Clinical trial NCT04709692
Conditions: Malaria, Falciparum Malaria, Vivax
Sponsor: R. Kiplin Guy
Start date: 2021-04-14; Completion date: 2022-04-15
Enrollment: 22 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This Phase 2a trial recruits adult patients with uncomplicated P. vivax or P. falciparum blood-stage malaria mono-infection. The study drug SJ733 will be administered to examine its antimalarial efficacy, safety, and tolerability. This study also evaluates whether or not a fixed dose of the pharmacoenhancer cobicistat when given in combination with SJ733 significantly improves drug efficacy.

Detailed description:
This is an adaptive open label Phase 2a study to examine the antimalarial efficacy, safety, and tolerability of SJ733 in adult patients with uncomplicated P. vivax or P. falciparum blood-stage malaria monoinfection. SJ733 will be administered orally once every day for three consecutive days, with or without a fixed dose of the pharmacoenhancer cobicistat. The Phase 1 clinical data (completed under a US IND) and PK/PD models suggest that SJ733 is most likely to be curative as a 3-daily-dose pharmacoenhanced therapy, due to its moderately rapid clearance. There will be 1-3 cohorts with each cohort containing two treatment arms, P. falciparum (a) and P. vivax (b). Cohort progression will be managed independently for each treatment arm. Interim analysis will determine whether the data for a given treatment arm meets the success criteria, is inconclusive, or meets the failure criteria. Antimalarial efficacy will be examined over the period of 42 days. Additional aims are to characterize the safety and pharmacokinetics of SJ733. The results of this trial will identify active, well-tolerated doses for investigation in a larger Phase 2b clinical trial.

Arms: arm 1: Combination of 600 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.vivax arm 2: Combination of 600 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.falciparum arm 3: 600 mg SJ733 administered orally once every day for three consecutive days for patients with P.vivax arm 4: 600 mg SJ733 administered orally once every day for three consecutive days for patients with P.falciparum arm 5: Combination of 300 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.vivax arm 6: Combination of 300 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.falciparum
Interventions: intervention 1: (+)-SJ000557733 (SJ733)
Intervention descriptions: intervention 1: Anti-Malarial

Protocol documents:
Prot_SAP_ICF_001.pdf: 
Document Coversheet 
 Study Title: An Open Label Phase 2a Study to Assess the Efficacy, Safety, Tolerability, and 
Pharmacokinetics of (+)-SJ000557733 (SJ733) With or Without Cobicistat in Adult Patients With 
Acute, Uncomplicated Malaria Over a 42 Day Period 
Institution/Site: 
University of Kentucky 
Document (Approval/Update) Date: 
11/2/2020 
NCT Number: 
NCT04709692 
IRB Number 
53333 


PROTOCOL TYPE
Which IRB
Medical
NonMedical
Protocol Process Type
Exemption
Expedited
Full
(Must be risk level 1)
 
IMPORTANT NOTE: Once you have saved your choices under "Which IRB" and "Protocol Process Type", you will not be
able to change your selections. If you select the wrong IRB Type and/or your application is deemed eligible for a different
Protocol Process Type, it may be necessary to create a new application. 
Please see below for guidance on which selections to make, and/or go to ORI's "Getting Started" web page. If you still have questions
about which IRB or Protocol Process Type to choose, please contact the Office of Research Integrity (ORI) at 859-257-9428 prior to
saving your selections.
 
*Which IRB*
The Medical IRB reviews research emanating from the Colleges of Dentistry; Health Sciences; Medicine; Nursing; Pharmacy and
Health Sciences; and Public Health.
The Nonmedical IRB reviews research originating from the Colleges of Agriculture; Arts & Sciences; Business & Economics;
Communication & Information; Design; Education; Engineering; Fine Arts; Law; and Social Work. The Nonmedical IRB does not review
studies that involve administration of drugs, testing safety or effectiveness of medical devices, or studies that involve invasive medical
procedures, regardless of from what college the application originates. 
*Which Protocol Process Type* 
Under federal regulations, an investigator's application to conduct a research project involving human subjects can be processed by the
IRBs in three ways: 
by full review;
by exemption certification;
by expedited review.
The preliminary determination that a research project is eligible for exemption certification or expedited review is made by the
investigator. For assistance in determining which review process type your IRB application is eligible for, please go to ORI's "Getting
Started" web page.
 
The revised Common Rule expanded exemption certification category 4 for certain secondary research with
identifiable information or biospecimens. The regulations no longer require the information or biospecimens to be
existing.  For more information see the Exemption Categories Tool.
 
Section 1 Page 1 of 1
IRB Approval
11/2/2020
IRB # 53333
IRB1


PROJECT INFORMATION
Title of Project: (If applicable, use the exact title listed in the grant/contract application). *** Effective 4/16/2020: If your research
involves investigating any aspect of COVID-19, please enter "COVID19" at the start of your Project and Short Titles *** 
An Open Label Phase 2a Study to Assess the Efficacy,
Safety, Tolerability, and Pharmacokinetics of (+)-
SJ000557733 (SJ733) with or without Combination with
Cobicistat in Adult Patients with Acute, Uncomplicated
Plasmodium Falciparum or Vivax Malaria Mono-Infection
over a 42 Day Period
Short Title Description 
Note: "Short Title" should consist of a couple key words to easily identify your study - these key words (rather than the whole title) will
be displayed on the Dashboard in the listing for your study.
SJ733 Phase 2a
Anticipated Ending Date of Research Project: 
Number of human subjects (or records/specimens reviewed) 
60
Study is/will be open to new subject enrollment or data/specimen collection: 
Yes
No
6/30/2022
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PI CONTACT INFORMATION
The Principal Investigator's (PI) contact information is filled in automatically based on who was logged in when the application was
created (with LinkBlue ID). If research is being submitted to or supported by an extramural funding agency such as NIH, a private
foundation or a pharmaceutical/manufacturing company, the PI listed on the grant application or the drug protocol must be the same
person listed below. 
If you are not the Principal Investigator, do NOT add yourself as study personnel. You may change the PI contact information on an
application that is in Researcher edit mode by:
clicking the "Change Principal Investigator" link below;
searching for the PI's name using the search feature;
clicking "Select" by the name of the Principal Investigator, then "Save Contact Information".
You will automatically be added as study personnel with edit authorization so you can continue editing the application. 
Please fill in any blank fields with the appropriate contact information (gray shaded fields are not editable). Required fields left blank will
be highlighted in pink after you click "Save".
To change home and work addresses, go to myUK and update using the Employee Self Service (ESS) portal. If name has changed,
the individual with the name change will need to submit a 'Name Change Form' to the Human Resources Benefits Office for entering
into SAP. The new name will need to be associated with the individual's Link Blue ID in SAP before the change is reflected in E-IRB.
Contact the HR Benefits Office for additional information.
Note: Principal Investigator (PI) role for E-IRB access
The PI is the individual holding primary responsibility on the research project with the following permissions on the E-IRB application:
1. Read; 
2. write/edit;
3. receive communications; and 
4. submit to the IRB (IR, CR, MR, Other Review*). 
Change  Principal Investigator:
First Name: Rodney
Room# &
Bldg: 214H Lee T. Todd, Jr.
Building, 789 S.
Limestone
Last Name: Guy
Speed
Sort#: 
0596
Middle Name K
Department:
Dept Code: 7K300
 
PI’s
Employee/Student
ID#:
12217189
Rank: 
Dean and Professor
 
PI's Telephone #: 8592577896
Degree: PhD
PI's e-mail
address: kip.guy@uky.edu
PI's FAX
Number: 8592572128
PI is R.N.
Yes
No
Trained: Yes
Date Trained 8/9/2018
Do you, the PI, have a significant financial interest related to your responsibilities at the University of Kentucky (that requires
disclosure per the UK administrative regulation 7:2)?
Yes
No
Pharmaceutical Sciences - 7…

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RISK LEVEL
Indicate which of the categories listed below accurately describes this protocol
(Risk Level 1) Not greater than minimal risk
(Risk Level 2) Greater than minimal risk, but presenting the prospect of direct benefit to individual subjects
(Risk Level 3) Greater than minimal risk, no prospect of direct benefit to individual subjects, but likely to yield generalizable
knowledge about the subject's disorder or condition.
(Risk Level 4) Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious
problem affecting the health or welfare of subjects.
*“Minimal risk” means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of
themselves from those ordinarily encountered in daily life or during the performance of routine physical or psychological
examination or tests [45 CFR 46.102(i)]
Download UK's guidance document on assessing the research risk for additional information on risk [PDF] 
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SUBJECT DEMOGRAPHICS
Age level of human subjects: (i.e., 6 mths.; 2yrs., etc..) 18 y to 70 y
Indicate the targeted/planned enrollment of the following members of
minority groups and their subpopulations
(Please note: The IRB will expect this information to be reported
at Continuation Review time):
Enter Numbers Only!
Ethnic Origin
#Male
#Female
American
Indian/Alaskan
Native:
Asian:
Black/African
American:
Hispanic/Latino:
Native
Hawaiian/Pacific
Islander:
White/Caucasian:
Other or
Unknown:
If unknown, please
explain why: The trial will be conducted in
Iquitos, Peru.
Patients will be recruited from
the community, local health-care
clinics, and post-secondary
educational institutions through
word-of-mouth, active
recruitment by study staff, and
self-referral in response to
advertisements. Verbal
permission will be sought at
private locations where
advertisements will be posted,
and a signed letter of
authorization will be obtained
from any performance site
where recruitment activities take
place. All recruitment materials
will be approved by the EC
before use. Advertisements will
indicate the nature of the study
and provide a phone number for
further information. Currently, the
recruitment sites include 14
villages that have health posts in
the districts of Iquitos, San Juan
Bautista, and Punchana. Some
are located along the road and
others at the edges of the rivers.
The distance by land or river to
the city of Iquitos is less than
1.5 hours, most less than 1
hour. In general, the people who
40
20
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live in these recruitment areas
are representative of the
general population that suffers
malaria in the Amazon region.
They are generally mestizo and
do not live in extreme poverty.
Their educational level includes
completion of primary or high
school.
Indicate the categories of subjects and controls to be included in the
study. Depending on the subject category applicable to your research
you may be required to complete additional forms. [Note, if the study
does not involve direct intervention or direct interaction with subjects,
(e.g., record-review research, outcomes registries), do not check mark
populations which the research does not specifically target. For
instance, a large record review of a diverse population may incidentally
include a prisoner or an international citizen, but, if the focus or intent of
the study has nothing to do with that status, you do not need to check
those category(ies).]
Check All That Apply (at least one item must be selected)
Children (individuals under
age 18)
Wards of the State (Children)
Emancipated Minors
Students
College of Medicine
Students
UK Medical Center
Residents or House Officers
Impaired Consent Capacity
Adults
Pregnant
Women/Neonates/Fetal
Material
Prisoners
Non-English Speaking
International Citizens
Normal Volunteers
Military Personnel and/or
DoD Civilian Employees
Patients
Appalachian Population
ADDITIONAL INFORMATION:
Please visit the IRB Survival Handbook
under the named topic:
Children/Emancipated Minors
Students as Subjects
Prisoners
Impaired Consent Capacity Adults:
Link to required Form
And/Or:
UKMC Residents or House Officers
[see requirement of GME]
Non-English Speaking [see
instructions for recruitment and E-IRB
Research Description section on
same topic]
International Citizens [HTML] (DoD
SOP may apply [PDF])
Military Personnel and/or DoD Civilian
Employees (DoD SOP may apply
[PDF])
Section 5 Page 2 of 3
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Traumatic brain injury or acquired brain
injury
Severe depressive disorders or Bipolar
disorders
Schizophrenia or other mental disorders
that
involve serious cognitive disturbances
Stroke
Developmental disabilities
Degenerative dementias
CNS cancers and other cancers with
possible CNS involvement
Late stage Parkinson’s Disease
Late stage persistent substance
dependence
Ischemic heart disease
HIV/AIDS
COPD
Renal insufficiency
Diabetes
Autoimmune or inflammatory disorders
Chronic non-malignant pain disorders
Drug effects
Other acute medical crises
The next questions involve assessment of the study relative to potential recruitment of subjects with impaired consent capacity (or
likelihood).
Check this box if your study does not involve direct intervention or direct interaction with
subjects (e.g., record-review research, secondary data analysis). (you will not need to answer
the impaired consent capacity questions)
Does this study focus on adult subjects with any of the clinical conditions listed below
that present a high likelihood of impaired consent capacity or fluctuations in consent
capacity? (see examples below)
Yes
No
If Yes, go to the following link and complete and attach the indicated form unless you are filing for an exemption
certification: https://ris.uky.edu/ori/oriforms/formt/Scale.asp
Examples of such conditions include:
Attachments
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INFORMED CONSENT/ASSENT PROCESS/WAIVER
For your informed consent attachment(s), please download the most up-to-date version listed in "All Templates" under the
APPLICATION LINKS menu on the left, and revise to be in accord with your research project.
Additional Resources:
Sample Repository/Registry/Bank Consent (Word)
Instructions for Proposed Informed Consent Document
Instructions for Proposed Assent Form
Consent/Assent Tips:
If you have multiple consent documents, be sure to upload each individually (not all in a combined file).
Changes to consent documents (e.g., informed consent form, assent form, cover letter, etc...) should be reflected in a
'tracked changes' version and uploaded separately with the Document Type "Highlighted Changes".
It is very important that only the documents you wish to have approved by the IRB are attached; DELETE OUTDATED
FILES -- previously approved versions will still be available in Protocol History.
Attachments that are assigned a Document Type to which an IRB approval stamp applies will be considered the
version(s) to be used for enrolling subjects once IRB approval has been issued. 
Document Types that do NOT get an IRB approval stamp are:
"Highlighted Changes",
"Phone Script", and
"Sponsor's Sample Consent Form".
How to Get the Informed Consent Section Check Mark
1. You must check the box for at least one of the consent items and/or check mark one of the waivers, then if
applicable attach the corresponding document(s) as a PDF (if open to enrollment).
2. If you no longer need a consent document approved (e.g., closed to enrollment), or, the consent document
submitted does not need a stamp for enrolling subjects (e.g., umbrella study, or sub-study), only check
mark the "Stamped Consent Doc(s) Not Needed".
3. After making your selection(s) be sure to scroll to the bottom of this section and SAVE your work!
Check All That Apply
Informed Consent Form (and/or Parental Permission Form)
Assent Form
Cover Letter (for survey/questionnaire research)
Phone Script
Informed Consent/HIPAA Combined Form
Debriefing and/or Permission to Use Data Form
Sponsor's sample consent form for Dept. of Health and Human Services (DHHS)-approved protocol
Stamped Consent Doc(s) Not Needed
Attachments
Attach Type
File Name
Informed ConsentHIPAA Combined FormPhase2a_Main_Consent_Cert_of_Translation.pdf
Informed ConsentHIPAA Combined FormPhase2a_PK_Consent_Cert_of_Translation.pdf
Informed ConsentHIPAA Combined FormSJ733_Phase2a_PK_Consent_v1.0_en.pdf
Informed ConsentHIPAA Combined FormSJ733_Phase2a_PK_Consent_v1.0_es.pdf
Informed ConsentHIPAA Combined FormSJ733_Phase2a_Main_Consent_v1.0_en.pdf
Informed ConsentHIPAA Combined FormSJ733_Phase2a_Main_Consent_v1.0_es.pdf
Request for Waiver of Informed Consent Process
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If you are requesting IRB approval for waiver of the requirement for the informed consent process, or alteration of some or
all of the elements of informed consent (i.e. medical record review, deception research, or collection of biological
specimens), complete Section 1 and Section 2 below.
Note: The IRB does not approve waiver or alteration of the consent process for greater than minimal risk research, except
for planned emergency/acute care research as provided under FDA regulations. Contact ORI for regulations that apply to
single emergency use waiver or acute care research waiver (859-257-9428).
SECTION 1.
Check the appropriate item:
I am requesting waiver of the requirement for the informed consent process.
I am requesting alteration of the informed consent process.
If you checked the box for this item, describe which elements of consent will be altered, and/or omitted, and justify the
alteration.
SECTION 2.
The IRB may consider your request provided that all of the following conditions apply to your research and are
appropriately justified. Explain in the space provided for each condition how it applies to your research.
a) The research involves no more than minimal risk to the subject.
b) The rights and welfare of subjects will not be adversely affected.
c) The research could not practicably be carried out without the requested waiver or alteration.
d) Whenever possible, the subjects or legally authorized representatives will be provided with additional pertinent
information after they have participated in the study.
e) If the research involves using or accessing identifiable private information or identifiable biospecimens, the research
could not practicably be carried out without using such information or biospecimens in an identifiable format.
Private information/specimens are “identifiable” if the investigator may ascertain the identity of the subject or if
identifiers are associated with the information (e.g., medical records). This could be any of the 18 HIPAA identifiers
including dates of service.
If not using identifiable private information or identifiable biospecimens, insert N/A below.
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Request for Waiver of Documentation of Informed Consent Process
If you are requesting IRB approval for waiver of the requirement for documentation of informed consent (i.e. telephone
survey or mailed survey, internet research, or certain international research), your research activities must fit into one of
three regulatory options:
1. The only record linking the participant and the research would be the consent document, and the principal risk would be
potential harm resulting from a breach of confidentiality (i.e., a study that involves participants who use illegal drugs).
2. The research presents no more than minimal risk to the participant and involves no procedures for which written consent
is normally required outside of the research context (i.e. a cover letter on a survey, or a phone script).
3. The participant (or legally authorized representative) is a member of a distinct cultural group or community in which
signing forms is not the norm, and the research presents no more than minimal risk to the subject and there is an
appropriate alternative mechanism for documenting that informed consent was obtained.
Select the option below that best fits your study, and explain in the space provided how your study meets the criteria for the
selected regulatory option. 
Note: The IRB cannot waive the requirement for documentation or alter the consent form for FDA-regulated research unless it
meets Option #2 below. FDA does not accept Option #1. 
Note: Even if a waiver of the requirement for documentation is approved by the IRB, participants must still be provided oral or
written (e.g., cover letter) information including all required and appropriate elements of consent so they have the knowledge
and opportunity to consider whether or not to participate. To help ensure required elements are included in your consent
document, please use the Cover Letter Template as a guide: English- [WORD], Spanish- [WORD] The cover letter
template was developed specifically for survey/questionnaire research; however, it may be useful as a guide for developing a
consent document for other types of research as well. 
Option 1
a) The only record linking the participant and the research would be the consent document:
b) The principal risk would be potential harm resulting from a breach of confidentiality (i.e., a study that involves
subjects who use illegal drugs).
Under this option, each participant (or legally authorized representative) must be asked whether (s)he wants to sign a
consent document; if the participant agrees to sign a consent document, only an IRB approved version should be
used.
Option 2
a) The research presents no more than minimal risk to the participant:
b) Involves no procedures for which written consent is normally required outside of the research context (i.e. a cover
letter on a survey, or a phone script):
Option 3
a) The subject (or legally authorized representative) is a member of a distinct cultural group or community in which
signing forms is not the norm.
b) The research presents no more than minimal risk to the subject.
c) There is an appropriate alternative mechanism for documenting that informed consent was obtained.
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STUDY PERSONNEL
Do you have study personnel who will be assisting with the research?
After selecting 'Yes' or 'No' you must save by hitting the 'Save Study Personnel Information' button. 
Yes
No
Manage Study Personnel
Identify other study personnel assisting in research project:
The individual listed as PI in the 'PI Contact Information' section should NOT be added to this section.
If the research is being completed to meet the requirements of a University of Kentucky academic program, the faculty advisor is also considered
study personnel and should be listed as such below. ***Residents and students who are PI’s are encouraged to designate at least one other individual
(e.g., faculty advisor) as a contact with an editor role (DP).***
Role: DP = Editor (individual can view, navigate, and edit the application for any review phase (IR, CR/FR, MR) or 'Other Review", and submit Other
Reviews on behalf of the PI.)
Role: SP = Reader (individual can view and navigate through the currently approved application only.)
To add an individual via the below feature, search for applicable personnel first, then click "select" by the listing for the person you want to add as study
personnel to your protocol. For each individual selected, be sure to specify responsibility in the project, whether authorized by the principal investigator to
obtain informed consent, AND denote who should regularly receive E-IRB notifications.
NOTE: Study personnel are required to receive human research protection (HSP) training before implementing any research procedures
(e.g., CITI). For information about mandatory training requirements for study personnel, visit UK’s FAQ's on Mandatory Training web page, or
contact ORI at 859-257-9428. If you have documentation of current HSP training other than that acquired through UK CITI, you may submit it
to ORI (Jen.Hill@uky.edu) for credit.
Study personnel assisting in research project: 
Last
Name
First
Name
Responsibility In
Project
Role
A
C
Contact
Degree
StatusFlag
(HSP)
(HSP)Date
Removed?
Last
Updated
SFI
Ashe
Laura
Study Coordinator
DP
N
N
CCRC
P
Y
06/23/2020
N
10/22/2019
N
Hammill
Jared
Project
Assistance/Support
DP
N
Y
PhD
P
Y
08/01/2019
N
08/06/2019
N
Orozco
Blanca
Project
Assistance/Support
DP
N
N
 
