MalariaPhase 1NCT02858817
Safety and Protective Efficacy of IV Immunization With Cryopreserved PfSPZ Under A/P Chemoprophylaxis
A Phase 1 study testing atovaquone/proguanil 250mg/100mg (A/P), PfSPZ Challenge (NF54) and NaCl 0,9% in people with Malaria, run by University Hospital Tuebingen.
Trial summary
Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for repeat CHMI. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- atovaquone/proguanil 250mg/100mg (A/P), PfSPZ Challenge (NF54) and NaCl 0,9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 28 Nov 2016to 16 Nov 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults aged 18 to 45 years.
- Able and willing (in the Investigator's opinion) to comply with all study requirements.
- Willing to allow the investigators to discuss the volunteer's medical history with their general practitioner if required.
- Residence in Tübingen or surroundings for the period of the trial.
- Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year).
- Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria (currently four years in Germany).
Show all 12Show fewer
- Provision of written informed consent to receive PfSPZ Challenge for immunization and subsequently for CHMI.
- Reachable (24/7) by mobile phone during the immunization and CHMI period.
- Willingness to take A/P during immunization and a curative antimalarial regimen following CHMI.
- Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required.
- Answer all questions on the informed consent quiz correctly.
- A body mass index 18-35.
Who cannot join
- History of P.falciparum malaria.
- Planned travel to malaria endemic areas during the study period.
- Use of systemic antibiotics with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin,erythromycin, fluoroquinolones, or azithromycin).
- Receipt of an investigational product in the 90 days preceding enrollment, or planned receipt during the study period.
- HIV infection.
- Any confirmed or suspected immunosuppressive or immunodeficient state (e.g. repeated and/or unusual infections),history of infection caused by opportunistic organisms any infection or combination of infections that suggest underlying immunodeficiency, history of meningitis, encephalitis, septic shock, life-threatening soft tissue infection, more than one pneumonia, asplenia and/or chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)).
Show all 25Show fewer
- Use of immunoglobulins or blood products within 3 months prior to enrolment.
- Known (or signs consistent with) sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait, glucose-6-phosphate dehydrogenase deficiency.
- Pregnancy, lactation or intention to become pregnant during the study.
- Contraindications to the use of the following antimalarial medications: A/P, artemether-lumefantrine
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
- History of serious psychiatric condition that may affect participation in the study
- Any other serious chronic illness requiring hospital specialist supervision.
- Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 60 g (men) or 40 g (women) per day or a carbohydrate deficient transferrin (CDT) level ≥2.5%.
- Suspected or known injected drug abuse in the 5 years preceding enrollment.
- Positive for hepatitis B surface antigen (HBs-antigen).
- Seropositive for hepatitis C virus (antibodies to HCV).
- Falling in moderate risk or higher categories for fatal or non-fatal cardiovascular event within 5 years (>10%) determined by non-invasive criteria for cardiac risk 84.
- Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, clinically significant arrythmias, left bundle branch block, secondary or tertiary AV block
- A QT/QTcB interval >450 ms.
- Volunteers unable to be closely followed for social, geographic or psychological reasons.
- CrCL <30ml/min
- History of seizure (except uncomplicated febrile convulsion at childhood)
- Immunization with more than 3 other vaccines within the past month
- Any other significant disease, disorder, finding at medical history, biochemistry, hematology tests, urine analysis results or at clinical examination which, in the opinion of the investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
About this study
Official title: Safety and Protective Efficacy of Intravenous Immunization With Cryopreserved Plasmodium Falciparum Sporozoites Under Atovaquone/Proguanil Chemoprophylaxis
Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for repeat CHMI.
A total of 30 adult, healthy, malaria naïve volunteers will receive three injections by Direct Venous Inoculation (DVI) of either placebo (n = 10), 51,200 PfSPZ Challenge (NF54) (n = 10), or 150,000 PfSPZ Challenge (NF54) (n = 10) under chemoprophylaxis with A/P at 4 week intervals. The placebo will be normal saline (0.9% NaCl).
Read more
Ten weeks after the last dose of PfSPZ Challenge (NF54) for immunization, volunteers will undergo first CHMI and followed until asexual blood stage parasitemia, detected by quantitative real time PCR (qPCR) or thick blood smear microscopy. If parasitemic, they will be treated with A/P (used in this case as a standard treatment regimen). In the event of no parasitemia, volunteers will be followed until Day 28 post-CHMI and will not receive A/P.
