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Chemoprophylactic Activity of M5717 in Plasmodium Falciparum Sporozoite (PfSPZ) Challenge Model

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ClinicalTrials.gov Identifier: NCT04250363
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : October 22, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Brief Summary:
The main purpose of this study is to assess the chemoprophylactic activity and dose-exposure-response relationship of single oral dose of M5717 administered after direct intravenous inoculation (DVI) of Plasmodium falciparum sporozoite (PfSPZ) challenge in healthy participants.

Condition or disease Intervention/treatment Phase
Healthy Drug: M5717 Biological: PfSPZ Challenge Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : February 17, 2020
Estimated Primary Completion Date : May 30, 2021
Estimated Study Completion Date : May 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: M5717
Participants will receive single ascending oral dose of M5717 powder in capsule after DVI of PfSPZ challenge on Day 1 (early liver stage) or on Day 4 (late liver stage).
Drug: M5717
Participants will receive single ascending oral dose of M5717 powder in capsule on Day 1 (early liver stage) or on Day 4 (late liver stage).

Biological: PfSPZ Challenge
Participants will receive 3200 units of Plasmodium falciparum sporozoites by DVI.

Placebo Comparator: Placebo
Participants will receive placebo matched to M5717 after DIV of PfSPZ challenge on Day 1 (early liver stage) or on Day 4 (late liver stage).
Biological: PfSPZ Challenge
Participants will receive 3200 units of Plasmodium falciparum sporozoites by DVI.

Drug: Placebo
Participants will receive placebo matched to M5717 on Day 1 (early liver stage) or on Day 4 (late liver stage).




Primary Outcome Measures :
  1. Number of Participants With Positive Parasitemia [ Time Frame: From Day 1 up to Day 28 ]
    Positive parasitemia is defined as first positive quantitative polymerase chain reaction (qPCR) outcome equal or greater than 100 asexual parasites per milliliter (mL) of blood within 28 days of PfSPZ challenge.

  2. Time to Parasitemia [ Time Frame: From Day 1 up to Day 28 ]
    Time to parasitemia is defined as time from PfSPZ DIV to the first qPCR outcome equal or greater than 100 asexual parasites per mL of blood.

  3. Number of Participants With Documented Blood Stage Parasite Growth [ Time Frame: From Day 1 up to Day 28 ]
    Blood stage parasite growth is defined as an increase of qPCR measured asexual parasites per mL compared to the first parasitemia measurement.

  4. Clinical Symptoms of Malaria Using Malaria Clinical Score [ Time Frame: From Day 1 up to Day 28 ]
  5. Number of Participants With Dose Exposure Response Relationship of M5717 Assessed by Pharmacokinetic/Pharmacodynamic Modeling [ Time Frame: From baseline up to Day 28 ]

Secondary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related Adverse Events [ Time Frame: Baseline up to end of study visit (approximately 33 days) ]
  2. Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters, Vital Signs and 12-lead Electrocardiogram (ECG) Findings [ Time Frame: Baseline up to end of study visit (approximately 33 days) ]
    Number of participants with clinically significant change from baseline in safety laboratory parameters, vital signs and 12-lead ECG findings will be reported.

  3. Area Under the Blood Concentration Concentration-Time Curve (AUC) After Single Dose Administration of M5717 [ Time Frame: Pre-dose up to 768 hours post-dose ]
  4. Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 [ Time Frame: Pre-dose up to 768 hours post-dose ]
  5. Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717 [ Time Frame: Pre-dose up to 768 hours post-dose ]
  6. Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 [ Time Frame: Pre-dose up to 24 hours post-dose ]
  7. Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 [ Time Frame: Pre-dose up to 168 hours post-dose ]
  8. Maximum Observed Blood Concentration (Cmax) of M5717 [ Time Frame: Pre-dose up to 768 hours post-dose ]
  9. Blood Concentration at 24 Hours (C24) of M5717 [ Time Frame: 24 hours post-dose ]
  10. Blood Concentration at 168 Hours (C168) of M5717 [ Time Frame: 168 hours post-dose ]
  11. Time to Reach Maximum Blood Concentration (tmax) of M5717 [ Time Frame: Pre-dose up to 24 hours post-dose ]
  12. Apparent Terminal Half-life (t1/2) of M5717 [ Time Frame: Pre-dose up to 768 hours post-dose ]
  13. Elimination Rate Constant (lambda z) of M5717 [ Time Frame: Pre-dose up to 768 hours post-dose ]
  14. Apparent Total Body Clearance From Blood (CL/f) of M5717 [ Time Frame: Pre-dose up to 768 hours post-dose ]
  15. Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of M5717 [ Time Frame: Pre-dose up to 768 hours post-dose ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participants who 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
  • Participants who have a body weight within 50 to 100 kilograms (kg) and body mass index within the range 19.0 to 29.9 kilograms per meter square (kg/m2) (inclusive)
  • Male participants, 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 (WOCBP) or - use a male condom, when having sexual intercourse with a WOCBP, who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of less than (<) 1 percent (%) per year, since a condom may break or leak
  • Female participants who are: - not a WOCBP; - at least 1 year post-menopausal (amenorrhea greater than or equal to [>=] 12 months and follicle-stimulating hormone [FSH] >= 40 milli-international units per milliliter [mIU/mL]) at screening; - surgically sterile (bilateral oophorectomy, hysterectomy or bilateral salpingectomy; tubal ligation alone is not sufficient)
  • Participants who are capable of giving signed informed consent, which includes compliance with the requirements (including mandatory intake of rescue medication to participants who have been administered the investigational Plasmodium falciparum sporozoite challenge) and restrictions listed in the informed consent form (ICF) and this protocol
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Participants with 12-Lead electrocardiogram (ECG) outside normal range (QTcF greater than [>] 450 milli seconds [ms], pulse rate [PR] > 215 ms, or QRS > 120 ms) and deemed clinically relevant by the Investigator
  • Supine systolic blood pressure > 140 or < 90 millimeter of mercury (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)
  • 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
  • Liver function tests above the upper limit of normal (ULN) (> 3 x ULN) the day before DVI / study intervention administration (Day -1)
  • 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
  • Participant with a whole blood donation or loss of > 450 mL within 60 days before administration of study drug or unwilling to defer blood donations for 6 months
  • Other protocol defined exclusion criteria could apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04250363


Contacts
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Contact: Communication Center +496151725200 service@emdgroup.com

Locations
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Netherlands
Leiden University Medical Center Recruiting
Leiden, Netherlands
Sponsors and Collaborators
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Additional Information:
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Responsible Party: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT04250363    
Other Study ID Numbers: MS201618_0003
2019-003414-14 ( EudraCT Number )
First Posted: January 31, 2020    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany:
Healthy Participants
M5717
Malaria
Plasmodium falciparum
Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases