MalariaPhase 1NCT03707041
Safety, Tolerability and Chemoprotective Activity of P218 in PfSPZ Challenge Model
A Phase 1 study testing P218 (1000 mg) Oral Capsules, P218 (100 mg) Oral Capsules and PfSPZ Challenge in people with Malaria, run by Medicines for Malaria Venture at 1 site in Belgium.
Trial summary
This was a single centre, randomised, double-blind, placebo-controlled Phase Ib study, to evaluate the safety, tolerability and chemoprotective activity of P218 in a controlled P. falciparum sporozoite infection model. 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?
- P218 (1000 mg) Oral Capsules, P218 (100 mg) Oral Capsules and PfSPZ Challenge
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteBelgium
- Study dates
- 16 Nov 2018to 3 Jun 2019
- Phase
- Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
None listed.
Who cannot join
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency (due to possible hemolysis induced by primaquine treatment at study end in G6PD deficient subjects).
- Personal history of malaria.
- Volunteer has travelled to or lived in a malaria-endemic area for more than 4 weeks during the 12 months prior to first IMP administration, or spent any time in an endemic area during the 4 weeks prior to first IMP administration.
- Plans to travel to malaria-endemic region during the study period up to last follow-up visit.
- Previous participation in any malaria vaccine or CHMI study.
- Falling in moderate or higher risk category for a fatal or non-fatal cardiovascular event within 10 years (≥5%) determined by a validated risk estimation system e.g. SCORE [13].
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- Use of medications known to interact with atovaquone-proguanil (Malarone®), artemether-lumefantrine (Riamet®) or primaquine (Primaquine®) such as cimetidine, metoclopramide or antacids, or an anticipated requirement for the use of these at any point during the study period (see Section 6.2).
- Use of systemic antibiotics with known antimalarial activity within 30 days (or 5 half-lives whichever is longer) of first IMP administration (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones or azithromycin) or an anticipated requirement for the use of these during the study period (see Section 6.2).
- Receipt of blood or blood-derived products (including immunoglobulin) within 3 months prior to screening. Receipt of packed red blood cells given for an emergent indication in an otherwise healthy person, and not required as ongoing treatment is not exclusionary (for example packed red blood cells emergently given during an elective surgery).
- Note: In case of an out-of-range clinical laboratory test, vital sign or ECG value that will determine a subject's eligibility, or in case of a positive drug screen, a retest or expert evaluation can be requested. Results of any retest must be available prior to inoculation. The result of the retest will be considered for subject eligibility at the investigator's discretion. Subjects can be rescreened at the discretion of the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Centre, Randomised, Double-blind, Placebo-controlled, Phase Ib Study to Evaluate the Safety, Tolerability and Chemoprotective Antimalarial Activity of P218 Against Controlled Human Malaria Infection With Plasmodium Falciparum Sporozoite Challenge in Non-immune Healthy Adult Volunteers
This was a single centre, randomised, double-blind, placebo-controlled Phase Ib study, to evaluate the safety, tolerability and chemoprotective activity of P218 in a controlled P. falciparum sporozoite infection model.
Healthy men and women, aged 18 to 45 years were to be enrolled in 3 study cohorts and to be administered either P218 or placebo twice, 48 hours apart. Subjects in cohorts 2 and 3 were to be inoculated with P. falciparum sporozoites. Enrolment in cohorts was to proceed sequentially, to facilitate review of data by a Safety Review Team (SRT) before proceeding with a subsequent cohort.
In cohort 1, safety and tolerability of P218 was assessed. In cohorts 2 and 3, chemoprotective activity of P218 against malaria infection was assessed, as well as the Influence of time of initiation of the P218 treatment on the protective effect.
Read the detailed description
This was a single centre, randomised, double-blind, placebo-controlled Phase Ib study, to evaluate the safety, tolerability and chemoprotective activity of P218 in a controlled P. falciparum sporozoite infection model.
32 healthy men and women, aged 18 to 45 years were to be enrolled in 3 cohorts of respectively 8, 12 and 12 subjects. A subject could be enrolled in one cohort only and was to be randomised in a 3:1 ratio, to receive two consecutive administrations, 48 hours apart, of either P218 or placebo. Enrolment in cohorts proceeded sequentially, to facilitate review of data by a Safety Review Team (SRT) before populating a subsequent cohort.
Cohort 1 consisted of 2 subgroups of subjects, to be enrolled sequentially: subgroup 1 was to be composed of 2 subjects: one to receive two 1000 mg doses of P218 and one to receive placebo twice. Subgroup 2 was to be composed of 6 subjects: five to receive two 1000 mg doses of P218 and one to receive placebo twice. Subjects in subgroup 2 would not be treated until 24 hours after second IMP administration in the last subject of subgroup 1 and only after review of the safety data from subgroup 1 by the PI. Duration of each subject treatment and follow-up in Cohort 1 was 9 days. Progression to Cohort 2 was subject to review of the safety and tolerability data by a SRT.
Cohort 2 consisted of three subgroups of subjects, to be enrolled sequentially. Subgroup 1 was to be composed of 2 subjects: one to receive two 1000 mg doses of P218 and one to receive placebo twice. Subgroups 2 and 3 were to be composed of 5 subjects each: four to receive two 1000 mg doses of P218 and one to receive placebo twice. Subjects in subgroup 2 would not be treated until 24 hours after second IMP administration in the last subject of subgroup 1. On Day 1, each subject in Cohort 2 would be administered 3200 P. falciparum sporozoites (PfSPZ Challenge) by direct venous inoculation (DVI). First administration of 1000 mg of P218 or placebo will take place 2 hours after PfSPZ Challenge DVI; second administration of 1000 mg of P218 or placebo would take place 48 hours later. As of Day 7, parasitemia in every subject was to be assessed daily until the installation of malarial infection or until Day 28. Overall duration of each subject observation in Cohort 2 was 35 days. Progression to Cohort 3 was subject to assessment of safety and parasitemia data, as well as malaria signs and symptoms by a SRT.
Cohort 3 was to consist of two subgroups each with 6 subjects, to be enrolled sequentially. Treatment was to be allocated in a ratio of 3 active: 1 placebo. In each subgroup, at least 1 subject was to receive placebo and the remaining subjects would receive two 100 mg doses of P218 48 hours apart. Subjects in subgroup 2 would not be inoculated until 24 hours after second IMP administration in the last subject of subgroup 1. On Day 1, subjects were to be administered 3200 P. falciparum sporozoites by DVI. As of Day 7, parasitemia in every subject was to be assessed daily until the installation of malarial infection or until Day 28. Overall duration of each subject observation in Cohort 3 is 35 days.
All subjects in Cohorts 2 and 3 would receive antimalarial rescue therapy, either upon installation of malarial infection or on Day 28 or if leaving the study prematurely.
In Cohort 1, safety and tolerability of two 1000 mg doses of P218 administered 48 hours apart was to be assessed over 9 days of observation. Pharmacokinetic assessments of P218 and its main metabolites were to take place over 9 days of observation.
In Cohorts 2 and 3, chemoprotective activity of two doses P218 (1000 mg or 100 mg respectively) administered 48 hours apart, were to be assessed over 28 days. Safety and tolerability of two doses of P218 (1000 mg or 100 mg respectively) administered 48 hours apart were to be assessed over 35 days of observation. Pharmacokinetic assessments of P218 would take place over 9 days of observation.
- Conditions
- Malaria
- Being tested
- P218 (1000 mg) Oral Capsules, Placebo Oral Capsules, P218 (100 mg) Oral Capsules, PfSPZ Challenge
- Keywords
- malaria, PfSPZ Challenge, chemoprotection
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P218 (1000 mg) Oral CapsulesDrug
1000 mg P218 (4 x 250 mg capsules)
Placebo Oral CapsulesDrug
Placebo capsules matched to the P218 capsules with regard to appearance and taste
P218 (100 mg) Oral CapsulesDrug
100 mg P218 (2 x 50 mg capsules)
PfSPZ ChallengeBiological
3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
| Study group | Role | What they receive |
|---|---|---|
| P218 1000 mg (Oral Capsules) - Cohort 1 | Experimental | Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart Receives: Drug: P218 (1000 mg) Oral Capsules |
| P218 Placebo Oral Capsules - Cohort 1 | Placebo comparator | Two administrations of P218 placebo (capsules p.o.), 48 hours apart Receives: Drug: Placebo Oral Capsules |
| P218 1000 mg (Oral Capsules) - Cohort 2 | Experimental | One administration of 1000 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 1000 mg P218 (capsules p.o.), 48 hours after first administration. Receives: Drug: P218 (1000 mg) Oral Capsules; Biological: PfSPZ Challenge |
| P218 Placebo Oral Capsules - Cohort 2 | Placebo comparator | One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.,) 48 hours after first administration. Receives: Drug: Placebo Oral Capsules; Biological: PfSPZ Challenge |
| P218 100 mg (Oral Capsules) - Cohort 3 | Experimental | One administration of 100 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 100 mg P218 (capsules p.o.), 48 hours after first administration. Receives: Drug: P218 (100 mg) Oral Capsules; Biological: PfSPZ Challenge |
| P218 Placebo Oral Capsule - Cohort 3 | Active comparator | One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration. Receives: Drug: Placebo Oral Capsules; Biological: PfSPZ Challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohort 1: Number of TEAEs
Incidence, severity and relationship to the treatment of observed or self-reported treatment emergent adverse events (TEAEs) after two single doses of 1000 mg P218 administered 48 hours apart in healthy adult volunteers.
Measured: 9 days
Cohorts 2 and 3: Geometric Mean Time From PfSPZ Challenge to First Quantitative Polymerase Chain Reaction (qPCR) Outcome Equal or Greater Than 250 Asexual Parasites Per mL of Blood
Chemoprotective activity of two single doses of 1000 mg P218 administered 2 hours after PfSPZ Challenge and 48 hours later in healthy adult volunteers
Measured: Number of days from PfSPZ Challenge DVI to positive parasitaemia, or 28 days
Secondary outcomes (7)
Cohorts 2 and 3: Number of P218 TEAEs
Incidence, severity and relationship to the P218 treatment of observed or self-reported treatment emergent adverse events in non-immune healthy adult volunteers after two single doses of 1000 mg P218 administered 48 hours apart in a controlled human malaria infection (PfSPZ Challenge)
Measured: 35 days
Cohorts 2 and 3: Number of PfSPZ Challenge TEAEs
Incidence, severity and relationship to the PfSPZ Challenge of observed or self-reported treatment emergent adverse events in non-immune healthy adult volunteers before and after P218 administration
Measured: 35 days
Cohorts 2 and 3: Malaria Clinical Score at the Time of Introduction of Rescue Therapy
The malaria clinical score consists of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension.
To determine severity of the 14 signs/symptoms the CTCAE grading scale grade 1 - 5 was used. Mild (1) equates to CTCAE grade 1, Moderate (2) equates to CTCAE grade 2 and Severe (3) equates to CTCAE grade 3 or above. Individual scores for each symptom as well as the total score were recorded.
Measured: On the day of positive parasitaemia or on Day 28
Cohorts 1, 2 and 3: P218 AUC[0-48h] - Day 1
Area under the P218 plasma concentration-time curve from first administration to 48 hours after first administration
Measured: 9 days
Cohort 1: P218-beta-acyl-glucuronide-OH AUC[48-96h]
Area under the P218-beta-acyl-glucuronide-OH plasma concentration-time curve from 48 hours after first P218 administration to 96 hours after first P218 administration
Measured: 9 days
Cohorts 1, 2 and 3: P218 Cmax - Day 1
Maximum observed P218 plasma concentration after each P218 administration
Measured: 9 days
Cohorts 1, 2 and 3: P218 Tmax - Day 1
Time to P218 Cmax after each P218 administration
Measured: 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start16 Nov 2018
- Primary completion27 May 2019
- Study completion3 Jun 2019
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.
