. Receives: Biological: malaria challenge infection, P. falciparum NF135.C10; Drug: Atovaquone / Proguanil Oral Tablet [Malarone] |
| 6: Control group challenged by NF54 Cohort B | Other | Challenge 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. Receives: Biological: malaria challenge infection, P. falciparum NF54; Drug: Atovaquone / Proguanil Oral Tablet [Malarone] |
| 7: Control group challenged by NF135 Cohort B | Other | Challenge 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. Receives: Biological: malaria challenge infection, P. falciparum NF135.C10; Drug: Atovaquone / Proguanil Oral Tablet [Malarone] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Adverse Events After NF135.C10 CPS Immunization
The number of adverse events will be recorded by the trial clinicians for all participants.
Measured: 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
Measured: 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
The effectiveness of CPS-immunization with NF135 sporozoites to protect against malaria challenge infection with homologous N135.C10 or heterologous NF54 sporozoites will be determined by the time to parasitemia in immunized versus non-immunized volunteers after the challenge infection.
Measured: Day 1 - 28 after malaria challenge infection (28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2019
- Study start1 Apr 2019
- Primary completion1 Feb 2021
- Study completion1 Feb 2021
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malaria,FalciparumStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The PATH Malaria Vaccine Initiative (MVI)
- Responsible party
- Principal investigator, Matthew McCall, Radboud University Medical Center
- Investigators
- Matthew BB McCall, MD PhD DTMH, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03813108
- Sponsor's protocol ID
- CPS135
- Acronym
- CPS135
- Status last verified
- May 2023
- First submitted
- 17 Jan 2019
- Last updated
- 26 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 37024868
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03813108
- Acronym / sponsor ID
- CPS135 / CPS135
- Keywords
- Mosquito bites, Sporozoite, Immunization, Malaria, Falciparum
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- The PATH Malaria Vaccine Initiative (MVI)
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 1 Feb 2021 (actual)
- Study completion
- 1 Feb 2021 (actual)
- First posted
- 23 Jan 2019 (actual)
- Results
- Posted 11 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A total of 49 healthy volunteers will be allocated to receive either three immunizations with 15 NF135.C10 infected Anopheles mosquitoes (n=30), 3 immunizations with 5 NF135.C10 infected mosquitoes (n=10) or no immunizations (n=6). Immunizations in cohort A (n=20) will be performed under mefloquine prophylaxis, spaced 4 weeks apart. In cohort B, volunteers will not take mefloquine prophylaxis, instead all volunteers will be treated presumptively on day 7 after each immunization with a curative regimen of artemether/lumefantrine, regardless of parasitaemia or symptoms.
Nineteen weeks after the last immunization, all volunteers plus naïve controls will be challenged either by the bites of 5 NF135.C10 (n=36) or 5 NF54 (n=13) infected mosquitoes. After challenge infection, volunteers will be followed up on an out-patient basis once daily for qPCR and safety lab measurements from day 6 until day 21 post challenge. All volunteers will be treated with a curative regimen of atovaquone/proguanil, either at the time of detection of blood stage parasitemia, or 28 days after challenge infection.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 1: NF135 CPS-immunization challenged by NF135 | Experimental | Biological: CPS-immunization, Biological: malaria challenge infection, P. falciparum NF135.C10, Drug: Atovaquone / Proguanil Oral Tablet [Malarone]10 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 | Experimental | Biological: CPS-immunization, Biological: malaria challenge infection, P. falciparum NF135.C10, Drug: Atovaquone / Proguanil Oral Tablet [Malarone]10 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 | Experimental | Biological: malaria challenge infection, P. falciparum NF135.C10, Biological: CPS-immunization (A/L), Drug: Atovaquone / Proguanil Oral Tablet [Malarone]10 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 | Experimental | Biological: malaria challenge infection, P. falciparum NF54, Biological: CPS-immunization (A/L), Drug: Atovaquone / Proguanil Oral Tablet [Malarone]10 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 | Other | Biological: malaria challenge infection, P. falciparum NF135.C10, Drug: Atovaquone / Proguanil Oral Tablet [Malarone]Challenge 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 | Other | Biological: malaria challenge infection, P. falciparum NF54, Drug: Atovaquone / Proguanil Oral Tablet [Malarone]Challenge 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 | Other | Biological: malaria challenge infection, P. falciparum NF135.C10, Drug: Atovaquone / Proguanil Oral Tablet [Malarone]Challenge 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
- 1.1 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.