P
Y
06/09/2020
N
04/21/2020
N
Lambert
Kasandra
Project
Assistance/Support
SP
N
N
 
P
Y
09/23/2020
Y
06/01/2020
N
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RESEARCH DESCRIPTION
**!!!PLEASE READ!!!** Known Issue: The below text boxes do not allow symbols, web addresses, or special characters
(characters on a standard keyboard should be ok). If something is entered that the text boxes don't allow, user will lose
unsaved information.
Workaround(s):
Save your work often to avoid losing data.
Use one of the attachment buttons in this section, or under the Additional Information section to include the
information with your application. During the document upload process, you will be able to provide a brief description
of the attachment.
Background: Provide an introduction and background information. Describe past experimental and/or clinical findings leading to the
formulation of your study. For research involving investigational drugs, describe the previously conducted animal and human studies.
You may reference grant application/sponsor’s relevant protocol pages and attach as an appendix in the E-IRB "Additional Information"
section, however, a summary paragraph must be provided in the text box below. For research that involves FDA approved drugs or
devices, describe the FDA approved uses of this drug/device in relation to your protocol. Attach a copy of the approved labeling as a
product package insert or from the Physician’s Desk Reference in the applicable E-IRB "Study Drug" or "Study Device" section.
SJ733 is a new antimalarial drug candidate that has undergone single ascending dose, pharmacoboosted single ascending dose
(pharmacoenhancement with cobicistat), food effect single dose, and multiple ascending dose Phase 1 studies in healthy volunteers
to demonstrate safety, tolerability, and its pharmacokinetic profile. SJ733 has also been tested in a two-cohort single dose, Phase 1b,
human Induced Blood Stage Malaria (IBSM) challenge study. Overall, SJ733’s excellent tolerability and safety profile, combined with
its rapid antiparasitic effect, support its candidacy as an antimalarial therapy. The Phase 1 clinical data and PK/PD models suggest
that SJ733 is most likely to be curative as a 3-daily-dose pharmacoenhanced therapy, due to its moderately rapid clearance.
The present proof-of-concept Phase 2a trial will be an adaptive, open label study to examine the antimalarial efficacy, safety, and
tolerability of SJ733 in adult patients with uncomplicated P. vivax or P. falciparum blood-stage malaria monoinfection. SJ733 will be
administered orally once every day for three consecutive days, with or without a fixed dose of the pharmacoenhancer cobicistat, to
determine if pharmacoenhancement is required, and if significant improvements in drug efficacy are seen at higher total exposures of
SJ733. Success will be defined independently for each treatment arm at Day 14 as: 1) the absence of any repeated drug-related
serious adverse event; and 2) crude ACPR = 80% (equivalent to = 20% recurrence). Crude ACPR is defined as the absence of
microscopically determined parasitemia (thick smear), irrespective of axillary temperature, in patients who did not previously meet any
of the criteria of early treatment failure, late clinical failure, or late parasitological failure. Additional aims are to characterize the
antiparasitic activity, safety, tolerability, and pharmacokinetics of SJ733 over the period of 42 days. The results of this trial will help
identify effective, well-tolerated doses for investigation in combination with a partner drug within a Phase 2b clinical study.
Objectives: List your research objectives. You may reference grant application/sponsor’s relevant protocol pages and attach as an
appendix in the E-IRB "Additional Information" section, however, a summary paragraph must be provided in the text box below.
Primary Objectives: 
1) To determine the efficacy of SJ733 with or without combination with the pharmacoenhancer cobicistat, given once per day for
three-consecutive days by examining parasitemia 14-days after initiation of therapy for the treatment of uncomplicated P. 
vivax or P. falciparum malaria monoinfection.
2) To evaluate the safety and tolerability of SJ733, with or without combination with the pharmacoenhancer cobicistat, given once per
day for three-consecutive days in patients with P. falciparum and P. vivax malaria infection.
Secondary Objectives:
1) To assess the effect of the proposed three-day therapy on the signs and symptoms of P. vivax or P. falciparum malaria infection up
to Day 42
2) To assess the effect of the proposed three-day therapy on treatment outcomes in patients with P. vivax or P. falciparum malaria
infection at Days 28, 35, and 42 
3) To describe parasite clearance kinetics in patients with P. vivax or P. falciparum malaria infection
4) To describe the pharmacokinetics of SJ733 and its primary metabolite SJ506 during the three-day dosing period and for 7
additional days in patients with P. falciparum and P. vivax malaria infection.
Exploratory Objectives:
1) To assess the effect of the proposed three-day therapy on PCR adjusted outcomes in patients with P. vivax or P. falciparum
malaria infection:
a. With PCR-adjustment at Days 7, 14, 28, 35, and 42 (P. falciparum only)
b. PCR adjusted rates of recurrence (P. vivax or P. falciparum), up to Day 42.
Study Design: Describe the study design (e.g., single/double blind, parallel, crossover, etc.). Indicate whether or not the subjects will
receive placebo medication at some point in the research procedures. Also, indicate whether or not the subjects will be randomized in
this study. You may reference sponsor’s protocol pages and attach as an appendix in the E-IRB "Additional Information" section,
however, a summary paragraph must be provided in the text box below. (Including the study design table from a sponsor’s protocol is
Section 8 Page 1 of 20
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helpful to IRB members.)
Community-Based Participatory Research: If you are conducting community-based participatory research (CBPR), describe
strategies for involvement of community members in the design and implementation of the study, and dissemination of results from the
study.
Research Repositories: If the purpose of this submission is to establish a Research Repository (bank, registry) indicate whether the
material you plan to collect would or would not be available from a commercial supplier, clinical lab, or established IRB approved
research repository. Provide scientific justification for establishment of an additional repository collecting duplicate material. Describe
the repository design and operating procedures. For relevant information to include, see the UK Research Biospecimen Bank
Guidance [PDF] or the UK Research Registry Guidance [PDF]
The present proof-of-concept Phase 2a trial will be an adaptive, open label study to examine the antimalarial efficacy, safety, and
tolerability of SJ733 in adult patients with uncomplicated P. vivax or P. falciparum blood-stage malaria monoinfection. SJ733 will be
administered orally once every day for three consecutive days, with or without a fixed dose of the pharmacoenhancer cobicistat, to
determine if pharmacoenhancement is required, and if significant improvements in drug efficacy are seen at higher total exposures of
SJ733. Success will be defined independently for each treatment arm at Day 14 as: 1) the absence of any repeatable drug-related
serious adverse event; and 2) crude ACPR = 80% (equivalent to = 20% recurrence). Crude ACPR is defined as the absence of
microscopically determined parasitemia (thick smear), irrespective of axillary temperature, in patients who did not previously meet any
of the criteria of early treatment failure, late clinical failure, or late parasitological failure. Additional aims are to characterize the
antiparasitic activity, safety, tolerability, and pharmacokinetics of SJ733 over the period of 42 days. The results of this trial will help
identify effective, well-tolerated doses for investigation in combination with a partner drug within a Phase 2b clinical study. Study
design table can be found on page 23 of the attached clinical protocol.
The overall study design is to demonstrate proof of concept and serves as an exploratory study. It is not intended to demonstrate
superiority or non-inferiority against a control. Rather, the goal is to establish preliminary data for planning future studies and to assess
whether SJ733 is safe, well tolerated, and the estimated crude ACPR equals or exceeds 80%. As such, there will be no statistical
testing of hypotheses. This exploratory proof of concept study is based on using fixed Day 14 clinical safety and parasitological
response (primary endpoints) to determine dosing regimen and schedules. If patients drop out for reasons unconnected to safety
and efficacy, attempts will be made to replace them to try to ensure the maximum number in each cohort. In total, there will be a
minimum of 20 and a maximum of 60 patients.
Attachments
Attach Type
File Name
StudyDesign
20200406_SJ733_Clinical_Protocol_V1.0_en.docx
StudyDesign
20200430_SJ733_Clinical_Protocol_V1.0_es.docx
StudyDesign
20200430_SJ733_Clinical_Protocol_V1.0_Cert_of_Translation.pdf
Back to Top
Study Population: Describe the characteristics of the subject population, such as anticipated number, age range, gender, ethnic
background and health status. Identify the criteria for inclusion and exclusion. Explain the rationale for the use of special classes such
as fetuses, pregnant women, children, institutionalized, adults with impaired consent capacity, prisoners, economically or educationally
disadvantaged persons or others who are likely to be vulnerable.
If women or minorities are included, please address how the inclusion of women and members of minority groups and their
subpopulations will help you meet your scientific objectives. Exclusion of women or minorities requires clear and compelling rationale
that shows inclusion is inappropriate with respect to the health of the subjects or that inclusion is inappropriate for the purpose of the
study. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. Women of
childbearing potential should not be excluded routinely from participation in clinical research.
Provide the following information:
A description of the subject selection criteria and rationale for selection in terms of the scientific objectives and proposed study
design;
A compelling rationale for proposed exclusion of any sex/gender or racial/ethnic group;
The proposed dates of enrollment (beginning and end);
The proposed sample composition of subjects.
You may reference grant application/sponsor’s relevant protocol pages and attach as an appendix using the below attachment button,
however, a summary paragraph must be provided in the text box below.
Proposed dates of enrollment: November 1st, 2020 to December 31st, 2021
The trial will be conducted in Iquitos, Peru. Patients will be recruited from the community, local health-care clinics, and post-secondary
educational institutions through word-of-mouth, active recruitment by study staff, and self-referral in response to advertisements.
Verbal permission will be sought at private locations where advertisements will be posted, and a signed letter of authorization will be
obtained from any performance site where recruitment activities take place. Men and women between the ages of 18 and 70 years
with P. falciparum or P. vivax malaria monoinfection living in Peru. 2-6 cohorts of adult patients (10 patients per cohort) with acute,
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uncomplicated P. falciparum or P. vivax malaria monoinfection. In total, there will be a minimum of 20 and a maximum of 60 patients.
In general, the people who live in these recruitment areas are representative of the general population that suffers malaria in the
Amazon region. They are generally mestizo and do not live in extreme poverty. Their educational level includes completion of primary
or high school. 
Inclusion Criteria:
1) Male or female, aged 18 to 70 years of age (inclusive) at screening.
2) Body weight between 45 kg and 90 kg inclusive
3) Presence of mono-infection of P. falciparum or P. vivax confirmed by:
a. Fever, as defined by axillary temperature = 37.5°C or oral/rectal/tympanic temperature = 38°C, or history of fever in the previous 24
hours (history of fever must be documented) and,
b. Microscopically confirmed parasite infection: 1,000 to 40,000 asexual parasite count/µL blood
4) Written informed consent provided by participant, in accordance with local practice. If the participant is unable to write, witnessed
consent is permitted according to local ethical considerations.
5) Ability to swallow oral medication.
6) Ability and willingness to participate and to comply with the study requirements
7) Agreement to hospitalization for at least 102 hours and/or until malarial parasites are not detected by microscopy on 2 consecutive
occasions. 
8) Agreement to come back to the hospital on Days 7, 10 or 11, 14, 17 or 18, 21, 24 or 25, 28, 35, and 42.
9) Women of child-bearing potential, has a negative pregnancy test at screening, and agrees to comply with one of the following
during the treatment stage of the study and for a period of 30 days after stopping study drug:
a. Use of oral, implantable, or injectable hormonal contraceptive, either combined or progestogen alone used in conjunction with
barrier method as defined below.
b. Use of an intrauterine device with a documented failure rate of <1% per year.
c. Barrier method consisting of either condom or diaphragm.
d. Male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female.
e. Complete abstinence from intercourse for 2 weeks prior to administration of study drug, throughout the study and for a period of 30
days after stopping study drug.
Exclusion Criteria:
1) Signs and symptoms of severe/complicated malaria according to the World Health Organization Criteria 2010 (Attachment 1:
Definition of Severe Malaria) 
2) Mixed Plasmodium infection.
3) Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study, or severe diarrhea defined as 3 or
more watery stools per day.
4) Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the
NCHS/WHO normalized reference values) 
5) Presence of a significant medical or psychiatric condition, or any other serious or chronic clinical condition requiring hospitalization,
or any other condition that in the opinion of the investigator precludes participation in the study.
6) Female patients must not be either lactating or pregnant as demonstrated by a negative serum point-of-care pregnancy test pre-
dose (the result of the pre-dose assessment must be confirmed negative prior to dosing).
7) Employment under the direct supervision of the investigators or study staff.
8) Clinically significant alterations to hematologic or clinical chemistry parameters that in the opinion of the investigator precludes
participation in the study, including:
a. AST/ALT > 3 x upper limit of normal range (ULN) and total bilirubin is normal
b. AST/ALT > 2 x ULN and total bilirubin is >1 and <1.5 x ULN and conjugated bilirubin is > 35% of the total bilirubin 
c. Total bilirubin > 1.5 x ULN 
d. Serum creatinine levels > 2 x ULN
e. Hb level < 8 g/dL 
f. Platelet level < 50,000/mm3
9) Participation in a clinical study of another investigational small molecule within 30 days or investigational biologic within 90 days
prior to study enrollment or planning to begin such participation during the study.
10) Have received any antimalarial treatment (alone or in combination) in the past containing: 
a. Piperaquine, mefloquine, naphthoquine or sulphadoxine / pyrimethamine within the previous 6 weeks
b. Amodiaquine or chloroquine within the previous 4 weeks
c. Any artemisinin (artesunate, artemether, arteether or dihydroartemisinin) quinine, halofantrine, lumefantrine and any other anti-
malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and 
fluoroquinolones, and azithromycin) within the past 14 days
11) Any medication from a list of prohibited medications as provided in Section 7.6. (page 65 of the Clinical Protocol)
Attachments
Attach Type
File Name
StudyPopulation
20200406_SJ733_Clinical_Protocol_V1.0_en.docx
Subject Recruitment Methods & Privacy: Using active voice, describe plans for the identification and recruitment of subjects,
including how the population will be identified, and how initial contact will be made with potential subjects by those having legitimate
access to the subjects' identity and the subjects' information.
Describe the setting in which an individual will be interacting with an investigator or how and where members of the research team will
meet potential participants. If applicable, describe proposed outreach programs for recruiting women, minorities, or disparate
Section 8 Page 3 of 20
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populations as participants in clinical research. Describe steps taken to minimize undue influence in recruiting potential participants.
Please note: Based upon both legal and ethical concerns, the UK IRB does not approve finder’s fees or “cold call” procedures made
by research staff unknown to the potential participant. The ORI/IRB does not control permission to any UK listserv, mass mailing list,
etc. Investigators must secure prior approval for access and use from owners/managers.
For additional details, see topic "Recruitment of Subjects/Advertising" on ORI's IRB Survival Handbook web page and the PI Guide to
Identification and Recruitment of Human Subjects for Research [PDF].
Patients will be recruited from the community, local health-care clinics, and post-secondary educational institutions through word-of-
mouth, active recruitment by study staff, and self-referral in response to advertisements. Verbal permission will be sought at private
locations where advertisements will be posted, and a signed letter of authorization will be obtained from any performance site where
recruitment activities take place. All recruitment materials will be approved by the EC before use. Advertisements will indicate the
nature of the study and provide a phone number for further information. Currently, the recruitment sites include 14 villages that have
health posts in the districts of Iquitos, San Juan Bautista, and Punchana. Some are located along the road and others at the edges of
the rivers. The distance by land or river to the city of Iquitos is less than 1.5 hours, most less than 1 hour. 
In each health post there are health personnel, including a laboratory technician, who will make the initial diagnosis of parasitemia
(thick smear). The rate of mixed infections varies between 4% and 6% when thick smear is used as a diagnostic method. When a
Patient tests positive for P. vivax malaria or P. falciparum monoinfection, the health personnel will call the study field coordinator by
telephone, who can then send a field worker to verify the Patient's willingness to participate in the study. Study investigators or their
designees will explain the study to potential research patients including the inclusion and exclusion criteria. Persons who indicate they
are interested in participating in the study and are potentially eligible will be offered transport to a screening visit. During the screening
visit, study investigators or their designees will assign a participant ID and provide the individuals with information about the study and
an opportunity to ask questions. If the individual is willing, written informed consent for study participation will be obtained.
Back to Top
Advertising: Specify if any advertising will be performed. If yes, please see “IRB Application Instructions - Advertisements” for
instructions on attaching copies of the information to be used in flyers or advertisements. Advertisements must be reviewed and
approved by the IRB prior to use. For additional details, see topic "Recruitment of Subjects/Advertising" on ORI's IRB Survival
Handbook web page for the PI Guide to Identification and Recruitment of Human Subjects for Research [D7.0000] document [PDF].
If you will be recruiting subjects via advertising at non-UK owned or operated sites, you should include a copy of written permission
from that site to place the advertisement in their facilities.
Note: Print and media advertisements that will be presented to the public also require review by UK Public Relations (PR) to ensure
compliance with UK graphic standards, and equal opportunity language. See Advertising Instructions for PR contacts. 
Please find a copy of the advertisements attached. 
The Patient Brochure has been designed in close collaboration with the local Peruvian research team to ensure it is consistent with
local expectations and regulations. The Patient Brochure has also been reviewed and approved by UKPR and Communications
Director at University of Kentucky Center for Clinical & Translational Science Mallory Powell. Email: mallory.powell@uky.edu Phone:
615.828.0000
Attachments
Attach Type
File Name
Advertising
20200501_Patient_Brochure_Cert_of_Translation.pdf
Advertising
20200615_Patient_Borchure_ES_EN_v2.pdf
Advertising
20200615_Patient_Borchure_ES_EN_v2_PRSTAMPED.pdf
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Informed Consent Process: Using active voice, describe the consent/assent procedures to be followed, the circumstances under
which consent will be sought and obtained, the timing of obtaining informed consent, whether there is any waiting period between
informing the prospective subject and obtaining consent, who will seek consent., steps taken to minimize the possibility of coercion or
undue influence, the method used for documenting consent, and if applicable who is authorized to provide permission or consent on
behalf of the subject. Note: all individuals authorized to obtain informed consent should be designated as such in the E-IRB "Study
Personnel" section of this application.
Describe provisions for obtaining consent/assent among any relevant special populations such as children (see Children in Research
Policy [PDF] for guidance), prisoners (see Summary of Prisoner Regulations [PDF] for guidance), and persons with impaired
decisional capacity (see Impaired Consent Capacity Policy [PDF] for guidance). Describe, if applicable, use of specific instruments or
techniques to assess and confirm potential subjects’ understanding of the nature of the elements of informed consent and/or a
description of other written materials that will be provided to participants or legally authorized representatives. If you have a script,
please prepare it using the informed consent template as a guide, and submit it on a separate page.
Informed Consent for Research Involving Emancipated Individuals
If you plan to enroll some or all prospective subjects as emancipated, consult with UK legal counsel when preparing the IRB
application and prior to submitting the application to the IRB. Include legal counsel’s recommendations (legal counsel’s
recommendations may be attached in the E-IRB "Additional Information" section as a separate document, if necessary). For a
complete definition of emancipated minors, see the section on Emancipated Individuals in the Informed Consent SOP [PDF].
Informed Consent for Research Involving Non-English Speaking Subjects
If you are recruiting non-English speaking subjects, the method by which consent is obtained should be in language in which the
subject is proficient. Describe the process for obtaining informed consent from prospective subjects in their respective language (or
the legally authorized representative’s respective language). In order to ensure that individuals are appropriately informed about the
study when English is their second-language, describe a plan for evaluating the level of English comprehension, and the threshold for
providing a translation, or explain why an evaluation would not be necessary. For additional information on inclusion of non-English
speaking subjects, or subjects from a foreign culture, see IRB Application Instructions for Recruiting Non-English Speaking
Participants or Participants from a Foreign Culture.
Research Repositories
If the purpose of this submission is to establish a research repository describe the informed consent process. For guidance regarding
consent issues, process approaches, and sample language see the Sample Repository/Registry/Bank Consent Template [PDF]
Patients will be recruited from the community, local health-care clinics, and post-secondary educational institutions through word-of-
mouth, active recruitment by study staff, and self-referral in response to advertisements. Verbal permission will be sought at private
locations where advertisements will be posted, and a signed letter of authorization will be obtained from any performance site where
recruitment activities take place. In each health post there are health personnel, including a laboratory technician, who will make the
initial diagnosis of parasitemia (thick smear). When a Patient tests positive for P. vivax malaria or P. falciparum monoinfection, the
health personnel will call the study field coordinator by telephone, who can then send a field worker to verify the Patient's willingness
to participate in the study. Study investigators or their designees will explain the study to potential research patients including the
inclusion and exclusion criteria. Persons who indicate they are interested in participating in the study and are potentially eligible will be
offered transport to a screening visit. During the screening visit, study investigators or their designees will assign a participant ID and
provide the individuals with information about the study and an opportunity to ask questions. If the individual is willing, written informed
consent for study participation will be obtained.
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Research Procedures: Describe the research procedures that will be followed. Identify all procedures that will be carried out with
each group of subjects. Differentiate between procedures that involve standard/routine clinical care and those that will be performed
specifically for this research project.
STUDY SPECIFIC PROCEDURES 
1) Inclusion/exclusion criteria; Relevant medical history/Current medical conditions
2) Demography
3) Increased number of Physical examinations (body height, body weight, body temperature, blood pressure, pulse rate,)
4) Alcohol, drug and smoking history 
5) Pregnancy test at completion or withdrawal 
6) Meal record within 3 hours prior to the dose of study medication
7) Investigation New Drug administration (all cohorts will receive SJ733; cohorts 1 and 3 will also receive Cobicistat)
8) Study Completion information
9) ECG evaluation
10) Hematology; Blood chemistry; Urinalysis
11) Adverse Events tracking
12) Concomitant medication/ Significant non-drug therapies
13) Pharmacokinetic (PK) blood collection
14) Increased number of Parasitemia blood collection and assessment (microscopy/qPCR) 
15) Parasite genetic assessments (to determine potential mechanisms of resistance) 
STANDARD/ROUTINE CLINICAL CARE PROCEDURES
1) Single Physical examinations (body height, body weight, body temperature, blood pressure, pulse rate,)
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2) Single Pregnancy test
3) Concomitant medication/ Significant non-drug therapies
4) diagnostic Parasitemia determinations (microscopy/qPCR) 
5) Administration of local standard drug therapy
Attachments
Attach Type
File Name
ResearchProcedures
20200406_SJ733_Clinical_Protocol_V1.0_en.docx
Data Collection: List the data or attach a list of the data to be collected about or from each subject (e.g. interview script, survey tool,
data collection form for existing data).
If the research includes survey or interview procedures, the questionnaire, interview questions or assessment scales should be
included in the application (use attachment button below).
The data collection instrument(s) can be submitted with your application in draft form with the understanding that the final copy will be
submitted to the IRB for approval prior to use (submit final version to the IRB for review as a modification request if initial IRB approval
was issued while the data collection instrument was in draft form).
Note: The IRB approval process does not include a statistical review. Investigators are strongly encouraged to develop data
management and analysis plans in consult with a statistician.
Details regarding the data to be collected throughout the trial from screening to finalization can be found on pages 61 - 65 of the
attached Clinical Protocol and include:
• Written informed consent
• Demographic data
• Medical and surgical history and details of current medical conditions
• Social history (including previous and current use of alcohol, tobacco products and drugs of abuse)
• Previous and concomitant medications (medications used currently and in the 28 days prior to screening will be recorded in the
patient’s CRF)
• Use of herbal products
• Signs and symptoms of malaria
• Height and body weight
• A complete physical examination (excluding genitourinary unless indicated)
• Vital signs (blood pressure, pulse rate and axillary body temperature) after the patient has been resting in the supine position for 5
minutes
• Standard 12-lead ECG (single recording)
• Blood sampling for the following:
- determination of plasma drug concentrations (SJ773 and its primary metabolite SJ506)
- microscopy (thick and thin slides) for parasite counts and parasite species identification
- qPCR determined parasitemia
- hematology and chemistry safety laboratory tests, including methemoglobin
• Point-of-care whole blood/serum pregnancy test (females only)
• Review of eligibility criteria (including review of essential safety laboratory results).
• Monitoring and recording of AEs and SAEs
- G6PD enzyme test (P. vivax Patients only)
Attachments
Attach Type
File Name
DataCollection
20200406_SJ733_Clinical_Protocol_V1.0_en.docx
Resources: Describe what resources/facilities are available to perform the research (i.e., staff, space, equipment). Such resources
may include a) staffing and personnel, in terms of availability, number, expertise, and experience; b) psychological, social, or medical
services, including counseling or social support services that may be required because of research participation; c) psychological,
social, or medical monitoring, ancillary care, equipment needed to protect subjects; d) resources for subject communication, such as
language translation services, and e) computer or other technological resources, mobile or otherwise, required or created during the
conduct of the research. Please note: Some mobile apps may be considered mobile medical devices under FDA regulations (see
FDA Guidance). Proximity or availability of other resources should also be taken into consideration, for example, the proximity of an
emergency facility for care of subject injury, or availability of psychological support after participation. 
Research activities conducted at performance sites that are not owned or operated by the University of Kentucky, at sites that are
geographically separate from UK, or at sites that do not fall under the UK IRB’s authority, are subject to special procedures for
coordination of research review. Additional information is required (see IRB Application Instructions - Off-Site Research web page);
supportive documentation can be attached in the E-IRB "Additional Information" section. Provide a written description of the role of the
non-UK site(s) or non-UK personnel who will be participating in your research. The other site may need to complete its own IRB review,
or a cooperative review arrangement may need to be established. Contact the Office of Research Integrity at (859) 257-9428 if you
have questions about the participation of non-UK sites/personnel.
Section 8 Page 6 of 20
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If the University of Kentucky is the lead site in a multi-site study, or the UK investigator is the lead investigator, describe the plan for
managing the reporting of unanticipated problems, noncompliance and submission of protocol modifications and interim results from
the non-UK sites.
PI: Professor Alejandro Llanos Cuentas, MD, PhD.
Site name: Asociacion Civil Selva Amazonica (ACSA), Iquitos, Loreto-Peru.
Clinic is managed by Dr. Martin Casapia Morales MD 
Alejandro Llanos Cuentas, Clinical lead. Dr. Llanos Cuentas has more than 30 years of experience in planning, direction, execution,
monitoring and evaluation of clinical trials, research and interventions for the prevention and control of leishmaniasis and malaria. Dr.
Llanos Cuentas is a founder and head of the Unit of Leishmania and Malaria, Instituto de Medicina Tropical "Alexander von
Humboldt", Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru and also serves as the president of a group of experts
working on Malaria Elimination in partnership with the Peruvian Ministry of Health (MoH). Dr. Llanos Cuentas routinely serves on Data
Safety Monitoring Boards for the NIH-USA and has been the Principal Investigator or Co-Investigator in more than 50 studies (30
clinical trials), including playing a pivotal role in several recent Phase 2 and 3 trials of antimalarials including tafenoquine and DSM265
The Asociacion Civil Selva Amazonica (ACSA) has been involved in conducting research with outstanding performance and
community-wide acceptance since 2002, the site has been devoted to clinical research in the field of HIV, tuberculosis (TB), dengue,
zika and malaria. ACSA has been established by DAIDS as a clinical research site for the HIV Vaccine Trials Network (HVTN) and the
HIV Prevention Trials Network (HPTN), as result of this the site has big experience conducting clinical trials in high risk population
(MSM) participants for different studies sponsored by the NIAID/NIH such as HPTN 039 where 200 HIV-negative, HSV-2 men who
have sex with men (MSM) were enrolled, with a HIV incidence of 3.9 per 100 person-year and an incidence of HSV-2 positive genital
ulcers by 63% , the site has also performed non-vaccines HIV prevention trials such as “Chemoprophylaxis for HIV Prevention in
Men” (iPrEx) study, where it was the second largest enrolling site with 460 enrolled participants, the cohort participants from these
studies are at increased risk for STIs, with consistently high incidences of Neisseria gonorrhea and Chlamydia trachomatis1,2,3,4.
The site has also expertise enrolling general population for vaccines studies sponsored by the NIAD/NIH5, the site has currently
ongoing a candidate Zika vaccine study sponsored by NIAID where 651 participants were enrolled (general healthy population).
Recruitment and retention for all studies are achieved through community outreach including peer leaders and informational meetings
in bars, nightclubs, and brothels for high risk population and at universities, institutes and neighborhoods for general population.
ACSA has been recognized by DAIDS Networks for its outstanding achievements in enrollment, retention rates, and data quality. We
have also performed observational studies sponsored by NIH were pregnant women and scholar children have been enrolled for
studies related to parasitic infections. 
Organizational Structure of the Clinical Site
ACSA is led by the Dr Casapia, who receive support functions from four different areas conformed by the IoRs, CRS Coordinator,
Study Coordinators and Logistics. This organizational structure is flexible responsive and adaptable allowing for a cohesive and
integrated approach to support the scientific priorities of the research networks. The ability to adapt hinges on having clear lines of
authority, organizational components focused on providing centralized, common and standardized services, and organizational
components that are focused on the particular needs of specific research projects. This structure is simple but capable of handling
highly complex clinical trials, and also capable of responding to rapidly changing network and pharmaceutical industry needs. Clear
lines of authority and communication channels reflect such a conceptual framework. The ACSA CRS Leader represented by Dr
Casapia and CRS Coordinator provide the overall leadership to ensure cohesive and coordinated functioning of all CRS components
in their interaction with the supporting areas. Each network trial is led by an Investigator of Record (IoR) and a Study Coordinator who
knows every detail of the study and interacts with the CRS Coordinator and CRS Leader in order to achieve study goals. Alternatively,
an experienced Community Advisory Board (CAB) guarantees community engagement in research development and implementation
The site includes Administrative, Clinic, Laboratory, Pharmacy, Data and Community Education areas, each led by an experienced
Head of area. Dr Casapia is in daily communication with the Heads of each area by email, telephone, and in-person meetings. In
addition, Dr Casapia and all the Heads of area meet at least twice a month to discuss all ongoing studies. The Heads of each area
lead the staff in their respective sections, performing monthly meetings. The Clinic Section Head also oversees the Data Manager
and the Pharmacist. 
The ACSA site is currently housed in five buildings occupying a total area of 22,556 ft2, located 8 blocks from the main square. Their
facilities include clinical, research, pharmacy, laboratory, data management, IT, and administration areas. The Clinical area is located
in the first floors and has a total area of 8,544ft2, it has rooms for hospilization and an Emergency room. In the first floor we also have
vaccination and infusion rooms used according protocol requirements in research. The research area is located in the second
(6567ft2), third floor (2487ft2), four (2475ft2) and five floor (2475ft2). The second and third floor have 12 rooms used for counseling,
informed consent process and medical examination, 2 waiting rooms, a pharmacy, two specimen collection rooms and vaccination
rooms. The layout of the rooms is designed to provide comfort and confidentiality for participants from the different clinical trials. All
the rooms used by participants are equipped with computers for the completion of self-administered questionnaires or any other kind
of questionnaires according protocol requirements. In the third floor we also have a room designated to receive monitoring, audit or
inspection visits from any local or international regulatory entity. The fourth floor has administrative areas, the office of the Principal
investigator, the CRS coordinator and study coordinator are located in this floor. The fifth floor has the Data Management office and a
room used for staff training. 
ACSA provides the community with medical services in multiple specialty areas, outpatient services, hospitalization, surgery, 24-hour
emergency, and diagnostic support. This area is comprised of 2 waiting rooms, a pharmacy, medical triage, 6 medical examination
rooms, specimen collection room, surgery and recovery room. Within diagnostic support, ACSA provides X-Ray, mammography,
ultrasound and EKG. There is also a shock trauma area, topical emergency and administrative offices. 
Section 8 Page 7 of 20
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Laboratory: 
The ACSA laboratory is located on the second floor and has a total area of 4400 ft2. This area houses 2 areas of PBMC,
biochemistry (clinical and research), hematology (clinical and research), immunology, microbiology, sample preparation, storage and
laboratory management. The ACSA laboratory complies with international quality control standards and is currently certified by the
College of American Pathologists and the UK-NEQAS, Digital PT Oneworld, IQA of DUKE University, who provide external quality
control for evidence of competence. The laboratory infrastructure includes fully automated and semiautomatic equipment approved
by the FDA of the United States. The entire team has regularly scheduled preventive maintenance.
The ACSA laboratory has a panel of more than 150 diagnostic tests. They include hematology (complete blood count, hemoglobin,
ESR, hematocrit, platelet count, corpuscular constants, WBC, direct and indirect Coombs tests, TP, TPT, CD4 / CD8 counts, cell
isolation and cryopreservation); Biochemistry (liver, lipids, thyroid and pregnant profile, glucose, urea, creatinine, arterial blood gases,
troponin I); Immunology (rapid HIV tests, syphilis, C-reactive protein, ASO, latex, hCG, viral hepatitis B ELISA, viral hepatitis C,
confirmatory HIV immunoblot test and tumor markers); Bacteriology (culture and sensitivity for urine, blood and bone marrow);
Mycology (cultivation and isolation of fungi); and Parasitology (direct examination, concentration methods, stool culture and isolation).
In addition, the ACSA Laboratory has agreed with an external laboratory for backup tests, IMPACTA Barraco Laboratory, Anglolab
laboratory.
Pharmacy: 
The ACSA Research Pharmacy is located on the second floor of the research clinic. There are 4 areas in total that are divided into: 2
storage areas, 1 preparation area for intravenous infusions and 1 area for pharmacy management. The pharmacy has 10.76 ft2 of
total area with restricted access for all storage areas of study products, preparation of infusions and pharmacy files (insured by
alarms and electric locks). The main door has an electric lock whose access is exclusive only to the Pharmaceuticals.
In the Management area, the administrative pharmacy tasks are performed, in this area there are cabinets with double keys for the
documentation of the different protocols, Internet access, fax equipment, photocopier, telephone, computer equipment for every
pharmacist also there is an air conditioning
The storage area is divided in two, one destined to store the products that need refrigeration or lower temperatures and the other
area is for the products that are stored at room temperature. The room and equipments temperature are monitored 24 hours a day,
365 days a year through a system of automatic monitoring called Sensaphone. Additionally, all freezers and refrigerators are
equipped with a continuous temperature monitoring and recording system that records the temperature in a circular format. This
record is changed every week and stored in a closed cabinet. The equipment includes hygrometers and memory thermometers that
measure the minimum and maximum temperature as backup monitoring. 
The Infusion Preparation Area has a Biosafety Cabin, air filter system. (HEPA) This area has the accreditation of Microbiological
Control (annual) and Particle Count (semi-annual)
Data:
The ACSA Data Management Area (AMDA) has the function of ensuring the quality of clinical research data, which are expressed in
the functions of its members. Currently this area works with a data management scheme regulated by a Plan called Clinical Quality
Management Plan (CQMP) and by the standard procedures called SOP of data management. The characteristic regulations of each
protocol, of each network, are explained in the data management plans for the specific protocol.
ACSA data management Head of area has 15 years of experience performing QC/QA activities in different clinical trials obtaining a
good data performance record. A Clinical Quality Management Plan is in place that governs the QC/QA activities. 
The data management area has an appropriate infrastructure to maintain study documentation in optimal conditions and assure
confidentiality. The data management area has a file area where is the documentation of protocols that were already closed is located
on the third floor and the office area together with the documentation file of the active protocols located on the fifth floor. Access is
restricted to data managers only. This office is fully equipped with a Multi-functional Printer, computers and air conditioner.
Currently this area has 23 highly trained professionals among data managers and data entries to perform Quality Assurance (QA) and
Quality Control (QC) activities for the different research protocols. They are divided into three teams, each one for a defined protocol
and all of them led by a protocol head.
Staffing Plans: 
ACSA clinical area has a staff of physicians that offer care for cardiology, pulmonology, pediatrics, surgery, internal medicine,
infectious diseases, neurology, and dermatology. The ACSA clinical research area has a staff of 20 physicians, 7 of them specialist in
infectious diseases. The staff is also comprised of 10 nurses, 4 pharmacists, 6 medical technologists and 8 lab technicians. 
Compliance Procedures and Capabilities of Clinical Site Related to IND Submissions: 
The daily clinical research operations in the ACSA site are in full compliance with Good Clinical Practices (GCP), Good Clinical
Laboratory Practices (GCLP), Human Subjects Protection (HSP), and U.S. FDA, NIAID and Peruvian regulations. Standard Operating
Procedures, Pharmacy Establishment Plans, Quality Management Plans and an Evaluation Plan have been implemented, following
DAIDS guidelines. The CRS Coordinator is responsible for overseeing, following and enforcing institutional, sponsor, local and
federal regulatory policies. The CRS Coordinator is also responsible for delivering high-level quality data as well as secure and
confidential study documents in compliance with Quality Standards from the DAIDS scientific research networks. Additionally, the
ACSA Laboratory Director is responsible for performing assays under Good Clinical Laboratory Practices (GCLP). All research staff
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are trained and certified in Research with Human Subjects and GCP, including refresher training every two years. Research at the site
must be approved by an IRBs as a general rule. Standard operating procedures (SOPs) in place for all research activities are
reviewed and updated as needed. Assessment of patient safety, treatments, and outcomes is performed by the study clinicians,
overseen by Dr Casapia. Reporting of adverse events follows the guidelines of both IRBs; additional reporting to sponsors (e.g.
DAERS) is performed for specific studies. 
Data management is handled by a Data Manager overseen by the Head of area. For studies with onsite data entry, hard copies of the
case report forms (CRFs) are reviewed at the end of each day by the Study Clinician. A second review is performed by the Data
Manager, and data are entered in a secure, password-protected database. 
Data and sample collection: 
Collection of questionnaire data is performed by study clinicians, nurses, and counselors. Data management procedures are detailed
above. Collection, labeling, storage, tracking, and transfer of samples are performed according to SOPs at the site. Briefly, samples
are labeled by lab trained staff at the time of collection and in some cases by the study nurse; a log of collected samples is created
simultaneously. The samples and log are processed or transferred according study requirements. Samples for storage or other tests
(e.g. PBMC separation, nucleic acid amplification) are shipped and sent to the corresponding laboratory for processing. Lab staff has
a big expertise in sending samples locally or internationally, most of lab staff has IATA training. When the samples are processed on
site, there is a staff that receives the sample and verifies the samples and the documents received with it. Samples for
cryopreservation are barcode labelled and entered into a Freezerworks sample tracking, biorepository, and freezer inventory program
(LDMS). Shipments are prepared with a shipping manifest and transported internationally according to IATA regulations. Depending
on required shipping conditions, samples are shipped at ambient temperature or on dry ice, using a commercial vendor (World
Courier). These procedures have been highly successful for >15 years of research at the clinical site, and will be used to support
VTEU studies.
Potential Risks: Describe any potential risks or likely adverse effects of the drugs, biologics, devices or procedures subjects may
encounter while in the study. Please describe any physical, psychological, social, legal or other risks and assess their likelihood and
seriousness.
SJ733 is a new investigational drug that has not yet been approved by the US Food and Drug Administration (FDA) or any other
regulatory authority for commercial use. Therefore, there may be risks associated with SJ733 that are not foreseen, known, or
understood at this time.
SJ733 has been well tolerated in clinical studies with 51 human volunteers including those experimental infected with malaria (P.
falciparum). During the Phase 1a trial, all subjects tolerated the study drug well with no serious adverse events or dose limiting
toxicities noted following receipt of the drug. Two adverse events (AEs) were judged to be possibly related to SJ733: 1) grade 1 low
leukocyte count first noted on day 7 post dose in a clinically asymptomatic participant; 2) grade 2 proteinuria (2+ urine protein noted
on urinalysis) at 24 h post dose in an otherwise asymptomatic participant with urine specific gravity of 1.023 (range 1.020–1.025) that
was judged to be not clinically significant (trace proteinuria on days 2 and 7 post-dose, resolved by day 14 post dose). No Grade 3 or
Grade 4 AEs were noted. There were no clinically significant ECG or methemoglobin formation findings. 
During the Phase 1b the only SJ733-related adverse event observed was mild bilateral foot paraesthesia (Grade 1) seen in a single
patient in the 150 mg cohort that lasted 3·75 h and resolved spontaneously. Transient asymptomatic inoculum-related clinical and
laboratory adverse effects were observed in the 150 mg cohort but not with the higher dose of 600 mg. Laboratory changes
observed in the first cohort included significant elevations in ALT in 3 subjects (> 5x ULN) where early and rapid recrudescence
occurred. Clinical and laboratory adverse events were less common in cohort 2 (600 mg of SJ733), with only 1 subject experiencing
ALT > 3x ULN. These transient and isolated ALT/AST elevations with no change in bilirubin have been observed in other malaria
challenge studies including studies using registered antimalarials and are believed to be inoculum-related. No subjects had out of
normal range methemoglobin values. 
In studies in dogs, SJ733, at dose exposure levels much higher than what are expected in this study, caused reversible (temporary)
methemoglobinemia after a single dose. Methemoglobinemia is a blood disorder in which an abnormal amount of methemoglobin, a
form of hemoglobin, is produced. Hemoglobin is the protein in red blood cells that carries and distributes oxygen to the body. With
methemoglobinemia, the hemoglobin can carry oxygen but is unable to release it so the body can use it. Early symptoms of
methemoglobinemia include pale, gray or blue colored skin, lips, and nail beds, lightheadedness, headache, tachycardia (rapid heart
rate), fatigue, shortness of breath, and lethargy. These symptoms in otherwise healthy people with methemoglobinemia are seen
when methemoglobin levels are 20-30%. As part of this study patient methemoglobin levels will be closely followed before and after
administration of SJ733.
Cobicistat (Tybost®) is a potent CYP3A4 inhibitor used as "pharmacoenhancer" for boosting exposures to CYP3A4 substrates and
more particularly human immunodeficiency virus (HIV) drugs. Cobicistat was shown to be well tolerated in healthy subjects after both
single dose (50-400 mg) and multiple dose (50-300 mg for 14 days) administration. After single dose administration all the AEs
observed were of Grade 1. The most frequently reported AEs (in only 2 subjects) were headache, somnolence, and abnormal
dreams. No notable changes in biology parameters, vital signs or ECGs (QTc) were detected in the first-in-man study. In subsequent
studies with multiple dose administration of cobicistat, it was shown that the drug increases serum creatinine concentration by
decreasing its elimination, resulting in a decrease in estimated glomerular filtration rate (eGFR). The rise in serum creatinine
concentration and decline in eGFR was reversible within 7 days after the discontinuation of cobicistat. Cobicistat is approved in the
USA. This study will use 3-consecutive daily doses of 150 mg of cobicistat. No significant changes have been observed in blood,
hepatic, renal, or cardiac function attributable to SJ733 in people that have taken SJ733 or SJ733 in combination with cobicistat
As with all new drugs and combinations, unexpected and unforeseen adverse events can result. If the proposed therapy is ineffective
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or not tolerated, patients will receive standard treatment from the study physicians following the protocol for treating malaria according
to current Peruvians standards (see Available Alternative Treatment).
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Safety Precautions: Describe the procedures for protecting against or minimizing any potential risks, including risks of breach of
confidentiality or invasion of privacy. Where appropriate, discuss provisions for ensuring necessary medical or professional
intervention in the event of adverse events, or unanticipated problems involving subjects. Also, where appropriate, describe the
provisions for monitoring the data collected to ensure the safety of subjects. If vulnerable populations other than adults with impaired
consent capacity are to be recruited, describe additional safeguards for protecting the subjects’ rights and welfare.
Established antimalarial therapy will be given if a patient meets any of the following criteria:
1) Clinical decline or lack of clinical improvement or decrease in platelets by > 20% for Patients with a platelet count at inclusion of
between 50,000/mm3 and 74,999/mm3 (thrombocytopenia grade 2) or a drop in platelet count to < 50,000/mm3 for 
Patients with a platelet count of > 75,000/mm3 at inclusion, at 24 hours for P. vivax malaria and 12 hours for P. falciparum malaria
Patients with a = 25% increase in parasitemia in comparison to baseline with or without fever.
2) Development of any clinical complications (WHO definition of complicated/severe malaria, WHO [2013])
3) Parasitemia > 100,000/µL for P. falciparum at any time with or without fever
4) Parasitemia > baseline (from the slides taken 30 min before start of treatment) with or without fever, 48 hours after first dose for P.
vivax and 36 hours after first dose for P. falciparum
5) Failure to clear all parasites by microscopy associated with axillary fever > 37.5°C between 72 hours and 7 days for P. vivax and 60
hours and 5 days for P. falciparum
6) Failure to clear all P. vivax parasites by microscopy with or without fever on Day 7 and P. falciparum parasites by microscopy with or
without fever on Day 5
7) Patient exhibits a rise of microscopically detectable parasitemia between Day 7 and Day 42 with or without fever
Following discharge, the patient will be monitored as an out-patient every 3-4 days: (on Days 7, 10 or 11, 14, 17 or 18, 21, 24 or 25,
28, and 35) until the final clinic visit on Day 42. At each visit the patient will be accompanied by the health care professional to Clínica
de la Asociación Civil Selva Amazónica (ACSA) in Iquitos for the following examinations:
• Physical examinations and body temperature measurements will be conducted at every visit (Days 7, 10 or 11, 14, 17 or 18, 21, 24
or 25, 28, 35, 42).
• Blood samples will be taken for parasitology (microscopy and qPCR) at every visit (Days 7, 10 or 11, 14, 17 or 18, 21, 24 or 25, 28,
35, and 42).
• Additional blood samples for hematology and clinical chemistry assessments will be taken on Days 7, 14, 28, 35, and 42.
After discharge (negative microscopy), and during the 42 day follow up period, if a study subject displays parasitological signs (as
confirmed by positive microscopy) or develops clinical signs of malaria, he/she will be given standard of care according to the
national treatment guidelines and supervised by the investigator.
Patient data will be logged into an Electronic Data Capture system at site by the site. Where the data violate validation checks queries
will fire within the system for the Investigator to address and respond. Medications will be coded using the WHO-drug dictionary.
Medical conditions and AEs will be coded using the latest version of the MedDRA dictionary.
When data entry has been completed and all outstanding queries have been resolved for a CRF, the CRF will be eligible for QC
checking. A sample of 9 (i.e. ?n + 1) Patients will be selected for QC checks and 100% of these Patients’ data will be audited. In
addition, 100% of demography, parasite count, AEs and withdrawal data will be checked for all Patients. The highest acceptable error
rate for QC is 0.5%. A higher error rate will prompt a review of a further sample of 9 Patients. If the error rate remains above 0.5%, a
100% QC check of all data will be conducted. 
All errors discovered will be corrected on the database and the corrections will be audit-trailed and will undergo a QC check. On
satisfactory completion of the QC checks, the database will be locked.
Analytic data management will be performed by faculty and staff at the University of Kentucky. Methods for data transfer will involve a
secure platform (e.g. REDCap SendIt! Feature). Data transfer protocols from independent CRO to UK faculty and staff data
management team will be described in the data management plan (DMP). 
Analytic data management will utilize Research Electronic Data Capture (REDCap) as an electronic data management system.
REDCap is a software toolset and workflow methodology to manage research data for research studies. The consortium, initiated in
August 2006, has shared the software and methodology with the larger research community of CTSA-, GCRC- and RCMI-
participating institutions. The consortium is open to any academic institution, and members are provided with software and support at
no charge, with the expectation that participants will contribute back to the overall project. 
Limited study personnel will have administrative rights to make changes to the data, and all changes will be tracked through the
REDCap audit trail. The data entered into the REDCap database is stored on servers in the UK Research Data Management Center
and is backed-up on a regular basis. All raw datasets exported from REDCap as well as all analysis datasets are stored on
UKHealthcare servers behind the medical center firewall. Access will be limited to study personnel involved with data management
and data analysis.
SAS v9.4 or higher will be used to create and integrate any resulting datasets. SAS analysis datasets will be created, and SAS
programs will be developed to further investigate potential data issues via simple descriptive statistics and plots. Summary reports
will be provided periodically during the course of the project to verify accuracy of data entry and provide early opportunities for
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clarification of questions and correction of errors and omissions. For analysis datasets, Data Definition Tables (DDTs) are included to
document all variables (both raw and derived) included in the analysis datasets. This includes the variable name, label, type, length,
format, coded values and logic for creating derived variables. All derived variables are independently programmed by two SAS
programmers and then compared using SAS PROC COMPARE. All differences are documented and changes are made to the SAS
code as necessary until the PROC COMPARE output is clean, i.e. showing no differences. For raw data, a data dictionary is available
through REDCap. The data dictionary provides a description of all data fields including the field name, label, field type, response
option coding and branching logic. 
Project data will include raw survey data stored in REDCap and analysis. All project data will be maintained on UK Healthcare servers
as described in the following section.
EDT Security: The EDT maintains a 900 square feet data center with independent power, cooling, and humidity control on the UK
campus. The entire workspace is secured by electronic access with logged entry and exit to all facility offices and monitored with a
security camera. The internal communication network is protected by multiple firewalls. All data on servers are sent to off-site backup
each day. The network is managed by a full-time staff to support file servers, virtual machines, and the physical network. EDT
undergoes periodic comprehensive audits in addition to a security risk assessment through UK HealthCare IT Security that is
delivered bi-weekly. This includes a thorough review of Privacy and Confidentiality policies and procedures in addition to hardware
security. The objective of the security risk assessment is to identify opportunities for improvement, prioritize any needed remediation
activities, scope, and plan and remediate any found deficiencies. All source data, clinical records and laboratory data relating to the
study will be retained in the archive for a minimum of 15 years after the completion of the study. Written agreement from the Sponsor
must precede destruction of the same.
Benefit vs. Risk: Describe potential benefits to the subject(s); include potential benefits to society and/or general knowledge to be
gained. Describe why the risks to subjects are reasonable in relation to the anticipated benefit(s) to subjects and in relation to the
importance of the knowledge that may reasonably be expected to result. If you are using vulnerable subjects (e.g., impaired consent
capacity, pregnant women, etc…), justify their inclusion by describing the potential benefits of the research in comparison to the
subjects’ vulnerability and the risks to them.  For information about inclusion of certain vulnerable populations, see the IRB/ORI
Standard Operating Procedure for Protection of Vulnerable Subjects [C3.0100] [PDF].
Malaria is a devastating disease inflicting high social and economic impact worldwide. To combat increasing levels of drug resistance,
the WHO recommends combinations of artemisinin derivatives, the most potent and rapidly acting anti-malarial agents available, with
long-acting antimalarials (ACT) for the treatment of uncomplicated P. falciparum malaria (e.g. Coartem® (artemether-lumefantrine),
Eurartesim® (dihydroartemisinin-piperaquine), artesunate-mefloquine, etc.). Mutations continue to emerge that mediate resistance to
artemisinin, delay parasite clearance upon artemisinin treatment, and may ultimately lead to treatment failures, suggesting artemisinin
resistance is rapidly becoming a global issue. In addition, emerging cases of resistance to piperaquine in combination with
dihydroartemisinin in Cambodia (unpublished results) as well as undesired side effects of mefloquine underline the need for
development of a novel, safe, rapidly acting antimalarials, not subject to current resistance mechanism. 
The clinical candidate SJ733 is an orally bioavailable, rapidly acting compound that targets PfATP4, a mechanism for which there is
currently no resistance in the field. SJ733 is active against all drug-resistant malaria strains tested. It acts against both the blood and
sexual stages of the parasite life cycle and is active against both Plasmodium falciparum and Plasmodium vivax. No significant
toxicological responses have been seen in humans to date that can be attributed to SJ733 administration. SJ733 has been
demonstrated to block the proliferation of the parasite causing malaria in human subjects. Overall, SJ733’s excellent tolerability and
safety profile, combined with its rapid antiparasitic effect and reduced susceptibility to resistance, support its candidacy as an
antimalarial therapy and suggest it may afford a viable replacement for artemisinin in current treatment therapies.
The results of this study will help to find new treatments for malaria. The results of the study will help to see if SJ733 with or without
cobicistat can be a new treatment for malaria. If SJ733 with or without cobicistat is shown to be safe and effective for the treatment of
malaria, it may help other patients with malaria that cannot be cured with the currently available drugs.
SJ733 is a new investigational drug that has not yet been approved by the US Food and Drug Administration (FDA) or any other
regulatory authority for commercial use. Therefore, there may be risks associated with SJ733 with or without combination with
Cobicistat that are not foreseen, known, or understood at this time. If the proposed therapy is ineffective or not tolerated, patients will
receive standard treatment from the study physicians following the standard protocol for treating malaria according to current
Peruvians standards. A review of each study cohort will be conducted by the safety review team and the data and safety monitoring
board and a decision reached as to whether the dose for the next cohort should be implemented. This decision will be based on
change in parasitemia from baseline, safety and tolerability, and exposure up to Day 14. 2-6 cohorts of adult patients (10 patients per
cohort) with acute, uncomplicated P. falciparum or P. vivax malaria will be run. In total, there will be a minimum of 20 and a maximum of
60 patients.
If success criteria for Cohort 1a are met, Cohort 2a will proceed with a lower exposure of SJ733. Likewise, if success criteria for
Cohort 1b are met, Cohort 2b will proceed with a lower dose of SJ733. For the purposes of this decision, a-series cohorts
(falciparum) will be treated independently from b-series (vivax) cohorts. If data from the first pair of cohorts do not meet the success
criteria, but are inconclusive, the same dosing regimen may be repeated. The same approach will be used for progress from the
second pair of cohorts to the third, but with the addition of the option to initiate a 3rd pair of cohorts, re-escalating SJ733 exposure by
dosing the combination of SJ733 (300 mg) + cobicistat (150 mg) for three consecutive days. Established antimalarial therapy will be
given if a patient meets any of the defined treatment failure criteria. 
Dosing within a dose cohort will be paused if one serious adverse event (SAE; Section 8.1.2) is noted while determination of
relatedness to study drug is being made. For a SAE, the decision of relatedness to study drug will ultimately be approved by the SRT
and DSMB. The DSMB will determine if the nature of the event allows continuation. No additional subjects in the cohort will be dosed
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if it is determined that the graded event meets the definition for stopping or if a second drug-related SAE is observed within that
cohort.
Cohorts 1a and 1b are expected to achieve roughly five-fold higher plasma exposure of (+)-SJ733 than Cohorts 2a and 2b. Thus, if
Cohorts 1a and 1b prove efficacious but repeated drug-related adverse events are observed, the Investigator, DSMB, and SRT may
unanimously agree that no further patients should be recruited to Cohorts 1 but that patient recruitment to Cohorts 2 should still be
pursued. In this scenario, the Investigator will assess the severity/intensity of the adverse reactions and clinical laboratory changes
using the DMID Toxicity Grading Scale for Determining the Severity of Adverse Events provided in Attachment 3 and Section 8.1.2.
This information will be relayed to the DSMB and SRT, who will make recommendations regarding further conduct of the trial, and if
considered necessary, may recommend pausing or stopping further administration of the investigational product. Cohort progression
will only be explored if the Investigator, DSMB, and SRT unanimously agree it is warranted and appropriate. These recommendations
will also be communicated to the Ethics Committee and Regulatory Authority and any necessary updates will be made to the patient
consent form.
Available Alternative Treatment(s): Describe alternative treatments and procedures that might be advantageous to the subjects,
should they choose not to participate in the study. This should include a discussion of the current standard of care treatment(s).
The alternative is to not participate in the study and receive the standard medical attention currently available for the treatment of
malaria. If the proposed experimental therapy is ineffective or not tolerated, patients will receive standard treatment from the study
physicians following the standard protocol for treating malaria according to current Peruvians standards. Patients maintain the right to
withdraw from the study and will receive the standard therapy at the conclusion of the study or at withdrawal to ensure resolution of
their malaria. Even if the experimental therapy is effective, all patients will receive the standard therapy at the completion of the trial. 
For P. falciparum mono-infection, a combination of Artesunate (AS) and Mefloquine (MQ), known as ASMQ, will be administered as
two fixed dose tablets (100 mg AS and 200 mg of MQ) given daily for three consecutive days and supplemented with three tablets
(15 mg each) of Primaquine phosphate (PQ) taken on the first day. 
For P. vivax mono-infection, patients will be dosed with 25 mg/kg of Chloroquine (CQ) given over three days (day 1: 4 tablets, day 2: 4
tablets, and day 3: 2 tablets) supplemented with two tablets (15 mg each) of Primaquine phosphate (PQ) taken daily for seven
consecutive days.
In the case of P. falciparum and P. vivax mixed infections, the ASMQ treatment regimen will be supplemented with two tablets (15 mg
each) of Primaquine phosphate (PQ) taken daily for seven consecutive days.
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Research Materials, Records and Privacy: Identify the sources of research material obtained from living human subjects. Indicate
what information (specimens, records, data, genetic information, etc.) will be recorded and whether use will be made of existing
specimens, records or data. Explain why this information is needed to conduct the study.
Return of Research Results or Incidental Findings (if applicable):
If research has the potential to identify individual results or discover incidental findings that could affect the health of a subject,
describe plans to assess, manage, and if applicable disclose findings with individual subjects or provide justification for not disclosing.
For IRB expectations, refer to the UK IRB “Frequently Asked Questions (FAQs) on the Return of Research Results or Incidental
Research Findings" [PDF].
The medical records gathered during this study will be obtained and processed in electronic form that is used only for investigative
purposes related to this study. These records may be reviewed by the Sponsor or their representatives, the, study team, Covance
Inc., the Peruvian Ministry of Health through known agencies like the National Health Institute (INS); the Director General autoridad
Nacional de Productos Farmacéuticos, Dispositivos médicos y productos sanitarios (ANM) (formerly DIGEMID, the United States
Food and Drug Administration (FDA), the regulatory authorities of other countries, and the Ethics Committee (both Peru and the
University of Kentucky located in the United States) in order to verify that the study is being carried out in the proper manner. 
Any information or specimens that are collected will be identified only by a number code assigned to each patient's file. The study
physician is responsible for tracking the list of codes that allow assigned number to be connected to individual patients. This list will
be kept at the study site to guarantee that in case of an emergency they can be identified and contacted. The list of codes will be kept
until the last request for commercialization of the research product has been received.
Blood samples (Safety, Efficacy, and Pharmacokinetic analysis) will be processed and de-identified at the ACSA site laboratory and
the Universidad Peruana Cayetano Heredia Laboratory. Samples will be stored for up to five years and then will be destroyed
following the destruction guidelines of the laboratory. Sample analysis will also be conducted at Instituto de Medicina Tropical
Alexander von Humboldt de la Universidad Peruana Cayetano Heredia located at located in Av. Honorio Delgado 430, San Martín de
Porres, Lima, Peru and Pyxant in Colorado, USA. The storage time allows the Sponsor to respond to regulatory questions related to
the study and re-check specific protocol parameters. After that time, any remaining samples will be destroyed following the guidelines
of the laboratory. Pyxant laboratories have processed pharmacokinetic samples for both the previously completed Phase 1a and
Phase 1b trials. They have a well validated analytical method and will continue to analyze the pharmacokinetic samples to enable
direct comparison to previously gathered data.
Patients will have the right to see and photocopy study-related records if the study physician has this information in his possession. At
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the end of the study worldwide, the study results will be available for the different national regulatory entities, including the INS in
Peru’s case, who will have the information available in Spanish on this webpage http://www.ensayosclinicos-repec.ins.gob.pe. In
addition, patients may ask the research doctor about the study results.
Confidentiality: Specify where the data and/or specimens will be stored and how the researcher will ensure the privacy and
confidentiality of both. Please address the following items or indicate if the following has been addressed in a HIPAA or Limited
Review form:
physical security measures (e.g., locked facility, limited access);
data security (e.g., password-protection, data encryption);
who will have access to the data/specimens and identifiers;
safeguards to protect identifiable research information (e.g., coding, links, certificate of confidentiality);
procedures employed when sharing material or data, (e.g., honest broker if applicable, written agreement with recipient not to re-
identify, measures to ensure that subject identifiers are not shared with recipients).
management after the study
Describe whether data/specimens will be maintained indefinitely or destroyed. If maintained, specify whether identifiers will be
removed from the maintained information/material. If identifiers will not be removed, provide justification for retaining them. If the
data/specimens will be destroyed, describe how and when the data/specimens will be destroyed. For multi-site studies, the PI
consults the study sponsor regarding retention requirements, but must maintain records for a minimum of six years after study closure.
Also, specify who will access the identified data/specimens, and why they need access. If applicable, describe what measures will be
taken to ensure that subject identifiers are not given to the investigator. If applicable, describe procedures for sharing data/specimens
with entities not affiliated with UK. 
HIPAA/FERPA Minimal Access Standards: The IRB expects researchers to access the minimal amount of identifiers to
conduct the study and comply with applicable HIPAA and Family Educational Rights and Privacy Act (FERPA) requirements.
If data are going to be collected, transmitted, and/or stored electronically, for appropriate procedures please refer to the
guidance document "Confidentiality and Data Security Guidelines for Electronic Data" [PDF].
Cloud storage: For storage of data on cloud services other than UK OneDrive, please verify security settings are sufficient
and in accordance with respective departmental, UK Corporate Compliance, and/or UK Information Technology
requirements.
Creation of digital data application/program: If a research protocol involves the creation and/or use of a computer program
or application, mobile or otherwise, please specify whether the program/application is being developed by a commercial
software developer or the research team and provide any relevant information regarding the security and encryption
standards used, how data is stored and/or transmitted to the research team, what information about the subjects the
program/application will collect, etc. For relevant information to include, see Considerations for Protocol Design Concerning
Digital Data [PDF]. The IRB may require software programs created or used for research purposes be examined by a
consultant with appropriate Internet technology expertise to ensure subject privacy and data are appropriately protected.
NIH-funded genomic research: The National Institutes of Health (NIH) Genomic Data Sharing (GDS) Policy sets forth
expectations that ensure the broad and responsible sharing of genomic research data consistent with the informed consent
of study participants from which the data was obtained. If you are submitting genomic data to an NIH data repository,
describe your NIH data sharing plan.
Management after study: Describe how the collected data/specimens will be managed after the end of the study. Specify
whether identifiers will be removed from the maintained information/material. If identifiers will not be removed, provide
justification for retaining them and specify what steps will be taken to secure the data/specimens (e.g., maintaining a coded
list of identifiers separate from the data/specimens).
If the data/specimens will be destroyed, describe how, when, and why this will be done. Note that destruction of primary data
may violate NIH and NSF retention and sharing requirements, journal publication guidance, and University Data-Retention
policies. Additionally, primary data may be necessary for other purposes (to validate reproducibility, for data sharing, or for
evidence in various investigations). PIs should carefully consider whether the destruction of data is justified.
The investigator is responsible for retaining signed consent and assent documents and IRB research records for at least six
years after study closure, as outlined in the Study Closure SOP [PDF]. If the research falls under the authority of the FDA or
other regulatory agencies, or a study sponsor is involved, additional requirements may apply.
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By signing the informed consent form, volunteers will give their consent for the study physician and his team to review their medical
records gathered during this study. These records, and the information in them, will be obtained and processed in electronic form that