- Other trials for MalariaStudies of the same condition, open and under way.
- 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
- Parallel groups
- Model description
- In each of the three treatment cohorts, subjects will be randomly allocated to receive either P218 or placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- SGS Life Sciences, a division of SGS Belgium NV, Institute of Tropical Medicine, Belgium, Washington University School of Medicine, Swiss BioQuant, PrimeVigilance Ltd., UK, Biologic LLP, UK, Sanaria Inc., FGK Representative Service B.V., The Netherlands
- Responsible party
- Sponsor
- Investigators
- Cristina Donini, PhD, Study director, MMVPieter-Jan Berghmans, MD, Principal investigator, SGS Belgium NV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03707041
- Sponsor's protocol ID
- MMV_P218_17_01
- Other IDs
- 2018-003004-39, 2018
- Status last verified
- Mar 2021
- First submitted
- 9 Oct 2018
- Last updated
- 9 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Centre, Randomised, Double-blind, Placebo-controlled, Phase Ib Study to Evaluate the Safety, Tolerability and Chemoprotective Antimalarial Activity of P218 Against Controlled Human Malaria Infection With Plasmodium Falciparum Sporozoite Challenge in Non-immune Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT03707041
- Acronym / sponsor ID
- MMV_P218_17_01
- Conditions
- Malaria
- Keywords
- malaria, PfSPZ Challenge, chemoprotection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- SGS Life Sciences, a division of SGS Belgium NV, Institute of Tropical Medicine, Belgium, Washington University School of Medicine, Swiss BioQuant, PrimeVigilance Ltd., UK, Biologic LLP, UK, Sanaria Inc., FGK Representative Service B.V., The Netherlands
- Study start
- 16 Nov 2018 (actual)
- Primary completion
- 27 May 2019 (actual)
- Study completion
- 3 Jun 2019 (actual)
- First posted
- 16 Oct 2018 (actual)
- Results
- Posted 9 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a single centre, randomised, double-blind, placebo-controlled Phase Ib study, to evaluate the safety, tolerability and chemoprotective activity of P218 in a controlled P. falciparum sporozoite infection model.
Healthy men and women, aged 18 to 45 years were to be enrolled in 3 study cohorts and to be administered either P218 or placebo twice, 48 hours apart. Subjects in cohorts 2 and 3 were to be inoculated with P. falciparum sporozoites. Enrolment in cohorts was to proceed sequentially, to facilitate review of data by a Safety Review Team (SRT) before proceeding with a subsequent cohort.
In cohort 1, safety and tolerability of P218 was assessed. In cohorts 2 and 3, chemoprotective activity of P218 against malaria infection was assessed, as well as the Influence of time of initiation of the P218 treatment on the protective effect.
Detailed description
This was a single centre, randomised, double-blind, placebo-controlled Phase Ib study, to evaluate the safety, tolerability and chemoprotective activity of P218 in a controlled P. falciparum sporozoite infection model.
32 healthy men and women, aged 18 to 45 years were to be enrolled in 3 cohorts of respectively 8, 12 and 12 subjects. A subject could be enrolled in one cohort only and was to be randomised in a 3:1 ratio, to receive two consecutive administrations, 48 hours apart, of either P218 or placebo. Enrolment in cohorts proceeded sequentially, to facilitate review of data by a Safety Review Team (SRT) before populating a subsequent cohort.
Cohort 1 consisted of 2 subgroups of subjects, to be enrolled sequentially: subgroup 1 was to be composed of 2 subjects: one to receive two 1000 mg doses of P218 and one to receive placebo twice. Subgroup 2 was to be composed of 6 subjects: five to receive two 1000 mg doses of P218 and one to receive placebo twice. Subjects in subgroup 2 would not be treated until 24 hours after second IMP administration in the last subject of subgroup 1 and only after review of the safety data from subgroup 1 by the PI. Duration of each subject treatment and follow-up in Cohort 1 was 9 days. Progression to Cohort 2 was subject to review of the safety and tolerability data by a SRT.
