Clinical Trials/NCT02661373

NCT02661373

Completed

Phase 1

Phase 1a, First-In-Human, Dose-Escalation Study of (+)-SJ000557733 (SJ733), an Oral, Novel Inhibitor of Plasmodium Falciparum Plasma Membrane Protein PfATP4

St. Jude Children's Research Hospital1 site in 1 country44 target enrollmentMarch 1, 2016

ConditionsMalaria

InterventionsSJ733 Cobicistat

DrugsSJ733 Cobicistat

Overview

Phase: Phase 1
Intervention: SJ733
Conditions: Malaria
Sponsor: St. Jude Children's Research Hospital
Enrollment: 44
Locations: 1
Primary Endpoint: Maximum tolerated dose (MTD)
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Malaria is an infectious disease caused by a parasite that is passed to humans when an infected mosquito bites a person. About 3.4 billion people live in areas of the world where malaria is regularly found. In many countries, malaria is one of the leading causes of illness and death. Despite this, there are a limited number of drugs, called antimalarials, that can be used to treat malaria and increasing reports of resistance to existing antimalarials.

The purpose of this research study is to test a new experimental antimalarial drug called SJ733 to first assess its safety, tolerability and blood levels in healthy adult volunteers.

Single-dose, multi-dose and boosted-dose cohorts (both single and multi-dose) will be studied. The pharmacoenhancer (booster), cobicistat, will be given in combination with SJ733 in the boosted dose-cohorts.

PRIMARY OBJECTIVES:

To assess the preliminary safety and tolerability of escalating doses of antimalarial SJ733 in healthy human volunteers.
To investigate the pharmacokinetic (PK) profile of escalating doses of antimalarial SJ733 and its metabolite in healthy human volunteers.
To identify a dose of SJ733 that can be tested in a separate Phase 1b human malaria challenge study.
To assess the preliminary safety and tolerability of SJ733 in healthy adult volunteers after multiple oral dosing.
To assess the pharmacokinetics of SJ733 and its metabolite SJ506 after multiple dosing of SJ733 in healthy adult volunteers.
To assess the preliminary safety and tolerability of escalating single oral doses of SJ733 in combination with cobicistat among healthy adult volunteers.
To assess the pharmacokinetics of SJ733 and its metabolite SJ506 after single oral doses of SJ733 in combination with cobicistat among healthy adult volunteers.
To assess the preliminary safety and tolerability of SJ733 in combination with cobicistat in healthy adult volunteers after multiple oral dosing.
To assess the pharmacokinetics of SJ733 and its metabolite SJ506 after multiple dosing of SJ733 in combination with cobicistat among healthy volunteers.

SECONDARY OBJECTIVE:

To assess the impact of food intake on the pharmacokinetic profile of antimalarial SJ733.

Detailed Description

This is a single site, Phase 1a, first-in-human, oral, primarily single-dose, dose escalation study of (+)-SJ000557733 (SJ733) in healthy adult volunteers. SJ733, is an investigational oral anti-malarial agent is a novel inhibitor of Plasmodium falciparum plasma membrane protein (PfATP4). Subjects meeting eligibility criteria will be enrolled using a leap frog, fixed dose escalation design with an adaptive component where 6 subjects are enrolled per dose cohort. Following successful completion of the safety and pharmacokinetic (PK) assessment resulting from the single-dose escalation portion of the study, a three-dose cohort study will be undertaken. It includes once per day oral dosing for 3 consecutive days. Both single and multi-dose cohorts of SJ733 in combination with cobicistat (boosted cohorts) will also be completed. After the study results from the single-dose cohorts of SJ733 in combination with cobicistat (boosted cohorts) were reviewed, multi-dose cohorts of SJ733 in combination with cobicistat (boosted cohorts) were not conducted and Phase 2 study planning initiated.

Registry

clinicaltrials.gov

Start Date

March 1, 2016

End Date

March 9, 2018

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

St. Jude Children's Research Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Healthy adult (as certified by comprehensive medical assessment including detailed history and complete physical examination), male or female, aged 18 to 55 years of age (inclusive) at screening
•At least 50 kg in weight and body mass index (BMI) between 18 and 34 kg/m\^2
•Able and willing to provide informed consent and to be available for follow-up for the planned duration of the study
•If female, then not of child bearing potential (i.e. permanently sterilized hysterectomy or bilateral oophorectomy at least 6 months before screening; proper documentation required\] and/or post-menopausal defined as 12 months with no menses without an alternative cause and with an estradiol level of \< 30 pg/mL and follicle-stimulating hormone level of \> 40 IU/L at screening)
•Sexually active males must agree to be abstinent or use condoms for the duration of the study.
•Screening laboratories (hematology, chemistries, venous methemoglobin level specified in schedule of evaluations) within normal institutional range or if outside the range, not clinically significant in the opinion of the investigator.
•Inclusion Criteria for Participants in Single-dose Cohort Only::
•Agrees not to receive any vaccination within 7 days prior to Day 0 and through Day
•Agrees not to use nonprescription drugs, including vitamins, antacids, and herbal and dietary supplements within 7 days prior to Day 0 and through Day
•Acetaminophen may be used at doses of ≤ 1 g/day, and ibuprofen may be used at doses of ≤ 1.2 g/day.

Exclusion Criteria

•Presence of a significant medical or psychiatric condition that in the opinion of the investigator precludes participation in the study.
•Clinically significant abnormalities on physical examination that, in the opinion of the investigator, would preclude entry into the study.
•History of having a significant illness within the 2 weeks prior to screening visit. Participants can screen after illness is resolved for two weeks.
•History of clinically significant electrocardiogram abnormalities or clinically significant abnormalities from the screening electrocardiogram.
•G6PD deficiency
•History of hemolytic anemia or methemoglobinemia
•History of severe drug hypersensitivity including a severe allergic reaction, anaphylaxis or convulsions following any medication, vaccination or infusion.
•History of drug or alcohol abuse in the 12 months prior to screening or evidence at screening visit
•Use of nicotine containing products within 30 days prior to screening
•Positive blood test for HBsAg, HCV, or HIV-1

Arms & Interventions

Treatment Arm

Participants will receive SJ733, an investigational drug developed at St. Jude Children's Research Hospital, and cobicistat.

Intervention: SJ733

Treatment Arm

Participants will receive SJ733, an investigational drug developed at St. Jude Children's Research Hospital, and cobicistat.

Intervention: Cobicistat

Outcomes

Primary Outcomes

Maximum tolerated dose (MTD)

Time Frame: 7 days after the last dose administration

MTD is defined as the dose level prior to the dose cohort that 2 or more Grade 2 methemoglobinemia or anemia (attributed to hemolysis) OR any related Grade 3 OR any Grade 4, study drug adverse event (AE) occurred in.

Dose limiting toxicity (DLT)

Time Frame: From baseline up to minimum of 7 days post-dose

Number of DLT events will be described at each study dose level. DLT is defined as possibly, probably, or definitely related Grade 4 event, possibly, probably or definitely related Grade 3 event, or possibly, probably, or definitely related Grade 2 methemoglobinemia or anemia (attributed to hemolysis) events.

Drug volume of distribution