Phase 1
N=16
Study in Blood Stage Malaria Infection After DVI of Cryopreserved P. Falciparum (NF54 Strain) Sporozoites
Malaria,Falciparum · Parasitemia · Protozoan Infections · Parasitic Disease
Bottom Line
View on ClinicalTrials.gov: NCT04310085 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Sep 2021
Primary outcome: Primary: Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related. — 13; 12; 1; 2 Incidence
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet (Drug); PfSPZ-DVI Challenge (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Medicines for Malaria Venture
- Primary completion
- Dec 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related. |
13; 12; 1; 2; 0; 0 | — |
| PRIMARY Change in Malaria Clinical Score From PfSPZ-DVI Challenge Until Parasite Clearance. |
9.63; 13.0 | — |
| PRIMARY Time to First PCR Positivity. |
9.76; 9.60 | — |
| PRIMARY Parasitaemia at First PCR Positivity |
367.2; 711.7 | — |
| PRIMARY Time to Parasitaemia of ≥5000 Parasites Per mL Blood (Cohorts 1 and 2) |
11.19; 11.46 | — |
| PRIMARY Parasitaemia at the Time Parasitaemia ≥5000 Parasites Per mL Blood (Cohorts 1 and 2) |
12807.4; 18831.7 | — |
| PRIMARY Time to First Dose of Treatment With Artemether-lumefantrine (Riamet®) (Cohorts 1 and 2) |
12.09; 12.04 | — |
| PRIMARY Parasitaemia at First Dose of Treatment With Riamet® (Cohorts 1 and 2) |
3936.7; 9454.3 | — |
| PRIMARY Incidence of Positive PCR and Parasitaemia of ≥5000 Parasites Per mL Blood. |
8; 8 | — |
Summary
This is a single-centre, open-label, Phase Ib study designed to assess if intravenous injection of approximately 3200 P. falciparum (NF54 strain) sporozoites can be safely administered to achieve blood-stage parasitaemia with a kinetics/PCR profile that will allow for the future characterisation of antimalarial blood-stage activity of new chemical entities in a relatively small number of participants during early drug development.
Healthy, malaria-naïve adults, aged 18-55 years, will be enrolled in a maximum of 2 cohorts. Enrolment into the cohorts will proceed sequentially, with two target levels of parasitaemia, i.e., 5000 parasites/mL blood in Cohort 1 and 10000 parasites/mL blood in Cohort 2.
(Based on observed levels of parasitaemia in Cohort 1, the target threshold for treatment in Cohort 2 was maintained at 5,000 p/mL (vs 10,000 p/mL in the protocol)).
The 3-day antimalarial therapy regimen will be further administered and monitored until parasite clearance. Safety and tolerability will be monitored during the whole study duration.
Eligibility Criteria
Inclusion Criteria
- Informed Consent Form signed voluntarily before any study-related procedure is performed, indicating that the participant understands the purpose of and procedures required for the study and is willing to participate in the study, including administration of registered antimalarial therapy;
- Male or female, between 18 and 55 years old (extremes included) at screening;
- Body weight of at least 50 kg and a body mass index (BMI) of 19.0 to 30.0 kg/m2 (extremes included);
- Good general health without clinically relevant medical illness, physical exam findings including vital signs, and laboratory abnormalities (e.g., without liver transaminases >1x ULN and according to the clinically acceptable ranges for study inclusion laboratory tests in Attachment 4) as determined by the Investigator;
- Willing to adhere to the prohibitions and restrictions specified in this protocol (see Section 4.3), including willingness to stay confined to the inpatient unit for the required duration and willingness to avoid travelling outside of Benelux during the study period;
- Female participants should fulfil one of the following criteria:
- At least 1 year postmenopausal (amenorrhea >12 months and follicle-stimulating hormone [FSH] >30 mIU/mL) prior to screening;
- Surgically sterile (bilateral oophorectomy, hysterectomy or bilateral salpingectomy);
- Will use contraceptives as outlined in inclusion criterion 7;
- Female participants of childbearing potential (excluding females with female partners) must agree to the use of a highly effective method of birth control from the screening visit until 40 days after the EOS visit at Day 28 (covering a full menstrual cycle of 30 days starting after 5 half-lives of last dose of Riamet®); Note: Highly effective birth control methods include: combined (oestrogen- and progestogen-containing) oral/intravaginal/transdermal hormonal contraception associated with inhibition of ovulation, progestogen-only oral/injectable/implantable hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence from heterosexual intercourse.
- Female participant has a negative pregnancy test at screening and upon admission in the clinical unit; Note: Pregnancy testing will consist of serum β-human chorionic gonadotropin (β-HCG) tests at screening and at the EOS visit and a urine β-HCG tests on Day -1, in all women.
- Different ways of being reachable 24/7 (e.g., by mobile phone, regular phone or electronic mail) during the whole study period.
Exclusion Criteria
- 1. Nursing (lactating) women; 2. Participation in any other clinical drug or vaccine study within 30 days (or 5 half-lives for drugs) preceding the day of PfSPZ-DVI Challenge (whichever is longer), or plans to participate in other investigational drug or vaccine research during the study period; 3. Participants who took standard vaccinations within 3 months before the start of the study or are planning to take standard vaccinations during the study period up to 8 weeks after PfSPZ-DVI Challenge; 4. Blood product donation to any blood bank during the 8 weeks (whole blood) or 4 weeks (plasma and platelets) prior to admission in the clinical unit on Day -1; 5. Mean ECG outside normal range and deemed clinically relevant by the Investigator. Examples of clinically significant ECG abnormalities for this study include:
- PR-interval >220 ms;
- QRS-complex >120 ms;
- Absolute QT greater than >500 ms;
- QT interval corrected according to Bazett's formula (QTcB) or QTcF >450 ms for male participants, >470 ms for female participants;
- Pathologic Q wave;
- Significant ST-T wave changes;
- Left or right ventricular hypertrophy;
- Non-sinus rhythm except isolated premature atrial contractions and ventricular extrasystole 21 units per week for males and >14 units per week for females where one alcohol unit is defined
Data sourced from ClinicalTrials.gov (NCT04310085). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.