is used only for investigative purposes related to this study. When we write about or share the results from the study, we will remove
any personal information and communicate about the combined information. The volunteer's name and other information that may
identify them will be kept private.
The volunteer's medical records may also be reviewed by the Sponsor (R. Kiplin Guy) or his representatives, the study team,
Covance Inc., the Peruvian Ministry of Health through known agencies like the National Health Institute (INS); the Director General
autoridad Nacional de Productos Farmacéuticos, Dispositivos médicos y productos sanitarios (ANM) (formerly DIGEMID, the United
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States Food and Drug Administration (FDA), the regulatory authorities of other countries, and the Ethics Committee (both Peru and
the University of Kentucky located in the United States) in order to verify that the study is being carried out in the proper manner.
These professionals have a commitment to respect the confidentiality of the information and will keep the volunteer's identity and
personal information confidential to the extent that the law permits. 
Peruvian regulations require that the study physician and/or study personnel protect the privacy of patients information. We will do
everything we can to prevent anyone who is not on the research team from knowing that the patients gave us information, or what that
information is. All the information collected will be assigned a number code and the patient's identity will remain unknown. The
patient's name and address will not be on the information that comes from the study center, so that they cannot be recognized by it.
Any information collected that may be transferred outside of the country to the University of Kentucky will be identified only by the
number code assigned to the patient's file. Still, absolute confidentiality cannot be guaranteed due to the need to share information in
the matters previously described.
The study physician (Dr. Llanos) is responsible for tracking the list of codes that allow the volunteer's assigned number to be
connected to their name. This list will be kept at the study site to guarantee that in case of an emergency they can be identified and
contacted. The list of codes will be kept until the last request for commercialization of the research product has been received.
The volunteer's samples will be processed at the ACSA site laboratory and the Universidad Peruana Cayetano Heredia Laboratory.
The samples will be stored for up to five years and then will be destroyed following the destruction guidelines of the laboratory
The coded samples will be stored for a maximum of five years after the last patient visit for the study at Instituto de Medicina Tropical
Alexander von Humboldt de la Universidad Peruana Cayetano Heredia located at located in Av. Honorio Delgado 430, San Martín de
Porres, Lima, Peru. The storage time allows the Sponsor to respond to regulatory questions related to the study and re-check
specific protocol parameters. After that time, any remaining samples will be destroyed following the guidelines of the laboratory.
Patient data will be logged into an Electronic Data Capture system at the site by the site. Where the data violate validation checks
queries will fire within the system for the Investigator to address and respond. 
Medications will be coded using the WHO-drug dictionary. Medical conditions and AEs will be coded using the latest version of the
MedDRA dictionary.
When data entry has been completed and all outstanding queries have been resolved for a CRF, the CRF will be eligible for QC
checking. A sample of 9 (i.e. ?n + 1) Patients will be selected for QC checks and 100% of these Patients’ data will be audited. In
addition, 100% of demography, parasite count, AEs and withdrawal data will be checked for all Patients. The highest acceptable error
rate for QC is 0.5%. A higher error rate will prompt a review of a further sample of 9 Patients. If the error rate remains above 0.5%, a
100% QC check of all data will be conducted. 
All errors discovered will be corrected on the database and the corrections will be audit-trailed and will undergo a QC check. On
satisfactory completion of the QC checks, the database will be locked.
Analytic data management will be performed with faculty and staff at the University of Kentucky. Methods for data transfer will involve a
secure platform (e.g. REDCap SendIt! Feature). Data transfer protocols from independent CRO to UK faculty and staff data
management team will be described in the data management plan (DMP). 
Analytic data management will utilize Research Electronic Data Capture (REDCap) as an electronic data management system.
REDCap is a software toolset and workflow methodology to manage research data for research studies. The consortium, initiated in
August 2006, has shared the software and methodology with the larger research community of CTSA-, GCRC- and RCMI-
participating institutions. The consortium is open to any academic institution, and members are provided with software and support at
no charge, with the expectation that participants will contribute back to the overall project. 
Limited study personnel will have administrative rights to make changes to the data, and all changes will be tracked through the
REDCap audit trail. The data entered into the REDCap database is stored on servers in the UK Research Data Management Center
and is backed-up on a regular basis. All raw datasets exported from REDCap as well as all analysis datasets are stored on
UKHealthcare servers behind the medical center firewall. Access will be limited to study personnel involved with data management
and data analysis.
SAS v9.4 or higher will be used to create and integrate any resulting datasets. SAS analysis datasets will be created, and SAS
programs will be developed to further investigate potential data issues via simple descriptive statistics and plots. Summary reports
will be provided periodically during the course of the project to verify accuracy of data entry and provide early opportunities for
clarification of questions and correction of errors and omissions. For analysis datasets, Data Definition Tables (DDTs) are included to
document all variables (both raw and derived) included in the analysis datasets. This includes the variable name, label, type, length,
format, coded values and logic for creating derived variables. All derived variables are independently programmed by two SAS
programmers and then compared using SAS PROC COMPARE. All differences are documented and changes are made to the SAS
code as necessary until the PROC COMPARE output is clean, i.e. showing no differences. For raw data, a data dictionary is available
through REDCap. The data dictionary provides a description of all data fields including the field name, label, field type, response
option coding and branching logic. 
Project data will include raw survey data stored in REDCap and analysis. All project data will be maintained on UK Healthcare servers
as described in the following section.
EDT Security: The EDT maintains a 900 square feet data center with independent power, cooling, and humidity control on the UK
campus. The entire workspace is secured by electronic access with logged entry and exit to all facility offices and monitored with a
security camera. The internal communication network is protected by multiple firewalls. All data on servers are sent to off-site backup
Section 8 Page 14 of 20
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each day. The network is managed by a full-time staff to support file servers, virtual machines, and the physical network. EDT
undergoes periodic comprehensive audits in addition to a security risk assessment through UK HealthCare IT Security that is
delivered bi-weekly. This includes a thorough review of Privacy and Confidentiality policies and procedures in addition to hardware
security. The objective of the security risk assessment is to identify opportunities for improvement, prioritize any needed remediation
activities, scope, and plan and remediate any found deficiencies. All source data, clinical records and laboratory data relating to the
study will be retained in the archive for a minimum of 15 years after the completion of the study. Written agreement from the Sponsor
must precede destruction of the same.
Study documents will be retained for a minimum of 2 years after the last approval of a marketing application in an ICH region and until
there are no pending or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the formal
discontinuation of clinical development of the investigational product. These documents will be retained for a longer period, however,
if required by local regulations. No records will be destroyed without the written consent of the Sponsor, if applicable. It is the
responsibility of the Sponsor to inform the investigator when these documents no longer need to be retained.
Long term storage of the trial data will utilize the University of Kentucky’s (UK) Center for Clinical and Translational Science (CCTS)
Biomedical Informatics (BMI) Core and CCTS Enterprise Data Trust (EDT). The EDT was developed by the CCTS Biomedical
Informatics (BMI) Core. The EDT combines operational data from a number of different electronic systems into a single, data store,
where the data is placed into standard forms, integrated, validated, and optimized for efficient, accurate retrieval. The EDT
infrastructure includes a virtualized environment that supports individual virtual machines (VM) for researchers accessing data and
resources. Each VM is configured with the preferred operating system (Windows, Ubuntu, Linux) and statistical software or tools
(Excel, R, SAS, SPSS, Tableau) required for each project. VM’s are configured/provisioned to best practice and continually
monitored via VROP for compliance and performance. In most cases, VM’s can be modified to optimize performance if necessary.
The EDT provides highly secure and monitored environments to support special data collections included Center for Medicare &
Medicaid Services (CMS) datasets for several investigators.
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Payment: Describe the incentives (e.g., inducements) being offered to subjects for their time during participation in the research
study. If monetary compensation is offered, indicate how much the subjects will be paid and describe the terms and schedule of
payment. (It is IRB policy that provision should be made for providing partial payment to subjects who withdraw before the completion
of the research. Monetary payments should be prorated or paid in full.)
There will be no monetary incentives for participation itself. There will be reimbursement of up to 85 Peruvian soles (~$25 USD) for
each day that the patient misses work (lost wages) to go to the site for participating in the study, either for admission to study,
receiving treatment, and follow-up appointments. In addition, they will be reimbursed up to a maximum of 50 Peruvian soles (~$15
USD) per visit for any transportation expenses, communication and food expenses incurred for the visits related to the study.
The reimbursement amounts were suggested by the clinical lead and his team and are based on clinical trials conducted at ACSA
with the same target patient population over the last 5 years. These amounts have also been reviewed by the local Peruvian ethics
committee (latest communication included as an attachment in the Additional Information Section). Patients will be recruited from 14
villages that have health posts in the districts of Iquitos, San Juan Bautista, and Punchana. Some are located along the road and
others at the edges of the rivers. The distance by land or river to the city of Iquitos is less than 1.5 hours, most less than 1 hour. In
general, the people who live in these recruitment areas are representative of the general population that suffers malaria in the
Amazon region. They are generally mestizo and do not live in extreme poverty. However, they do depend on daily wages to support
their family and most do not have personal vehicles and therefore must hire a combination of water taxi and rickshaw drivers to travel
to the clinical site.
Costs to Subjects: Describe any costs for care associated with research (including a breakdown of standard of care procedures
versus research procedures), costs of test drugs or devices, and research procedure costs that are the subject’s responsibility as a
consequence of participating in the research. Describe any offer for reimbursement of costs by the sponsor for research related injury
care.
There will be no cost to subjects for participating in the trial. They may incur lost wages and travel costs when staying at the clinic or
visiting test site for follow-up visits and they will be reimbursed as outlined above.
Data and Safety Monitoring: The IRB requires review and approval of data and safety monitoring plans for greater than minimal risk
research, clinical research, or NIH-funded/FDA-regulated clinical investigations. 
If you are conducting greater than minimal risk research, clinical research, or your clinical investigation is NIH-funded/FDA-regulated,
describe your Data and Safety Monitoring Plan (DSMP). Click here for additional guidance on developing a Data and Safety Monitoring
Plan. 
If this is a non-sponsored investigator-initiated protocol considered greater than minimal risk research, clinical research, or your
clinical investigation is FDA-regulated, and if you are planning on using a Data and Safety Monitoring Board (DSMB) as part of your
DSMP, click here for additional guidance for information to include with your IRB application.
If relying on an independent agent or committee for DSMB services, it is the PI’s responsibility to establish the services with the agent
or committee. Please be reminded that the PI must submit DSMB reports to the IRB via modification or continuing review. 
Section 8 Page 15 of 20
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We have contracted Covance to oversee Peruvian work, including regulatory submissions, medical and safety monitoring,
pharmacovigilance, and site monitoring. 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and interviews of a study
participant presenting for medical care, or upon review by a study monitor. All AEs including local and systemic reactions not meeting
the criteria for SAEs will be captured on the appropriate CRF. Information to be collected includes event description, time of onset,
clinician’s assessment of severity, relationship to study product (assessed only by those with the training and authority to make a
diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study must be documented appropriately
regardless of relationship. All AEs will be followed to adequate resolution. 
All SAEs, occurring after the signing of the ICF until the End of Study visit or up to 42 days after last dose of study drug, and
regardless of study drug relationship, must be reported, within 24 hours of obtaining knowledge of the event, to the Contract
Research Organization (CRO). The CRO will inform the Sponsor on the same day.
The SAE form will collect data surrounding the event (e.g. the nature of the symptom[s], time of onset in relation to initiation of
therapy, duration, intensity, and whether or not therapy was interrupted or discontinued). The Investigator’s assessment of the
probable cause of the event will also be included. In addition, relevant medical history, concomitant medications, laboratory and
diagnostic tests reports, and procedures as well as all pertinent medical information related to the event will also be collected. 
The investigator or study site personnel will provide the initial notification by completing the SAE page in the eCRF. The SAE form
must include the investigator’s assessment of the relationship of the event to the study drug and must include the investigator’s
signature. Even if minimal information is available, it is imperative that the investigator always makes an assessment of causality, as
causality assessment is one of the requirements for regulatory reporting. Based on the follow up information received the investigator
can change his/her causality assessment and amend the SAE form accordingly.
Covance Pharmacovigilance will forward SAE queries directly to the investigator requesting additional information. It is the
investigator’s responsibility to be diligent in providing this information as soon as it is available.
If an event meets serious criteria and it is not possible to access the EDC, the SAE will be submitted electronically using this email
address: SAEIntake@covance.com or FAX# 1 609 419 2609. If email access is not available, the SAE will be reported
telephonically using a toll free number corresponding to the country (see Safety Management Plan)
If Covance Pharmacovigilance becomes aware of the case via a telephone call, the pharmacovigilance representative will document
the event details on a telephone contact log which will be filed with the case. A request for a completed SAE form will be emailed to
the Investigator site and the Covance Project Manager and Site Monitor will be notified. 
Dates should be recorded in the DD/MMM/YYYY format, e.g. 01/JAN/2012. All personal health identifying information (PHI) must be
deleted, which may identify the patient from supporting documents. (e.g. patient name, address). The investigator or study site
personnel to call the site monitor with any questions regarding the completion of the SAE form.
All SAEs will be followed until satisfactory resolution or until the site investigator deems the event to be chronic or the adherence to
be stable. 
It is the responsibility of the Sponsor to determine whether a reported SAE fits the classification of a SUSAR and to notify the
investigator of their decision as soon as possible. It is the responsibility of the Sponsor to determine whether an event requires
expedited reporting and to notify the investigator of their decision as soon as possible.
Any SAE/SAR/SUSAR, irrespective of causality assessment to study drug and expectedness per IB, must be reported to the
Regulatory Authority by University of Kentucky or delegate and to the relevant EC by the PI or delegate within 7 calendar days after
the Sponsor becomes aware of the event. If the initial report is incomplete, a complete report must be submitted within 8 days of
sending the first response. If significant new information is received by University of Kentucky on a case already reported, the clock
starts again, and this should be provided as a follow-up report within 15 calendar days of receipt of the information.
A SUSAR that is not fatal or life-threatening must be reported to the Regulatory Authority by University of Kentucky or delegate and to
the EC by the PI or delegate and in any event within 15 calendar days after University of Kentucky first becomes aware of the event. 
SAEs/SARs/SUSARs must be recorded and reported whether or not the investigator considers the SAE/SARs/SUSAR to be related
to SJ733.
Photocopies of results, consultant report(s), a summary of the outcome of the reaction and the investigator's opinion of SJ733
relationship to the SAE/SUSAR will accompany the SAE form if and when available.
If any information relating to the study drug in a study becomes available after the submission of a final protocol to the competent
authority, which may impact on the conduct of the study, including but not limited to the risk and benefit evaluations underpinning
approvals and volunteers consent, University of Kentucky will notify the Investigator in writing as soon as practically possible and the
parties will agree, in writing, what steps need to be taken, if any. 
The Investigator will be required to provide the following information:
• Patient’s ID number, date of birth and gender
• Description of the event
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o Date, time of onset
o Clinical history
o Associated signs and symptoms
o Temporal association with the study drug
o Medical management, including rationale
o Pertinent laboratory tests
o Severity (see definition or toxicity score)
o Causal relationship to the study drug with investigator’s rationale for causality assessment
• Other information
o Relevant past medical history
o Concomitant medications
o Autopsy report or expectation of an autopsy in the case of death
• Outcome of the event
o Date, time of resolution, if resolved
• Documentation of notification to the EC by the Investigator
Any medical condition that is present at the time that the participant is screened will be considered as baseline and not reported as an
AE. However, if the study participant’s condition deteriorates at any time during the study, it will be recorded as an AE. UPs will be
recorded in the data collection system throughout the study. 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at each level of severity to
be performed. AEs characterized as intermittent require documentation of onset and duration of each episode. 
The PI will record all reportable events with start dates occurring any time after informed consent is obtained until 7 (for non-serious
AEs) or 30 days (for SAEs) after the last day of study participation. At each study visit, the investigator will inquire about the
occurrence of AE/SAEs since the last visit. Events will be followed for outcome information until resolution or stabilization.
Additionally the Study will have an SRT and DSMB. The members of the Safety Review Team (SRT) are responsible for decisions
related to the safety of patients and the continuation of the study. The SRT will assess preliminary safety, efficacy and
pharmacokinetic data (if available) up to Day 14 of the first four patients enrolled, and thereafter upon completion of Day 14
assessments of each cohort and whenever else indicated as a result of safety concerns. The SRT will decide on the appropriateness
of subsequent doses to be administered and continuation of the study.
The SRT will consist of the following people:
• the Principal Investigator (clinical lead - Dr. Llanos)
• the Sponsor (Dr. Guy)
• the Medical Monitor
• the Project Director
The SRT will be advised by the Data and Safety Monitoring Board (DSMB) and will attend the non-voting sessions of the DSMB
Meetings. During the study, an external and independent DSMB appointed by the Sponsor will meet to review study data. The board
will consist of at least the following voting members:
• a Statistician
• two independent Medical Experts
The DSMB will meet at least semiannually to assess safety and efficacy data on each arm of the study. The DMSB will operate under
the rules of an approved charter that will be written and reviewed at the organizational meeting of the DSMB. At this time, each data
element that the DSMB needs to assess will be clearly defined. The DSMB will provide its input to the study Sponsor. 
The timing of the DSMB reviews and scope of the data review will be detailed in the DSMB Charter. The DSMB will be required to
review the safety and efficacy data upon completion of Day 14 assessments of each cohort, and whenever else as indicated by
safety concerns. The DSMB members will also be informed of and review all SAEs and AESIs as and when they are reported. All
procedures associated with DSMB reviews, including objectives, data handling and elements for review will be documented in the
DSMB Charter. Meeting discussions and decisions will be documented in DSMB minutes. Voting sessions of the DSMB will be
attended only by designated DSMB members.
Based on its review, the DSMB will make recommendations to the SRT regarding further conduct of the trial, and if considered
necessary, may recommend pausing or stopping further administration of the investigational product. These recommendations will
also be communicated to the Ethics Committee and Regulatory Authority as required.
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Subject Complaints: Describe procedures (other than information provided in consent document) for handling subject complaints or
requests for information about the research. The procedures should offer a safe, confidential, and reliable channel for current,
prospective, or past research subjects (or their designated representative) permitting them to discuss problems, concerns and
questions, or obtain information.
If the patients have any questions, comments, or complaints regarding any part of the study, or in case of harm related to the trial, or if
they have an adverse reaction, they are requested to immediately contact:
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Dr. Elmer Alejandro Llanos-Cuentas
Address: Asociación Civil Selva Amazónica (ACSA)
Urb. Jardín N.° 27 (altura cuadra 4 Av. Fanning)
Iquitos - Loreto
Telephone: 994 273 050
E-mail: elmer.llanos@upch.pe
If they have any concerns or questions about their rights as a volunteer in this research, they are encouraged to contact staff at the
Comité Institucional de Bioética (CIB) de VÍA LIBRE:
• Ethich Committe Chairman: Lic. Karen Cruz Azaña
• Telephone: (+511) 203-9900 Monday to Friday from 09 am to 18 hrs
• Address: Jr. Paraguay 490, Cercado de Lima, Lima, Perú
• e-mail: comitebioetica@vialibre.org.pe
An Ethics Committee is a group of members who are impartial and independent to the medical investigators, and their function is
overseeing the respect of the dignity and rights of the participants in the design and performance of the research projects.
Finally, if they believe their rights are violated or for any complaint, they can contact the National Institute of Health (General Office of
Research and Technology Transfer, OGITT) regulatory agency for Peruvian clinical trials, through the following telephone number:
748 1111 extension 2191 or by written communication through the following e-mail: consultaensayos@ins.gob.pe, or by a formal
document submitted through the Filing Desk of the institution or by appearing in person to the OGITT at the following address: Capac
Yupanqui 1400, Jesús María, Lima 11.
 
Does your research involve Non-English Speaking Subjects or Subjects from a Foreign Culture?
Yes
No
Non-English Speaking Subjects or Subjects from a Foreign Culture
Describe how information about the study will be communicated to potential subjects appropriate for their culture, and if
necessary, how new information about the research may be relayed to subjects during the study.
Include contact information for someone who can act as a cultural consultant for your study.  The person should be familiar
with the culture of the subject population and/or be able to verify that translated documents are the equivalent of the
English version of documents submitted. The consultant should not have any direct involvement with the study. If you do
not know someone who would be willing to act as your cultural consultant, the Office of Research Integrity will try to find
someone to fill this role (this may delay the approval process for your protocol). Please include the name, address,
telephone number, and email of the person who will act as the cultural consultant for your study.  For more details, see the
IRB Application Instructions on Research Involving Non-English Speaking Subjects or Subjects from a Foreign Culture.
For recruitment of Non-English speaking subjects, the consent document needs to be in the subject’s native language. 
Download the informed consent template available in the E-IRB "Informed Consent/Assent Process" section and use it as
a guide for developing the consent document. (Note: Your translated consent document can be attached to your
application in the “Informed Consent" section; be sure to save your responses in this section first.)
If research is to be conducted at an international location, identify local regulations, laws, or ethics review requirements for
human subject protection. If the project has been or will be reviewed by a local Ethics Committee, attach a copy of the
review to the UK IRB using the attachment button below. You may also consult the current edition of the International
Compilation of Human Research Standards
All documents pertaining to the study have been translated to Spanish, the local language in Iquitos, Peru by an independent
certified translator. Translator asked a Peruvian colleague to be a cultural consultant to ensure the Spanish would be familiar
to the people of Iquitos, Peru. Contact information is: 
Daniella Razuri Váquez 
Francisco de Zela 2086 - Lince - Lima - Lima - Perú 
(+51)959392674
daniella.razuri@gmail.com
Study is currently being reviewed by the Peruvian Ethics Committee and CRO Covance Peru Services, S.A. is the Legal
Representative in country and has facilitated the submission to the Peruvian EC ensuring local regulations, laws, and ethics
review requirements are met.
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Does your study involve HIV/AIDS research and/or screening for other reportable diseases (e.g., Hepatitis C, etc…)?
Yes
No
HIV/AIDS Research
If you have questions about what constitutes a reportable disease and/or condition in the state of Kentucky, see ORI’s
summary sheet: “Reporting Requirements for Diseases and Conditions in Kentucky" [PDF].
HIV/AIDS Research: There are additional IRB requirements for designing and implementing the research and for
obtaining informed consent. Describe additional safeguards to minimize risk to subjects in the space provided below.
For additional information, visit the online IRB Survival Handbook to download a copy of the "Medical IRB's requirements
for Protection of Human Subjects in Research Involving HIV Testing" [D65.0000] [PDF], and visit the Office for Human
Research Protections web site for statements on AIDS research, or contact the Office of Research Integrity at 859-257-
9428.
PI-Sponsored FDA-Regulated Research
Is this an investigator-initiated study that:                                                                                                                                                 
         Back to Top
1) involves testing a Nonsignificant Risk (NSR) Device, or
2) is being conducted under an investigator-held Investigational New Drug (IND) or Investigational Device Exemption (IDE)?
Yes
No
PI-Sponsored FDA-Regulated Research
If the answer above is yes, then the PI assumes the regulatory responsibilities of both the investigator and sponsor. The Office
of Research Integrity provides a summary list of sponsor IND regulatory requirements for drug trials [PDF], IDE regulatory
requirements for SR device trials [PDF], and abbreviated regulatory requirements for NSR device trials [PDF]. For detailed
descriptions see FDA Responsibilities for Device Study Sponsors or FDA Responsibilities for IND Drug Study Sponsor-
Investigators.
Describe your (the PI’s) experience/knowledge/training (if any) in serving as a sponsor (e.g., previously held an IND/IDE);
and
Indicate if you have transferred any sponsor obligations to a commercial sponsor, contract research organization (CRO),
contract monitor, or other entity (provide details or attach FDA 1571).
The Sponsor, Rodney Kiplin Guy, is acting as individual person. He is the current holder of the US IND under which SJ733 is
being developed.
The Sponsor´s research is focused on the discovery and development of novel small molecules that target the pathophysiology
of oncology and protozoal infectious diseases. The Sponsor’s work places a major focus on discovering new therapeutic
chemotypes, determining their mechanism of action, and conducting proof-of-concept studies in
pharmacokinetic/pharmacodynamic (PK/PD) models of disease. All the projects are intended to deliver well-validated
compounds that have suitable pharmacokinetic and toxicology profiles for detailed in vivo studies and provide a chemical lead to
start drug discovery. To date, the Sponsor’s work has identified dozens of potential new leads for these diseases with novel
mechanisms of action or novel applications. The Sponsor has contributed to repurposing drugs for clinical trials for
ependymoma, infantile ALL, and medulloblastoma; contributed a repurposed clinical candidate for retinoblastoma; and produced
a novel clinical candidate for malaria, (+)-SJ733, which is the subject of the proposed clinical trial.
Most relevant publications selected from over 150 peer reviewed papers: 
a. Guiguemde WA, et al. Chemical genetics of Plasmodium falciparum. Nature 2010, 465, 311-331.
b. Jimenez-Diaz, M.B et al. (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated
clearance of Plasmodium. Proc. Natl. Acad. Sci. U. S. A., 2014, 111, E5455-E5462.
c. Floyd, D.M. et al Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides. J. Med. Chem., 2016, 59,
7350-7362.
d. Gaur, A.H. et al. Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4
inhibitor (SJ733): a first-in-human and induced blood stage malaria phase 1a/ 1b study. Lancet Infect. Dis., 2020, 
Published Online April 7, 2020: https://doi.org/10.1016/S1473-3099(19)30611-5. 
He has been intimately involved in the previously completed Ph1a/1b trials:
NCT02661373 - Phase 1a, First-In-Human, Dose-Escalation Study of (+)-SJ000557733 (SJ733), an Oral, Novel Inhibitor of
Plasmodium Falciparum Plasma Membrane Protein PfATP4
NCT02867059 - A Proof-of-concept Study to Assess the Effect of (+)-SJ000557733 (SJ733) Against Early Plasmodium
Falciparum Blood Stage Infection in Healthy Participants
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IRB policy requires mandatory training for all investigators who are also FDA-regulated sponsors (see Sponsor-Investigator
FAQs). A sponsor-investigator must complete the applicable Office of Research Integrity web based training, (drug or
device) before final IRB approval is granted.
Has the PI completed the mandatory PI-sponsor training prior to this submission?
Yes
No
If you (the PI) have completed equivalent sponsor-investigator training, you may submit documentation of the content for the
IRB’s consideration.
Attachments
Section 8 Page 20 of 20
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HIPAA
Is HIPAA applicable?
Yes
No
(Visit ORI's Health Insurance Portability and Accountability Act (HIPAA) web page to determine if your research falls under the HIPAA
Privacy Regulation.)
If yes, check below all that apply and attach the applicable document(s): 
HIPAA De-identification Certification Form
HIPAA Waiver of Authorization
Attachments
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STUDY DRUG INFORMATION
The term drug may include:
FDA approved drugs,
unapproved use of approved drugs,
investigational drugs or biologics,
other compounds or products intended to affect structure or function of the body, and/or
complementary and alternative medicine products such as dietary supplements, substances generally recognized as safe (GRAS)
when used to diagnose, cure mitigate, treat or prevent disease, or clinical studies of e-cigarettes examining a potential therapeutic
purpose.
Does this protocol involve a drug including an FDA approved drug; unapproved use of an FDA approved drug; and/or an
investigational drug?
Yes
No
If yes, complete the questions below. Additional study drug guidance.
LIST EACH DRUG INVOLVED IN STUDY IN THE SPACE BELOW
Drug Name:
SJ733 ((+)-SJ000557733) in an investigational
new drug
cobicistat (Tybost®) is an FDA approved
CYP3A4 inhibitor used as "pharmacoenhancer"
for boosting exposures to CYP3A4 substrates
and more particularly human immunodeficiency
virus (HIV) drugs. In our study it will be used to
boost exposure of SJ733.
Note: Inpatient studies are required by Hospital Policy to utilize the Investigational Drug Service (IDS). Use of IDS is
highly recommended, but optional for outpatient studies. Outpatient studies not using IDS services are subject to
periodic inspection by the IDS for compliance with drug accountability good clinical practices. 
Indicate where study drug(s) will be housed and managed:
Investigational Drug Service (IDS) UK Hospital
Other Location:
This is an international study only. There will be
no participants enrolled at the University of
Kentucky
Is the study being conducted under a valid Investigational New Drug (IND) application?
Yes
No
If Yes, list IND #(s) and complete the following:
IND# 126652
IND Submitted/Held by:
Sponsor:
Held By: Rodney Kiplin Guy
Investigator:
Held By: Rodney Kiplin Guy
Other:
Held By:
Checkmark if the study is being conducted under FDA’s Expanded Access Program (e.g., Treatment
IND) or if this is an Individual Patient Expanded Access IND (FDA Form 3926).
FDA's Expanded Access Program Information for Individual Patient Expanded Access INDs, and
attach the following:
Section 10 Page 1 of 2
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FDA Form 3926;
FDA expanded access approval or correspondence;
Confirmation of agreement from manufacturer or entity authorized to provide access to the
product.
For guidance and reporting requirements at the conclusion of treatment see the "Expanded Access
SOP" [PDF].
Please also complete and attach the Study Drug Form (PDF) (required):
Attachments
Attach
Type
File Name
StudyDrug 300mg capsule CofA L0700840.pdf
StudyDrug 300mg capsule CofA L0700840_ES-LA.docx
StudyDrug Eisai Label Text_United States_en_es.docx
StudyDrug Tybost latest product label.pdf
StudyDrug Tybost latest product label(es)-proofread.pdf
StudyDrug SJ733_UK_Study_Drug_Form.pdf
StudyDrug Cobi_UK_Study_Drug_Form.pdf
StudyDrug 20200501_SJ733_Investigators_Brochure_en.docx
StudyDrug 20200501_SJ733_Investigators Brochure_es.docx
StudyDrug GMP Certificate_KCM_18FEB16.pdf
StudyDrug SN0023 (2020 Ann Rpt).pdf
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STUDY DEVICE INFORMATION
A DEVICE may be a:
component, part, accessory;
assay, reagent, or in-vitro diagnostic device;
software, digital health, or mobile medical app;
other instrument if intended to affect the structure or function of the body, diagnose, cure, mitigate, treat or prevent disease; or
a homemade device developed by an investigator or other non-commercial entity and not approved for marketing by FDA.
For additional information, helpful resources, and definitions, see ORI's Use of Any Device Being Tested in Research web page.
Does this protocol involve testing (collecting safety or efficacy data) of a medical device including an FDA approved device,
unapproved use of an approved device, humanitarian use device, and/or an investigational device?
Yes
No
[Note: If a marketed device(s) is only being used to elicit or measure a physiologic response or clinical outcome, AND, NO data will
be collected on or about the device itself, you may answer “no” above, save and exit this section, (Examples: a chemo drug study
uses an MRI to measure tumor growth but does NOT assess how effective the MRI is at making the measurement; an exercise study
uses a heart monitor to measure athletic performance but no safety or efficacy information will be collected about the device itself, nor
will the data collected be used for comparative purposes against any other similar device).]
If you answered yes above, please complete the following questions.
LIST EACH DEVICE BEING TESTED IN STUDY IN THE SPACE BELOW
Device Name:
Is the study being conducted under a valid Investigational Device Exemption (IDE)
or Humanitarian Device Exemption (HDE) application? See UK HUD SOP (PDF) for guidance.
Yes
No
If Yes, list IDE or HDE #(s) and complete the following:
IDE/HDE Submitted/Held by:
Sponsor:
Held By:
Investigator:
Held By:
Other:
Held By:
 Check if this is a Treatment or Compassionate Use IDE under the Food and Drug Administration
(FDA) Early Expanded Access program.
For Individual or Small Group Expanded Access, see FDA's Early Expanded Access Program
Information, and attach the following:
FDA expanded access approval or sponsor’s authorization;
An independent assessment from an uninvolved physician, if available;
Confirmation of agreement from manufacturer or entity authorized to provide access to the
product.
For guidance and reporting requirements at the conclusion of treatment see the “Medical Device
Clinical Investigations, Compassionate Use, and Treatment IDE SOP" [PDF]
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Does the intended use of any device used in this study meet the regulatory definition of Significant Risk (SR) device?
Yes. Device(s) as used in this study presents a potential for serious risk to the health, safety, or welfare of a subject and (1) is
intended as an implant; or (2) is used in supporting or sustaining human life; or (3) is of substantial importance in diagnosing,
curing, mitigating or treating disease, or otherwise prevents impairment of human health; or (4) otherwise presents a potential
for serious risk to the health, safety, or welfare of a subject.
No. All devices, as used in this study do not present a potential for serious risk to the health, safety, or welfare of
subjects/participants.
Please also complete and attach the Study Device Form (PDF) (required):
Attachments
Section 11 Page 2 of 2
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List all other non-UK owned/operated locations
where the research will be conducted:*
*A letter of support and local context is required from
non-UK sites. See Letters of Support and Local
Context on the IRB Application Instructions - Off-Site
Research web page for more information.
RESEARCH SITES
In order for this section to be considered complete, you must click "SAVE" after ensuring all responses are accurate.
A) Check all the applicable sites listed below at which the research will be conducted. If none apply, you do not need to check any
boxes.
UK Sites
UK Classroom(s)/Lab(s)
UK Clinics in Lexington
UK Clinics outside of Lexington
UK Healthcare Good Samaritan Hospital
UK Hospital
Schools/Education Institutions
Fayette Co. School Systems *
Other State/Regional School Systems
Institutions of Higher Education (other than UK)
*Fayette Co. School systems, as well as other non-UK
sites, have additional requirements that must be
addressed. See ORI's IRB Application Instructions -
Off-site Research web page for details.
Other Medical Facilities
Bluegrass Regional Mental Health Retardation Board
Cardinal Hill Hospital
Eastern State Hospital
Norton Healthcare
Nursing Homes
Shriner’s Children’s Hospital
Veterans Affairs Medical Center
Other Hospitals and Med. Centers
Correctional Facilities
Home Health Agencies
International Sites
Clínica de la Asociación Civil Selva
Amazónica (ACSA), Iquitos, Loreto - Peru
Attachments
Attach Type
File Name
-Letter of Support & Local Context
Letter of support ALLC 22May2020.pdf
-Letter of Support & Local Context
ACSA Clinical Site detailed.docx
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B) Is this a multi-site study for which you are the lead investigator or UK is the lead site?
Yes
No
If YES, you must describe the plan for the management of reporting unanticipated problems, noncompliance, and submission of
protocol modifications and interim results from the non-UK sites in the E-IRB "Research Description" section under Resources.
If the non-UK sites or non-UK personnel are engaged in the research, there are additional federal and university requirements which
need to be completed for their participation, such as the establishment of a cooperative IRB review agreement with the non-UK site.
Questions about the participation of non-UK sites/personnel should be discussed with the ORI staff at (859) 257-9428.
Section 12 Page 2 of 2
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RESEARCH ATTRIBUTES
Indicate the items below that apply to your research. Depending on the items applicable to your research, you may be required to
complete additional forms or meet additional requirements. Contact the ORI (859-257-9428) if you have questions about additional
requirements.
Not applicable
Check All That Apply
Academic Degree/Required Research
Aging Research
Alcohol Abuse Research
Cancer Research
Certificate of Confidentiality
CCTS-Center for Clinical & Translational Science
Clinical Research
Clinical Trial
Clinical Trial Multicenter(excluding NIH Cooperative Groups)
Clinical Trial NIH cooperative groups (i.e., SWOG, RTOG)
Clinical Trial Placebo Controlled Trial
Clinical Trial UK Only
Collection of Biological Specimens
Collection of Biological Specimens for Banking
Community-Based Participatory Research
Data & Safety Monitoring Board
Data & Safety Monitoring Plan
Deception
Drug/Substance Abuse Research
Educational/Student Records (e.g., GPA, test scores)
Emergency Use (Single Patient)
Genetic Research
Gene Transfer
GWAS (Genome-Wide Association Study) or NIH-funded study
generating large scale genomic data
International Research
Internet Research
Planned Emergency Research Involving Waiver of Informed
Consent
Pluripotent Stem Cell Research
Recombinant DNA
Survey Research
Transplants
Use of radioactive material, ionizing radiation, or x-rays [Radiation
Safety Committee review required]
Vaccine Trials
Click applicable listing(s) for additional
requirements and/or information:
Cancer Research (MCC PRMC)
Certificate of Confidentiality (look up
"Confidentiality/Privacy...")
CCTS (Center for Clinical and Translational
Science)
Clinical Research (look up "What is the definition
of....)
Clinical Trial (look up "What is the definition of....)
Determine if research meets NIH definition of
clinical trial;
*Reminder: Ensure compliance with
applicable requirements including:
Clinicaltrials.gov registration;
Good Clinical Practice (GCP) training; and
Consent Posting Requirement [PDF] for
federal funded trials.
Collection of Biological Specimens for Banking
(look up "Specimen/Tissue Collection...")
Collection of Biological Specimens (look up
"Specimen/Tissue Collection...")
Community-Based Participatory Research (look
up "Community-Engaged...")
Data & Safety Monitoring Board (DSMB)
*For Medical IRB: Service Request Form for
CCTS DSMB
Data & Safety Monitoring Plan
Deception*
*For deception research, also go to the E-IRB
Application Informed Consent section,
checkmark and complete "Request for Waiver
of Informed Consent Process"
Emergency Use (Single Patient) [attach
Emergency Use Checklist] (PDF)
Genetic Research (look up "Specimen/Tissue
Collection...")
Gene Transfer
HIV/AIDS Research (look up "Reportable
Diseases/Conditions")
Screening for Reportable Diseases [E2.0000]
(PDF)
International Research (look up "International &
Non-English Speaking")
NIH Genomic Data Sharing (GDS) Policy (PDF)
Planned Emergency Research Involving Waiver
of Informed Consent*
*For Planned Emergency Research Involving
Waiver of Informed Consent, also go to the E-
IRB Application Informed Consent section,
checkmark and complete "Request for Waiver
of Informed Consent Process"
Section 13 Page 1 of 2
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Use of radioactive material, ionizing radiation or
x-rays for research
Section 13 Page 2 of 2
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FUNDING/SUPPORT
If the research is being submitted to, supported by, or conducted in cooperation with an external or internal agency or funding program,
indicate below all the categories that apply. 
Not applicable
Check All That Apply
Grant application pending
(HHS) Dept. of Health & Human Services
(NIH) National Institutes of Health
(CDC) Centers for Disease Control &
Prevention
(HRSA) Health Resources and Services
Administration
(SAMHSA) Substance Abuse and
Mental Health Services Administration
(DoJ) Department of Justice or Bureau of
Prisons
(DoE) Department of Energy
(EPA) Environmental Protection Agency
Federal Agencies Other Than Those
Listed Here
Industry (Other than Pharmaceutical
Companies)
Internal Grant Program w/ proposal
Internal Grant Program w/o proposal
National Science Foundation
Other Institutions of Higher Education
Pharmaceutical Company
Private Foundation/Association
U.S. Department of Education
State
Click applicable listing(s) for additional requirements and/or information:
(HHS) Dept. of Health & Human Services
(NIH) National Institutes of Health
(CDC) Centers for Disease Control & Prevention
(HRSA) Health Resources & Services Administration
(SAMHSA) Substance Abuse & Mental Health Services Administration
Industry (Other than Pharmaceutical Companies) [IRB Fee Info]
National Science Foundation
(DoEd) U.S. Department of Education [PDF]
DoJ) Department of Justice or Bureau of Prisons ([PDF]
(DoE) Department of Energy Summary [PDF] and Department of
Energy Identifiable Information Compliance Checklist [PDF]
(EPA) Environmental Protection Agency [PDF]
Other:
Global Health Innovative
Technology Fund (GHIT) is an
international public-private
partnership between the
Government of Japan, multiple
pharmaceutical companies, the
Bill & Melinda Gates Foundation,
Wellcome Trust, and United
Nations Development
Programme (UNDP)
Specify the funding source and/or cooperating organization(s) (e.g., National Cancer Institute, Ford Foundation, Eli Lilly
& Company, South Western Oncology Group, Bureau of Prisons, etc.):
 