Cohort 2 consisted of three subgroups of subjects, to be enrolled sequentially. Subgroup 1 was to be composed of 2 subjects: one to receive two 1000 mg doses of P218 and one to receive placebo twice. Subgroups 2 and 3 were to be composed of 5 subjects each: four to receive two 1000 mg doses of P218 and one to receive placebo twice. Subjects in subgroup 2 would not be treated until 24 hours after second IMP administration in the last subject of subgroup 1. On Day 1, each subject in Cohort 2 would be administered 3200 P. falciparum sporozoites (PfSPZ Challenge) by direct venous inoculation (DVI). First administration of 1000 mg of P218 or placebo will take place 2 hours after PfSPZ Challenge DVI; second administration of 1000 mg of P218 or placebo would take place 48 hours later. As of Day 7, parasitemia in every subject was to be assessed daily until the installation of malarial infection or until Day 28. Overall duration of each subject observation in Cohort 2 was 35 days. Progression to Cohort 3 was subject to assessment of safety and parasitemia data, as well as malaria signs and symptoms by a SRT.
Cohort 3 was to consist of two subgroups each with 6 subjects, to be enrolled sequentially. Treatment was to be allocated in a ratio of 3 active: 1 placebo. In each subgroup, at least 1 subject was to receive placebo and the remaining subjects would receive two 100 mg doses of P218 48 hours apart. Subjects in subgroup 2 would not be inoculated until 24 hours after second IMP administration in the last subject of subgroup 1. On Day 1, subjects were to be administered 3200 P. falciparum sporozoites by DVI. As of Day 7, parasitemia in every subject was to be assessed daily until the installation of malarial infection or until Day 28. Overall duration of each subject observation in Cohort 3 is 35 days.
All subjects in Cohorts 2 and 3 would receive antimalarial rescue therapy, either upon installation of malarial infection or on Day 28 or if leaving the study prematurely.
In Cohort 1, safety and tolerability of two 1000 mg doses of P218 administered 48 hours apart was to be assessed over 9 days of observation. Pharmacokinetic assessments of P218 and its main metabolites were to take place over 9 days of observation.
In Cohorts 2 and 3, chemoprotective activity of two doses P218 (1000 mg or 100 mg respectively) administered 48 hours apart, were to be assessed over 28 days. Safety and tolerability of two doses of P218 (1000 mg or 100 mg respectively) administered 48 hours apart were to be assessed over 35 days of observation. Pharmacokinetic assessments of P218 would take place over 9 days of observation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- In each of the three treatment cohorts, subjects will be randomly allocated to receive either P218 or placebo.
| Arm | Type | Receives |
|---|---|---|
| P218 1000 mg (Oral Capsules) - Cohort 1 | Experimental | Drug: P218 (1000 mg) Oral CapsulesTwo administrations of 1000 mg P218 (capsules p.o.), 48 hours apart |
| P218 Placebo Oral Capsules - Cohort 1 | Placebo comparator | Drug: Placebo Oral CapsulesTwo administrations of P218 placebo (capsules p.o.), 48 hours apart |
| P218 1000 mg (Oral Capsules) - Cohort 2 | Experimental | Drug: P218 (1000 mg) Oral Capsules, Biological: PfSPZ ChallengeOne administration of 1000 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 1000 mg P218 (capsules p.o.), 48 hours after first administration. |
| P218 Placebo Oral Capsules - Cohort 2 | Placebo comparator | Drug: Placebo Oral Capsules, Biological: PfSPZ ChallengeOne administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.,) 48 hours after first administration. |
| P218 100 mg (Oral Capsules) - Cohort 3 | Experimental | Drug: P218 (100 mg) Oral Capsules, Biological: PfSPZ ChallengeOne administration of 100 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 100 mg P218 (capsules p.o.), 48 hours after first administration. |
| P218 Placebo Oral Capsule - Cohort 3 | Active comparator | Drug: Placebo Oral Capsules, Biological: PfSPZ ChallengeOne administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (10 listed)
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency (due to possible hemolysis induced by primaquine treatment at study end in G6PD deficient subjects).