Sixteen to forty-four weeks after the last immunization, a second CHMI will be administered to assess longevity and cross-strain protection. All volunteers will be followed up to 28 days post-inoculation. Those developing parasitemia will be treated with A/P.
Volunteers of Group A will have CHMI with PfSPZ Challenge (NF54) followed by PfSPZ Challenge (7G8). Volunteers of Group B will have CHMI with PfSPZ Challenge (NF54) or PfSPZ Challenge (7G8) followed by PfSPZ Challenge (7G8). In the case that protective efficacy in Group A is ≥75% CHMI sequence will be 7G8-7G8. In the case that protective efficacy against homologous Challenge in Group A is <75%, volunteers will receive the same sequence as in Group A (NF54-7G8).
- Conditions
- Malaria
- Being tested
- atovaquone/proguanil 250mg/100mg (A/P), PfSPZ Challenge (NF54), NaCl 0,9%
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atovaquone/proguanil 250mg/100mg (A/P)Drug
Also called Malarone
Combination drug for chemo-prophylaxis or treatment of malaria
PfSPZ Challenge (NF54)Biological
cryo-preserved Plasmodium falciparum sporozoites injected by venous inoculation
NaCl 0,9%Other
Also called Placebo
0.9% NaCl solution for injection
| Study group | Role | What they receive |
|---|---|---|
| 51,200 PfSPZ | Experimental | Three injections of 51,200 PfSPZ Challenge (P. falciparum strain: NF54) under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals Receives: Drug: atovaquone/proguanil 250mg/100mg (A/P); Biological: PfSPZ Challenge (NF54) |
| 150,000 PfSPZ | Experimental | Three injections of 150,000 PfSPZ Challenge (P. falciparum strain: NF54) under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals Receives: Drug: atovaquone/proguanil 250mg/100mg (A/P); Biological: PfSPZ Challenge (NF54) |
| Placebo | Placebo comparator | Three injections of NaCl 0,9% solution under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals Receives: Drug: atovaquone/proguanil 250mg/100mg (A/P); Other: NaCl 0,9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number or occurrence of related Grade 3 and 4 adverse events (AEs) and serious adverse events (SAEs)
Measured: from time of first administration of A/P until the last follow up visit, 414 days after first administration
Secondary outcomes (2)
Occurrence of any related AE
Measured: from time of first administration of A/P until the last follow up visit, 414 days after first administration
Proportion of protected volunteers
. Protection is defined as the absence of parasites in the peripheral blood for 28 days following first and second CHMI with PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) in volunteers receiving PfSPZ-CVac with A/P. Parasitemia is defined as at least one qPCR result above 100 parasites per mL among three positive results at least 12 hours apart or as a positive thick blood smear. Statistical testing is hierarchical: 1) protection against first CHMI, 2) protection against second CHMI.
Measured: From time of PfSPZ challenge administration until 28 days after PfSPZ challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2016 (estimated)
- Study start28 Nov 2016
- Primary completion16 Nov 2017
- Study completion16 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- Sanaria Inc.
- Responsible party
- Sponsor
- Investigators
- Peter G Kremsner, Prof, Principal investigator, University Hospital Tübingen, Tübingen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02858817
- Sponsor's protocol ID
- MALACHITE
- Status last verified
- Feb 2018
- First submitted
- 28 Jul 2016
- Last updated
- 15 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Protective Efficacy of Intravenous Immunization With Cryopreserved Plasmodium Falciparum Sporozoites Under Atovaquone/Proguanil Chemoprophylaxis
- ClinicalTrials.gov ID
- NCT02858817
- Acronym / sponsor ID
- MALACHITE
- Conditions
- Malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- Sanaria Inc.
- Study start
- 28 Nov 2016 (actual)
- Primary completion
- 16 Nov 2017 (actual)
- Study completion
- 16 Nov 2017 (actual)
- First posted
- 8 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for repeat CHMI.
A total of 30 adult, healthy, malaria naïve volunteers will receive three injections by Direct Venous Inoculation (DVI) of either placebo (n = 10), 51,200 PfSPZ Challenge (NF54) (n = 10), or 150,000 PfSPZ Challenge (NF54) (n = 10) under chemoprophylaxis with A/P at 4 week intervals. The placebo will be normal saline (0.9% NaCl).
