A Phase Ib, Randomized, Double-Blind, Placebo Controlled, Sequential Study of Single Oral Doses of M5717 to Explore the Chemoprophylactic Activity of M5717 in a Controlled Plasmodium falciparum Sporozoite Challenge Model in Healthy Participants

Completed

• Conditions: malaria; 10014142

• Registration Number: NL-OMON49971
• Lead Sponsor: Merck

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

Age
1. Are between 18 and 45 years of age at the time of signing the informed
consent.
Type of Participant and Disease Characteristics
2. Are overtly healthy as determined by medical evaluation, including no
clinically significant abnormality identified on physical examination or
laboratory evaluation and no active clinically significant disorder, condition,
infection or disease that would pose a risk to participant safety or interfere
with the study evaluation, procedures or completion.
Weight
3. Have a body weight within 50 to 100 kg and body mass index within the range
19.0 to 29.9 kg/m2 (inclusive).
Sex
4. Are male or female
Contraceptive use by males or females will be consistent with local regulations
on contraception methods for those participating in clinical studies.
* Male Participants:
Agree to the following during the study intervention period and for at least
120 days after the day of the study intervention dose (covering a full sperm
cycle of 90 days starting after 5 half-lives of last dose of study intervention:
* Refrain from donating sperm
PLUS, either:
* Abstain from intercourse with a woman of childbearing potential
OR
* Use a male condom:
* When having sexual intercourse with a woman of childbearing potential, who is
not currently pregnant, and advise her to use a highly effective contraceptive
method with a failure rate of < 1% per year, as described in Appendix 3
Contraception, since a condom may break or leak.
* Female Participants:
* Have a negative serum test at Screening and a highly sensitive urine
pregnancy test within 24 hours before the first study intervention (DVI) and
within 24 hours before the second study intervention (M5717) administration, as
required by local regulations. [If a urine test cannot be confirmed as negative
(e.g., an ambiguous result), a serum pregnancy test is required. In such cases,
the participant must be excluded from participation if the serum pregnancy
result is positive].
* Are not pregnant or breastfeeding, and at least one of the following
conditions applies:
* Not a woman of childbearing potential
* At least 1 year post-menopausal (amenorrhea * 12 months and
follicle-stimulating hormone (FSH) * 40 mIU/mL) at Screening;
* Surgically sterile (bilateral oophorectomy, hysterectomy or bilateral
salpingectomy; tubal ligation alone is not sufficient).
OR
* If a woman of childbearing potential, use a highly effective contraceptive
method (i.e., with a failure rate of < 1% per year), preferably with low user
dependency, as described in Appendix 3 for the following time periods:
* Before the first dose of the study intervention(s), if using hormonal
contraception:
* Has completed at least one 4-week cycle of an oral contraception pill and
either had or has begun her menses
OR
* Has used a depot contraceptive or extended-cycle oral contraceptive for at
least 28 days and has a documented negative pregnancy test using a highly
sensitive assay.
* During the intervention period
* After the study intervention period (i.e., after the last dose of study
intervention is administered) for at least 62 days, corresponding to the time
needed to eliminate any study intervention(s) (5 times terminal half-live of
155 hours) plus 30 days (a menstrual cycle) after the last dose of study
i

Exclusion Criteria

Medical Conditions
1. 12-Lead electrocardiogram (ECG) outside normal range (QTcF > 450 ms, PR
interval > 215 ms, or QRS > 120 ms) and deemed clinically relevant by the
Investigator.
2. Supine systolic blood pressure > 140 or < 90 mmHg, diastolic blood pressure
> 90 or < 50 mmHg, and pulse rate > 90 or < 50 beats per minute (min) at
Screening and at Admission on Day -1 (Any abnormal blood pressure or pulse rate
results may be repeated once and if the repeat result is within the normal
range, it is not considered to have met the exclusion criterion).
3. Seropositive for human immunodeficiency virus (HIV) I and II antibody or
antigen), hepatitis B virus (HBV; hepatitis B surface antigen [HBsAg]), or
hepatitis C virus (HCV; antibody) tests.
4. Liver function tests (see Appendix 5 Liver Safety: Suggested Actions and
Follow-up Assessments) above the upper limit of normal (ULN) (> 3xULN) (as
specified in the Laboratory Manual) the day before DVI / study intervention
administration (Day -1).
5. History or presence of diagnosed food or known drug allergies (including but
not limited to allergy to any of the antimalarial rescue medications to be used
in the study), or history of anaphylaxis or other severe allergic reactions.
Note: Participants with seasonal allergies/hay fever, house dust mite allergy,
or allergy to animals that are untreated and asymptomatic at the time of dosing
can be enrolled in the study.
6. History of a serious psychiatric condition that may affect participation in
the study or preclude compliance with the protocol.
7. Any surgical or medical condition possibly affecting drug absorption (e.g.
cholecystectomy, gastrectomy, bowel disease), distribution, metabolism or
excretion.
8. Any history of gallbladder disease, including cholecystitis and/or
cholelithiasis.
9. Any condition that in the opinion of the investigator would jeopardize the
safety or rights of a person participating in the study or would render the
person unable to comply with the protocol.
10. Frequent headaches of clinical relevance and/or migraine, recurrent nausea,
and/or vomiting (> 2 times per month).
11. Ingestion of any poppy seeds within 24 hours prior to each Drug Abuse
Screening.
12. Personal history of malaria or medical history of possible exposure to
malaria.
13. Presence of acute infectious disease or fever (i.e., sublingual temperature
* 38.0°C) within the 5 days prior to DVI with malaria sporozoites.
Prior/Concomitant Therapy
14. Use of medications known to interact with atovaquone-proguanil (Malarone)
or artemether-lumefantrine (Riamet) such as cimetidine, metoclopramide or
antacids, or an anticipated requirement for the use of these at any point
during the study period (see also Section 5.1).
15. Use of systemic antibiotics with known antimalarial activity within 30 days
(or 5 half-lives whichever is longer) of first study intervention
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.
16. Use of any prescription drugs, herbal supplements (e.g., St John's Wort) or
over-the-counter medication within 7 days or five half-lives (whichever is
longer) prior to the first study intervention ad

Study & Design

• Study Type: Interventional
• Study Design: Not specified