- Personal history of malaria.
- Volunteer has travelled to or lived in a malaria-endemic area for more than 4 weeks during the 12 months prior to first IMP administration, or spent any time in an endemic area during the 4 weeks prior to first IMP administration.
- Plans to travel to malaria-endemic region during the study period up to last follow-up visit.
- Previous participation in any malaria vaccine or CHMI study.
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 |
|---|---|---|
| P218 (1000 mg) Oral Capsules1000 mg P218 (4 x 250 mg capsules) | Drug | P218 1000 mg (Oral Capsules) - Cohort 1, P218 1000 mg (Oral Capsules) - Cohort 2 |
| Placebo Oral CapsulesPlacebo capsules matched to the P218 capsules with regard to appearance and taste | Drug | P218 Placebo Oral Capsule - Cohort 3, P218 Placebo Oral Capsules - Cohort 1, P218 Placebo Oral Capsules - Cohort 2 |
| P218 (100 mg) Oral Capsules100 mg P218 (2 x 50 mg capsules) | Drug | P218 100 mg (Oral Capsules) - Cohort 3 |
| PfSPZ Challenge3200 P. falciparum Sporozoites by direct venous inoculation (DVI) | Biological | P218 100 mg (Oral Capsules) - Cohort 3, P218 1000 mg (Oral Capsules) - Cohort 2, P218 Placebo Oral Capsule - Cohort 3, P218 Placebo Oral Capsules - Cohort 2 |
Primary outcome
Cohort 1: Number of TEAEs
Time frame: 9 days
Incidence, severity and relationship to the treatment of observed or self-reported treatment emergent adverse events (TEAEs) after two single doses of 1000 mg P218 administered 48 hours apart in healthy adult volunteers.
Cohorts 2 and 3: Geometric Mean Time From PfSPZ Challenge to First Quantitative Polymerase Chain Reaction (qPCR) Outcome Equal or Greater Than 250 Asexual Parasites Per mL of Blood
Time frame: Number of days from PfSPZ Challenge DVI to positive parasitaemia, or 28 days
Chemoprotective activity of two single doses of 1000 mg P218 administered 2 hours after PfSPZ Challenge and 48 hours later in healthy adult volunteers
7 secondary outcomes
Cohorts 2 and 3: Number of P218 TEAEs
Time frame: 35 days
Cohorts 2 and 3: Number of PfSPZ Challenge TEAEs
Time frame: 35 days
Cohorts 2 and 3: Malaria Clinical Score at the Time of Introduction of Rescue Therapy
Time frame: On the day of positive parasitaemia or on Day 28
Cohorts 1, 2 and 3: P218 AUC[0-48h] - Day 1
Time frame: 9 days
Cohort 1: P218-beta-acyl-glucuronide-OH AUC[48-96h]
Time frame: 9 days
Cohorts 1, 2 and 3: P218 Cmax - Day 1
Time frame: 9 days
Cohorts 1, 2 and 3: P218 Tmax - Day 1
Time frame: 9 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Cristina Donini, PhD study director
MMV
Pieter-Jan Berghmans, MD principal investigator
SGS Belgium NV
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing P218 (1000 mg) Oral Capsules, P218 (100 mg) Oral Capsules and PfSPZ Challenge in people with Malaria, run by Medicines for Malaria Venture at 1 site in Belgium.
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 0 inclusion and 10 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 9 Apr 2021. 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 Belgium. 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. 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?
Yes. Results are posted in the registry (first posted 9 Apr 2021). 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?
Cohort 1: Number of TEAEs (time frame: 9 days). 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?
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 9 Apr 2021.