Ten weeks after the last dose of PfSPZ Challenge (NF54) for immunization, volunteers will undergo first CHMI and followed until asexual blood stage parasitemia, detected by quantitative real time PCR (qPCR) or thick blood smear microscopy. If parasitemic, they will be treated with A/P (used in this case as a standard treatment regimen). In the event of no parasitemia, volunteers will be followed until Day 28 post-CHMI and will not receive A/P.
Sixteen to forty-four weeks after the last immunization, a second CHMI will be administered to assess longevity and cross-strain protection. All volunteers will be followed up to 28 days post-inoculation. Those developing parasitemia will be treated with A/P.
Volunteers of Group A will have CHMI with PfSPZ Challenge (NF54) followed by PfSPZ Challenge (7G8). Volunteers of Group B will have CHMI with PfSPZ Challenge (NF54) or PfSPZ Challenge (7G8) followed by PfSPZ Challenge (7G8). In the case that protective efficacy in Group A is ≥75% CHMI sequence will be 7G8-7G8. In the case that protective efficacy against homologous Challenge in Group A is <75%, volunteers will receive the same sequence as in Group A (NF54-7G8).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 51,200 PfSPZ | Experimental | Drug: atovaquone/proguanil 250mg/100mg (A/P), Biological: PfSPZ Challenge (NF54)Three injections of 51,200 PfSPZ Challenge (P. falciparum strain: NF54) under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals |
| 150,000 PfSPZ | Experimental | Drug: atovaquone/proguanil 250mg/100mg (A/P), Biological: PfSPZ Challenge (NF54)Three injections of 150,000 PfSPZ Challenge (P. falciparum strain: NF54) under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals |
| Placebo | Placebo comparator | Drug: atovaquone/proguanil 250mg/100mg (A/P), Other: NaCl 0,9%Three injections of NaCl 0,9% solution under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Healthy adults aged 18 to 45 years.
- Able and willing (in the Investigator's opinion) to comply with all study requirements.
- Willing to allow the investigators to discuss the volunteer's medical history with their general practitioner if required.
- Residence in Tübingen or surroundings for the period of the trial.
- Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year).
Key exclusion criteria (25 listed)
- History of P.falciparum malaria.
- Planned travel to malaria endemic areas during the study period.
- Use of systemic antibiotics with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin,erythromycin, fluoroquinolones, or azithromycin).
- Receipt of an investigational product in the 90 days preceding enrollment, or planned receipt during the study period.
- HIV infection.
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 |
|---|---|---|
| atovaquone/proguanil 250mg/100mg (A/P)Also: MalaroneCombination drug for chemo-prophylaxis or treatment of malaria | Drug | 150,000 PfSPZ, 51,200 PfSPZ, Placebo |
| PfSPZ Challenge (NF54)cryo-preserved Plasmodium falciparum sporozoites injected by venous inoculation | Biological | 150,000 PfSPZ, 51,200 PfSPZ |
| NaCl 0,9%Also: Placebo0.9% NaCl solution for injection | Other | Placebo |
Primary outcome
Number or occurrence of related Grade 3 and 4 adverse events (AEs) and serious adverse events (SAEs)
Time frame: from time of first administration of A/P until the last follow up visit, 414 days after first administration
2 secondary outcomes
Occurrence of any related AE
Time frame: from time of first administration of A/P until the last follow up visit, 414 days after first administration
Proportion of protected volunteers
Time frame: From time of PfSPZ challenge administration until 28 days after PfSPZ challenge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2019.
- Individual participant dataSharing planned: Undecided
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
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.
Peter G Kremsner, Prof principal investigator
University Hospital Tübingen, Tübingen, Germany
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing atovaquone/proguanil 250mg/100mg (A/P), PfSPZ Challenge (NF54) and NaCl 0,9% in people with Malaria, run by University Hospital Tuebingen.
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 12 inclusion and 25 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: finished, as of the sponsor's last update on 15 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number or occurrence of related Grade 3 and 4 adverse events (AEs) and serious adverse events (SAEs) (time frame: from time of first administration of A/P until the last follow up visit, 414 days after first administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jul 2019.