- 1.3 A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD deficiency.
- 1.4 History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- 1.5 Screening tests positive for Human Immunodeficiency Virus (HIV), or active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CPS-immunizationAlso: Plasmodium falciparum NF135.C10 sporozoites, MefloquineSubjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. | Biological | 1: NF135 CPS-immunization challenged by NF135, 2: Low dose NF135 CPS-immunization challenged by NF135 |
| malaria challenge infection, P. falciparum NF135.C10Also: Plasmodium falciparum NF135.C10 sporozoitesSubjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. | Biological | 1: NF135 CPS-immunization challenged by NF135, 2: Low dose NF135 CPS-immunization challenged by NF135, 3: NF135 CPS-immunization (A/L) challenged by NF135, 5: Control group challenged by NF135.C10 Cohort A, 7: Control group challenged by NF135 Cohort B |
| malaria challenge infection, P. falciparum NF54Also: Plasmodium falciparum NF54 sporozoitesSubjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites. | Biological | 4: NF135 CPS-immunization (A/L) challenged by NF54, 6: Control group challenged by NF54 Cohort B |
| CPS-immunization (A/L)Also: Plasmodium falciparum NF135.C10 sporozoites, Artemether/lumefantrine (A/L)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. | Biological | 3: NF135 CPS-immunization (A/L) challenged by NF135, 4: NF135 CPS-immunization (A/L) challenged by NF54 |
| Atovaquone / Proguanil Oral Tablet [Malarone]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. | Drug | 1: NF135 CPS-immunization challenged by NF135, 2: Low dose NF135 CPS-immunization challenged by NF135, 3: NF135 CPS-immunization (A/L) challenged by NF135, 4: NF135 CPS-immunization (A/L) challenged by NF54, 5: Control group challenged by NF135.C10 Cohort A, 6: Control group challenged by NF54 Cohort B, 7: Control group challenged by NF135 Cohort B |
Primary outcome
Frequency of Adverse Events After NF135.C10 CPS Immunization
Time frame: Cohort A: Inclusion until 35 days after challenge infection (35 weeks) Cohort B: Inclusion - premature end of study (22 weeks)
The number of adverse events will be recorded by the trial clinicians for all participants.
Magnitude of Adverse Events After NF135.C10 CPS Immunization
Time frame: Cohort A: Inclusion until 35 days after challenge infection (35 weeks) Cohort B: Inclusion - premature end of study (22 weeks)
The severity of adverse events will be recorded (mild/moderate/severe) for each adverse event
1 secondary outcome
Time to Parasitemia
Time frame: Day 1 - 28 after malaria challenge infection (28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37024868van 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.
Related trials for Malaria,Falciparum
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Not yet recruiting
Three-arm Cluster Randomised Control Trial Evaluation of Guardian Spatial Emanator as a Complimentary Vector Control Tool in Papua New Guinea
Malaria
Active, not recruitingPhase 4
Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics
Malaria,Falciparum, Malaria in Pregnancy
Not yet recruiting
Permethrin-Treated Baby Wraps for Malaria Prevention in Refugee Settings
Malaria (Plasmodium Falciparum), Malaria Incidence
RecruitingPhase 1/2
DON in Pediatric Cerebral Malaria
Malaria, Cerebral
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew BB McCall, MD PhD DTMH principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CPS-immunization, malaria challenge infection, P. falciparum NF135.C10 and malaria challenge infection, P. falciparum NF54 in people with Malaria,Falciparum and Controlled Human Malaria Infection, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Adverse Events After NF135.C10 CPS Immunization (time frame: Cohort A: Inclusion until 35 days after challenge infection (35 weeks) Cohort B: Inclusion - premature end of study (22 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03813108, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2023.