Safety, Tolerability and Chemoprotective Activity of P218 in PfSPZ Challenge Model
Source: ClinicalTrials.gov NCT03707041 ↗Summary
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort 1: Number of TEAEs |
2; 1; 4; 1 | — |
| PRIMARY 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 |
28.000; 25.822; 10.615 | — |
| SECONDARY Cohorts 2 and 3: Number of P218 TEAEs |
1; 0; 0; 8; 9; 6 | — |
| SECONDARY Cohorts 2 and 3: Number of PfSPZ Challenge TEAEs |
9; 1; 6; 0; 8; 0 | — |
| SECONDARY Cohorts 2 and 3: Malaria Clinical Score at the Time of Introduction of Rescue Therapy |
0.00; 0.00; 1.00 | — |
| SECONDARY Cohorts 1, 2 and 3: P218 AUC[0-48h] - Day 1 |
16752; 13865; 1296 | — |
| SECONDARY Cohort 1: P218-beta-acyl-glucuronide-OH AUC[48-96h] |
27283 | — |
| SECONDARY Cohorts 1, 2 and 3: P218 Cmax - Day 1 |
7482; 7241; 856 | — |
| SECONDARY Cohorts 1, 2 and 3: P218 Tmax - Day 1 |
1.00; 1.00; 1.00 | — |
Eligibility Criteria
Subjects meeting all of the following criteria are eligible to participate in this study:
- Informed Consent Form signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study, including administration of rescue treatment.
- Male or female, between 18 and 45 years old (extremes included) at screening.
- Body weight of at least 50 kg and a body mass index (BMI) of 19 to 30 kg/m2 (extremes included).
- Good general health without clinically relevant medical illness, physical exam findings including vital signs, and laboratory abnormalities as determined by the investigator.
- Willing to adhere to the prohibitions and restrictions (see Section 4.3) specified in this protocol, including willingness to stay confined to the inpatient unit for required duration and willingness to avoid to travel outside of Benelux during the study period.
- Female subjects should fulfil one of the following criteria:
- At least 1 year post-menopausal (amenorrhea >12 months and follicle-stimulating hormone (FSH) >30 mIU/mL) prior to screening;
- Surgically sterile (bilateral oophorectomy, hysterectomy or tubal ligation);
- Will use contraceptives as outlined in inclusion criteria 7 and 8.
- Female subjects of childbearing potential must agree to the use of a highly effective method of birth control from screening visit to until 40 days after the last dose of IMP (covering a full menstrual cycle of 30 days starting after 5 half-lives of last dose of IMP).
Note: Highly effective birth control methods include: combined (estrogen 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.
- Male subjects who are sexually active with a female partner of childbearing potential must agree to the use of an effective method of birth control from the day of the first IMP dose until 100 days thereafter (covering a full sperm cycle of 90 days starting after 5 half-lives of last dose of IMP).
Note: Medically acceptable methods of contraception that may be used by the subject and/or partner include sterilization and vasectomy or a double barrier option combining oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device or etonogestrel implant.
- Female subject has a negative pregnancy test at screening and upon admission in the clinical unit.
Note: Pregnancy testing will consist of a serum β-human chorionic gonadotropin (β-HCG) test at screening and urine β-HCG tests at other visits, in all women.
Inclusion Criteria - CHMI (controlled human malaria infection) specific:
- Different ways of being reachable 24/7 (e.g. by mobile phone, regular phone or electronic mail) during the whole study period.
Subjects meeting any of the following criteria are excluded from participation in this study:
- Nursing (lactating) women.
- Participation in any other clinical drug or vaccine study within 30 days (or five half-lives for drugs) preceding the first dose of IMP (whichever is longer), or plans to participate in other investigational drug or vaccine research during the study period.
- 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.
- 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;
- QT interval corrected according to Bazett's formula (QTcB) or QT interval corrected according to Fridericia's formula [3] (QTcF) >450 ms;
- Pathologi
Data sourced from ClinicalTrials.gov (NCT03707041). 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. Informational only — not medical advice.