Global Health Innovative Technology
Fund (GHIT) - Awarded 
Grant# 3048113588
Grant title: Phase 2 Trial of SJ733, a
Novel PfATP4 Inhibitor for Malaria
Add Related Grants
If applicable, please search for and select the OSPA Account number or Electronic Internal Approval Form (eIAF) #
(notif #) associated with this IRB application using the "Add Related Grants" button. 
Section 14 Page 1 of 2
53333


If required by your funding agency, upload your grant using the "Grant/Contract Attachments" button.
Add Related Grants
Grant/Contract Attachments
Attach Type
File Name
GrantContract
G2016-226_R1.pdf
The research involves use of Department of Defense (DoD) funding, military personnel, DoD facilities, or other DoD resources.
(See DoD SOP [PDF] and DoD Summary [PDF] for details)
Yes
No
Using the “attachments” button (below), attach applicable materials addressing the specific processes described in
the DoD SOP.
DOD SOP Attachments
Additional Certification: (If your project is federally funded, your funding agency may request an Assurance/ Certification/Declaration
of Exemption form.) Check the following if needed:
Protection of Human Subjects Assurance/Certification/Declaration of Exemption (Formerly Optional Form – 310)
Section 14 Page 2 of 2
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OTHER REVIEW COMMITTEES
If you check any of the below committees, additional materials may be required with your application submission.
Does your research fall under the purview of any of the other review committees listed below? [If yes, check all that apply and attach
applicable materials using the attachment button at the bottom of your screen.]
Yes
No
Institutional Biosafety Committee
Radiation Safety Committee
Radioactive Drug Research Committee
Markey Cancer Center (MCC) Protocol Review
and Monitoring Committee (PRMC)
Graduate Medical Education Committee (GME)
Office of Medical Education (OME)
Additional Information
Institutional Biosafety Committee (IBC)--Attach required IBC
materials
Radiation Safety Committee (RSC)-- For applicability, see
instructions and/or upload form [WORD] [PDF]
Radioactive Drug Research Committee (RDRC)--information
Markey Cancer Center (MCC) Protocol Review and Monitoring
Committee (PRMC)**--Attach MCC PRMC materials, if any, per
instructions
See requirement of Office of Medical Education (OME)
See requirement of Graduate Medical Education Committee
(GME)
Attachments 
** If you are proposing a study involving cancer research, be sure to have "Cancer Research" marked in the E-
IRB "Research Attributes" section. If your study involves cancer research, ORI will provide a copy of your research
protocol to the Markey Cancer Center (MCC) Protocol Review and Monitoring Committee (PRMC). The MCC PRMC is
responsible for determining whether the study meets the National Cancer Institute (NCI) definition of a clinical trial and for
issuing documentation to you (the investigator) which confirms either that PRMC approval has been obtained or that PRC
review is not required. Your IRB application will be processed and reviewed independently from the PRMC review.
Section 15 Page 1 of 1
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ADDITIONAL INFORMATION/MATERIALS
Do you want specific information inserted into your approval letter?
Yes
No
Approval Letter Details (e.g., serial #):
Submission Description: If you wish to have specific details included in your approval letter (e.g., serial #, internal tracking
identifier, etc…), type in the box below exactly what you wish to see on the approval letter. What you type will automatically appear
at the top of all approval letters, identical to how you typed it, until it is changed by you (Hint: don't include instructions or questions
to ORI staff as those will appear in your approval letter). If these details need to be changed as a result of revisions,
continuation review, or modifications to the application, you are responsible for updating the content of the field
below accordingly.
Please note: All of the documents have received extensive input from
the clinical PI and his team as well as from our CRO partner (Covance
Inc). Additionally, they have been informally reviewed by several malaria
focused physician scientists from various countries around the world.
As part of the Peruvian regulations, these documents are currently
being reviewed by the Peruvian ethics committee Comité Institucional
de Bioética (CIB) de VÍA LIBRE, which is acting as a local IRB. After
their approval, we will apply to the Peruvian Ministry of Health for
approval as well as through the Perurvian National Institute of Health
(General Office of Research and Technology Transfer, OGITT), the
regulatory agency for Peruvian clinical trials. Pending the outcome of
these submissions and the UK IRB decision, we will be able to apply
for our import license and hope to start the trial in early November. Due
to the seasonality of Malaria, it is critical that we are actively recruiting
patients during the rainy season (November - April).
On May 14th we received initial feedback from the Peruvian ethics
committee Comité Institucional de Bioética (CIB) de VÍA LIBRE
(attached below). These initial changes are included in this submission
and have been resubmitted for final review by the Peruvian committee
later this month. 
Serial #000
Protocol Version 1.0
Consent Version 1.0
Investigator Brochure Version 1.0 
Study Ads dated April 20,2020
Protocol/Product Attachments - For each item checked, please attach the corresponding material.
Detailed protocol
Dept. of Health & Human Services (DHHS) approved protocol (such as NIH sponsored Cooperative Group Clinical Trial)
Drug Documentation (e.g., Investigator Brochure; approved labeling; publication; FDA correspondence, etc.)
Device Documentation (e.g., Manufacturer information; patient information packet; approved labeling; FDA correspondence,
etc.)
Other Documents
Protocol/Product Attachments
Attach Type
File Name
AddInfoProduct Eisai Label Text_United States_en_es.docx
AddInfoProduct 300mg capsule CofA L0700840_ES-LA.docx
AddInfoProduct 20200501_SJ733_Investigators_Brochure_en.docx
AddInfoProduct 20200501_SJ733_Investigators Brochure_es.docx
AddInfoProduct PNAS_SJ733.pdf
AddInfoProduct 2020_LancetID.pdf
AddInfoProduct 300mg capsule CofA L0700840.pdf
AddInfoProduct Tybost latest product label.pdf
Section 16 Page 1 of 2
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AddInfoProduct Tybost latest product label(es)-proofread.pdf
AddInfoProduct 20200615_Patient_Borchure_ES_EN_v2.pdf
AddInfoProtocol EC comment letter_SJ733-2001 Dr. Elmer Llanos_14May20(en).pdf
AddInfoProtocol 20200406_SJ733_Clinical_Protocol_V1.0_en.docx
AddInfoProtocol 20200430_SJ733_Clinical_Protocol_V1.0_es.docx
NOTE: Instructions for Dept. of Health & Human Services (DHHS)-approved protocol]
If you have password protected documents, that feature should be disabled prior to uploading to ensure access
for IRB review.
Additional Materials:
If you have other materials you would like to include in your application for the IRB’s consideration, please attach using the Attachments
button below.
[To view what materials are currently attached to your application, go to “Application Links” in the menu bar on the left and click “All
Attachments”.]
Attachments
Attach Type
File Name
AdditionInfoConsiderations 20200430_Peru_SJ733-2001_Insurance.pdf
AdditionInfoConsiderations 20200430_Peru_SJ733-2001_Insurance_Policy_es.PDF
AdditionInfoConsiderations 20200414_SJ733 Patient_Alert_Card_en.docx
AdditionInfoConsiderations 20200414_SJ733 Patient_Alert_Card_es.docx
AdditionInfoConsiderations 20200430_SJ733_Clinical_Protocol_V1.0_Cert_of_Translation.pdf
AdditionInfoConsiderations 20200501_Patient_Brochure_Cert_of_Translation.pdf
AdditionInfoConsiderations 20200501_Phase2a_Main_Consent_Cert_of_Translation.pdf
AdditionInfoConsiderations 20200501_SJ733_Investigators_Brochure_Cert_of_Translation.pdf
AdditionInfoConsiderations 20200501_Phase2a_PK_Consent_Cert_of_Translation.pdf
AdditionInfoConsiderations EC GCP letter_16Jun20.pdf
AdditionInfoConsiderations EC membership list 16Jun20.pdf
AdditionInfoConsiderations Initial EC approval letter_16Jun20.pdf
AdditionInfoConsiderations Institutional approval letter_09Jun20.pdf
AdditionInfoConsiderations Main ICF SSV1.0_stamped 16Jun20.pdf
AdditionInfoConsiderations PAC V1.0_stamped 16Jun16.pdf
AdditionInfoConsiderations patient Brochure_Stamped 16Jun16.pdf
AdditionInfoConsiderations PK ICF V1.0_stamped 16Jun16.pdf
AdditionInfoConsiderations IRB Requested Revisions.pdf
AdditionInfoConsiderations 20201009_SJ733-2001_INS_Submission_full.pdf
Section 16 Page 2 of 2
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SIGNATURES (ASSURANCES)
On all IRB applications there is a requirement for additional assurances by a Department Chairperson (or equivalent) [hereafter referred
to as "Department Authorization" (DA)], and when applicable, a Faculty Advisor (FA) (or equivalent), which signifies the acceptance of
certain responsibilities and that the science is meritorious and deserving of conduct in humans. Note: the individual assigned as DA
should not also be listed in the Study Personnel section, the individual assigned as FA should be listed in the Study Personnel section.
For a list of responsibilities reflected by signing the Assurance Statement, download the guidance document "What does the
Department Chairperson’s Assurance Statement on the IRB application mean? [PDF]" 
Required Signatures:
First
Name
Last
Name
Role
Department
Date
Signed
 
Joseph
Chappell
Department
Authorization
Pharmaceutical
Sciences
06/22/2020
11:47 AM
View/Sign
Rodney
Guy
Principal
Investigator
Pharmaceutical
Sciences
06/22/2020
11:21 AM
View/Sign
Department Authorization
 This is to certify that I have reviewed this research protocol and that I attest to the scientific validity and importance of
this study; to the qualifications of the investigator(s) to conduct the project and their time available for the project; that
facilities, equipment, and personnel are adequate to conduct the research; and that continued guidance will be provided
as appropriate. When the principal investigator assumes a sponsor function, the investigator has been notified of the
additional regulatory requirements of the sponsor and by signing the principal investigator Assurance Statement, confirms
he/she can comply with them.
*If the Principal Investigator is also the Chairperson of the department, the Vice Chairperson or equivalent should complete
the "Department Authorization".
**IF APPLICABLE FOR RELIANCE: I attest that the principal investigator has been notified of the regulatory requirements of
both the Reviewing and Relying IRBs, according to the information provided in the E-IRB application. The attached Reliance
Assurance Statement, signed by the principal investigator, confirms that he/she can comply with both sets of IRB
requirements.
Principal Investigator’s Assurance Statement
I understand the University of Kentucky's policies concerning research involving human subjects and I agree:
1. To comply with all IRB policies, decisions, conditions, and requirements;
2. To accept responsibility for the scientific and ethical conduct of this research study;
3. To obtain prior approval from the Institutional Review Board before amending or altering the research protocol or
implementing changes in the approved consent/assent form;
4. To report to the IRB in accord with IRB/IBC policy, any adverse event(s) and/or unanticipated problem(s) involving risks to
subjects;
5. To complete, on request by the IRB for Full and Expedited studies, the Continuation/Final Review Forms;
6. To notify the Office of Sponsored Projects Administration (OSPA) and/or the IRB (when applicable) of the development of
any financial interest not already disclosed;
7. Each individual listed as study personnel in this application has received the mandatory human research protections
education (e.g., CITI);
8. Each individual listed as study personnel in this application possesses the necessary experience for conducting research
activities in the role described for this research study.
9. To recognize and accept additional regulatory responsibilities if serving as both a sponsor and investigator for FDA
regulated research.
Furthermore, by checking this box, I also attest that:
Section 17 Page 1 of 2
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I have appropriate facilities and resources for conducting the study;
I am aware of and take full responsibility for the accuracy of all materials submitted to the IRB for review;
If applying for an exemption, I also certify that the only involvement of human subjects in this research study will be in the
categories specified in the Protocol Type: Exemption Categories section.
If applying for an Abbreviated Application (AA) to rely on an external IRB, I understand that certain items above (1, 3, 4, 7-8)
may not apply, or may be altered due to external institutional/IRB policies. I document my agreement with the Principal
Investigator Reliance Assurance Statement by digitally signing this application.
*You will be able to "sign" your assurance after you have sent your application for signatures (use Submission section). Please notify the
personnel required for signing your IRB application after sending for signatures. Once all signatures have been recorded, you will need
to return to this section to submit your application to ORI. 
Section 17 Page 2 of 2
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SUBMISSION INFORMATION
Each Section/Subsection in the menu on the left must have a checkmark beside it (except this Submission section) indicating the
Section/Subsection has been completed; otherwise your submission for IRB review and approval will not be able to be sent to the
Office of Research Integrity/IRB.
Please remember to update, when applicable, the Approval Letter Details text box under the Additional Information section to ensure
verbiage you want on your approval letter is accurate.
If your materials require review at a convened IRB meeting which you will be asked to attend, it will be scheduled on the next available
agenda and a message will be forthcoming to notify you of the date.
If you are making a change to an attachment, you need to delete the attachment, upload a highlighted version that contains the changes
(use Document Type of "Highlighted Changes"), and a version that contains the changes without any highlights (use the appropriate
Document Type for the item(s)). Do not delete approved attachments that are still in use.
Your protocol has been submitted.
Section 18 Page 1 of 1
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Research Product: (+)-SJ000557733 (SJ733) and cobicistat 
Study #: SJ733-2001 
MAIN INFORMED CONSENT PERU VERSION 1.0 April 27, 2020.  
MAIN INFORMED CONSENT PERU_DR. ELMER LLANOS_VERSION 1.0, May 28, 2020. Translated to 
Spanish on June 4, 2020. 
CONFIDENTIAL 
Page 1 of 15 
MAIN INFORMED CONSENT 
TITLE: 
An Open Label Phase 2a Study to Assess the Efficacy, Safety, 
Tolerability and Pharmacokinetics of (+)-SJ000557733 (SJ733), 
with or without Combination with Cobicistat, in Adult Patients with 
Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria 
Mono-Infection over a 42 Day Period 
PROTOCOL NO.: 
SJ733-2001 
SPONSOR: 
Rodney Kiplin Guy 
789 South Limestone  
Lexington, KY 40536 
United States of America (USA) 
LEGAL REPRESENTATIVE: 
Covance Perú Services S.A.  
Av. De La Floresta 497, Int. 201, 
Edificio Parque Las Lomas,  
San Borja, ZIP 15038, Perú 
INVESTIGATOR: 
Dr. Elmer Alejandro Llanos-Cuentas 
Telephone: 994 273 050 
E-mail: alejandro.llanos.c@upch.pe
SITE NAME: 
Asociación Civil Selva Amazónica (ACSA) 
Centro de Investigacion: Asociación Civil Selva Amazónica. RCI -
287 
Urb. Jardín N.° 27 (altura cuadra 4 Av. Fanning) 
Iquitos, Loreto – Perú 
IRB NAME: 
Comité Institucional de Bioética (CIB) de VÍA LIBRE 
Jr. Paraguay 490, Cercado de Lima, Lima, Perú 
REGULATORY AUTHORITY: 
Instituto Nacional de Salud 
IRB Approval
11/2/2020
IRB # 53333
IRB1


Research Product: (+)-SJ000557733 (SJ733) and cobicistat 
Study #: SJ733-2001 
MAIN INFORMED CONSENT PERU VERSION 1.0 April 27, 2020.  
MAIN INFORMED CONSENT PERU_DR. ELMER LLANOS_VERSION 1.0, May 28, 2020. Translated to 
Spanish on June 4, 2020. 
CONFIDENTIAL 
Page 2 of 15 
PATIENT  INFORMATION FOR AN OPEN LABEL PHASE 2A STUDY TO ASSESS THE EFFICACY, 
SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF (+)-SJ000557733 (SJ733), WITH OR 
WITHOUT COMBINATION WITH COBICISTAT, IN ADULT PATIENTS WITH ACUTE, 
UNCOMPLICATED PLASMODIUM FALCIPARUM OR VIVAX MALARIA MONO-INFECTION OVER A 
42 DAY PERIOD 
INTRODUCTION 
We are inviting you to volunteer for an experimental research study authorized by the Comité Institucional 
de Bioética VÍA LIBRE (CIB) and Instituto Nacional de Salud (INS). The study will test a newly discovered 
research product called SJ733 with or without cobicistat as a new treatment for malaria.  Cobicistat blocks 
the body’s ability to metabolize (break-down) other medicines. The study will test SJ733 with or without 
cobicistat to see if SJ733 with cobicistat is safe and if cobicistat can increase the amount of SJ733 that 
remains in the body and therefore improve the effect that SJ733 may have on malaria. 
We are asking you to participate because you have been diagnosed with malaria. To assure your 
voluntary participation without being obligated by someone (coercion), please take the time to carefully 
understand the information about the two research products SJ733 and cobicistat as well as the study. 
The team will answer any questions you have. The contact information for the investigator in charge of 
the study is given below.   
It is very important that you fully understand the study before agreeing to participate.  
Rodney Kiplin Guy is supporting this research by providing funding, SJ733, and cobicistat for use in this 
study and is sometimes referred to as “Sponsor”. The study doctor will receive payment/compensation for 
conducting this study. 
WHAT IS THE STUDY ABOUT AND HOW LONG WILL IT LAST?  
This study will help us learn more information about whether SJ733 (research product) when given with or 
without cobicistat (research product) is safe and can effectively treat malaria. SJ733 is new and not 
approved by the United States Food and Drug Administration (FDA) or the autoridad Nacional de 
Productos Farmacéuticos, Dispositivos médicos y productos sanitarios (ANM; formerly DIGEMID). 
Cobicistat is not approved by the FDA nor by the ANM for the treatment of malaria.  Your participation in 
this research will last about 42 days. 
WHAT ARE KEY REASONS YOU MIGHT CHOOSE TO VOLUNTEER FOR THIS STUDY? 
The results of the study will help to see if SJ733 with or without cobicistat can be a new treatment for 
malaria. SJ733 may help you with your malaria but there is no guarantee it will work. If SJ733 with or 
without cobicistat is shown to be safe and effective for the treatment of malaria, it may help other patients 
with malaria that cannot be cured with the currently available drugs. 
WHAT ARE KEY REASONS YOU MIGHT CHOOSE NOT TO VOLUNTEER FOR THIS STUDY? 
There are possible side effects of SJ733 including nausea (feeling sick to the stomach), dizziness, loss of 
appetite, vomiting, diarrhea, fever, headaches, fatigue (tiredness or low energy). These effects have been 
mild to moderate and have not stopped previous volunteers from taking SJ733. In dogs, large amounts of 
SJ733 affected the way blood cells carry oxygen to the body. The effects went away after SJ733 was 
stopped.  This has never been seen in humans. Cobicistat can cause jaundice (yellowing of the skin 
and/or whites of the eyes) and skin rash. It can also decrease how well your kidneys work. We will closely 
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monitor your health during the study.  There is more information about the risks of the study later in this 
consent. If you are pregnant or nursing, you cannot participate.  You or your partner should not become 
pregnant during this study.  The complete study will take a lot of your time and you will need to remain in 
Iquitos for five consecutive days and return to Iquitos for some follow-up visits.   
DO YOU HAVE TO TAKE PART IN THE STUDY? 
You do not have to take part in the study.  If you take part in the study, it should be because you want to 
volunteer. You will not lose any services, benefits or rights you would normally have if you choose not to 
volunteer.  If you do not participate in the study, you will receive the standard treatment for malaria in 
Peru.  
WHAT IF YOU HAVE QUESTIONS, SUGGESTIONS OR CONCERNS? 
If you have questions, suggestions, or concerns regarding this study or you want to withdraw from the 
study contact Elmer Alejandro Llanos-Cuentas MD, Ph.D. at 994 273 050 or 
alejandro.llanos.c@upch.pe.
If you have any concerns or questions about your rights as a volunteer in this research, contact staff at 
the Vía Libre Ethics Committee at 511 203-9900 ext. 131. 
DETAILED INFORMED CONSENT 
1. STUDY PURPOSE
People get malaria after a bite from a mosquito infected with the malaria parasite.  The malaria first infects 
the liver and then the blood. The most common symptoms of malaria (fever, chills, general discomfort, 
headaches, muscle aches) are caused by the infected blood cells bursting.  Malaria can make someone 
very sick and even cause death if not treated with medicine.   
The goal of this study is to test if a newly discovered research product called SJ733 taken with or without 
cobicistat is safe and if it kills the parasites that cause malaria. Cobicistat blocks the body’s ability to 
metabolize (break-down) other medicines. The study will test SJ733 with or without cobicistat to see if 
SJ733 with cobicistat is safe and if cobicistat can increase the amount of SJ733 that remains in the body 
and therefore improve the effect that SJ733 may have on malaria. The study will also determine how much 
SJ733 a patient must take to work its best.  
SJ733 is still being studied and is not yet approved to treat malaria by the United States Food and Drug 
Administration (FDA), autoridad Nacional de Productos Farmacéuticos, Dispositivos médicos y productos 
sanitarios (ANM; formerly DIGEMID), or any other regulatory agency for public use.  Cobicistat is approved 
by the ANM and FDA only when combined with several human immunodeficiency virus (HIV) drugs to 
increase the amount of those HIV drugs that remain in the body. Cobicistat is not approved by the FDA, 
ANM, or any other regulatory agency for the treatment of Malaria. 
2.
WILL YOU BENEFIT FROM PARTICIPATING IN THIS STUDY?
We do not know if you will get any direct benefit from participating in this study. SJ733 with or without 
cobicistat may cure your malaria.  The results of the study will help to find new treatments for malaria. If 
SJ733 with or without cobicistat is safe and cures malaria, this research product could be a great help for 
other malaria patients.  Malaria is becoming resistant to current standard treatments so the number of 
patients that are not able to be cured is rising worldwide. 
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3. WHERE IS THE STUDY GOING TO TAKE PLACE AND HOW LONG WILL IT LAST?
This study will take place in Iquitos, Peru at the Asociación Civil Selva Amazónica (ACSA). The complete 
study will last about 42 days. This study is estimated to include 20 to 60 research subjects (participants) 
and will be carried out only in Peru. 
4.
HOW MUCH WILL IT COST YOU TO PARTICIPATE?
You will not be charged for any services specifically required for this study. The Sponsor will cover the cost 
of the research products, all the associated tests, hospitalization, clinical visits (including transportation 
costs and food), and any hotel bills (if required) for this study. 
5.
WILL YOU RECEIVE ANY REWARDS FOR PARTICIPATING IN THIS STUDY?
You will not receive any payment for your participation in the study. However, you will receive up to S/. 85 
soles for each day that you miss work (lost wages) to go to the site for participating in the study, either for 
admission to the study, receiving treatment and/ or follow-up appointments. In addition, you will be 
reimbursed up to a maximum of S/. 50 soles per visit for any transportation expenses, communication and 
food expenses incurred for the visits related to the study. 
6. ALTERNATIVE TREATMENTS
Your alternative is to not participate in the study and receive treatment according to the malaria regulations 
of Peru. Your study physician will explain to you what the alternative treatments are and discuss with you 
their risks and benefits. 
7.
ARE THERE REASONS WHY YOU DO NOT QUALIFY FOR THIS STUDY?
You should not take part in this study if: 
•
you are not willing or able to comply with the study requirements
•
you are unable to give informed consent
•
you are under the age of 18
•
you are over the age of 70
•
you weigh less than 45 kg
•
you weigh more than 90 kg
•
you are severely sick including severe vomiting or diarrhea, either because of malaria or another
disease
•
you are pregnant or breast feeding
•
you are unable to remain sexually abstinent or use methods to prevent pregnancy (oral/injectable
contraceptives and barrier contraception, e.g. condom)
•
you are unable to swallow pills
•
you have laboratory tests that do not meet the requirements to remain in the study
•
you are unable to remain in Iquitos for at least five days and unable to attend all study visits
•
you are an employee under the direct supervision of the investigators or study staff
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•
you have volunteered for another study with a drug that is not allowed in this study
•
your malaria is caused by more than one species of parasite
•
you are taking other medications that are not allowed in this study
8.
PATIENT RESPONSIBILITIES
To monitor your health, the study will be under the direct supervision of the study physician and will be 
conducted by trained personnel. Please provide all information about your current and past health (medical) 
history at the screening visit. We need this information to protect your health. 
Your responsibilities as a study patient/participant are the following: 
•
Provide honest and complete information about your medical history and current medical conditions
•
Notify the study physician about any other medications or herbs/home remedies that you have taken,
are taking, or plan to take. 
•
Notify the study physician of any other research studies you have been in during the last three
months, are currently in, or plan to be in. 
•
Notify the study physician if you have had malaria in the last three months and of any other
treatments you have received or are receiving. 
•
Notify the study physician about any problems you have during the study.
•
Take the research product as indicated by the study physician and study personnel.
•
Remain at the clinic as required by the study.
•
Immediately notify study personnel about any side effects that you have, including changes that you
may not consider important. 
•
Follow the instructions and come back for your scheduled visits.
9. WHAT WILL YOU BE ASKED TO DO?
If you choose to participate, you will sign this informed consent form in two copies agreeing to become a 
research subject (participant). Next, you will have blood samples drawn (about 24 mL or 5 teaspoons) and 
be asked for a urine sample for routine laboratory tests and to identify the type of malaria you have (there 
are more than one). You will be asked a series of questions about your medical history. You will have a 
physical exam and vital signs taken. We will test how your heart is working with an electrocardiogram 
(ECG).  
An ECG involves sticking several monitors (which look like small stickers) onto your chest and monitoring 
your heartbeat. The study doctor will determine whether you can participate in the study.   
We do not know the effects of SJ733 during pregnancy. You cannot participate if you are pregnant or 
nursing. For this reason, you or your partner will receive counseling on how to avoid pregnancy.  Also, you 
will receive free contraceptives (birth control) that should be used the entire time that you participate in this 
trial and for 30 days after you stop taking the research product.  
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If you participate, it is important that you take the research product exactly as indicated by the study 
physician, return for all follow-up visits, and comply with all study requirements.   
If your screening tests show that you can continue in the study, you will be given either SJ733 alone or 
together with cobicistat once every day for three days in a row.  You will remain in Iquitos for five days so 
the investigators can see how the treatment works. You will also return to the clinic in Iquitos for nine follow-
up visits on Days 7, 10 or 11, 14, 17 or 18, 21, 24 or 25, 28, 35, and 42. For more details see to the 
Appendix: Study Visits & Procedures. 
Every day that you are at the clinic, you will have a brief physical examination, your vital signs monitored, 
and blood samples drawn.  The blood samples will measure the amount of research product in your blood, 
the number of parasites in your blood, and your general health.  Each blood draw will be about 5 to 35 mL 
of blood (1-7 teaspoons).  During the entire study of 42 days, about 227 mL (46 teaspoons) of blood will be 
drawn. This may sound like a lot, but your body will replace the blood drawn and the amount drawn is 
normal for these types of studies. During this time, you must not take any other medications, unless 
approved by your doctor. For more details, refer to the Appendix: Study Visits & Procedures. 
During the study, if your malaria returns or gets worse, you will be given the standard malaria treatment 
according to the malaria regulations of Peru. You will be asked to continue in the study with the study visits 
as defined in the Appendix: Study Visits & Procedures. 
If you request it, the study physician will provide the study results to you and discuss them with you when 
they are available. 
10. HOW WILL THE RESEARCH PRODUCT BE GIVEN?
All research subjects in the study are given SJ733, as capsules taken by mouth, either alone or in 
combination with cobicistat, as tablets taken by mouth, once every day for three days in a row. You will be 
asked if you have eaten any food within three hours before taking the research product.   
The study is designed to only treat research subjects who have one of the malaria parasite species: vivax 
or falciparum.  
The study may contain up to three groups of research subjects.  The first group of research subjects will be 
given SJ733 as two 300 mg capsules along with one 150 mg tablet of cobicistat and about 250 milliliters of 
water (less than a glass).  
The dosage for the other groups will depend on the results of the first group. The study physician will explain 
what group you will be part of for the study.   
If the first group is successful, the second group will be given SJ733 as two 300 mg capsules and about 
250 milliliters of water. This group will not be given any cobicistat.  This group will test whether cobicistat is 
needed for SJ733 to have a similar effect as the first group. If the second group is successful, the study will 
be stopped. 
If SJ733 does not work without cobicistat, a third group will be studied who will receive less SJ733 (one 300 
mg capsule) along with one 150 mg tablet of cobicistat along and 250 milliliters of water.  This group will 
test whether a combination of cobicistat with less SJ733 has a similar effect as the first group with the 
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benefit of lower cost and less adverse effects. 
After being admitted to the study, you will remain in Iquitos for five days for treatment and evaluation. 
Standard Malaria Treatment 
If your malaria does not get better within 7 days, you will be given the standard treatment and care according 
to the national regulations for the treatment of malaria in Peru. You will be asked to continue in the study 
and return for all follow-up as defined in the Appendix.  At the end of the study (Day 42) you will receive the 
standard treatment recommended by the national regulations for the treatment of malaria in Peru.  This will 
ensure your malaria is successfully treated. 
11. WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS?
SJ733 
So far, none of the 51 volunteers who have taken SJ733 have reported any serious problems.  In some 
people, SJ733 may have caused nausea, loss of appetite, vomiting, diarrhea, fever and headaches, all of 
which have been from mild to moderate in severity.  During the previous studies, none of the volunteers 
chose to stop taking the research product before the end of the study.  
In dogs, large amounts of SJ733 temporarily decreased how well the dog’s blood cells could carry oxygen 
to the body. Low levels of oxygen can cause the skin to look blue, headaches, and fatigue (tiredness or low 
energy). The effects went away after the dogs stopped taking SJ733. This has not been seen in humans. 
We will closely monitor your oxygen levels and general health during the study.  
It is not yet known if SJ733 is an effective treatment against malaria, there is a risk that your condition may 
not improve or worsen.  If your malaria does not get better within 7 days, you will receive treatment from 
the study physicians following the national regulations for the treatment of malaria in Peru. 
Cobicistat 
Cobicistat can cause jaundice (yellowing of the skin and/or whites of the eyes) and skin rash. It can also 
decrease how well your kidneys work. For this reason, your kidneys will be closely monitored throughout 
the study with blood and urine tests. 
Because cobicistat can increase the number of other drugs in your body, it is very important to provide 
honest and complete information about any other medications or herbs/home remedies that you are taking 
or plan to take. This is very important for your health. 
Blood draw 
At the blood draw site swelling, pain, irritation, or infection may occur.  During the blood draw, some people 
may feel dizzy or faint. To avoid these issues, only qualified and experienced professional will take blood 
samples.  
Electrocardiogram 
The electrocardiogram (ECG) procedure may cause minimal discomfort when the ECG electrodes 
(monitors/stickers) are put on or taken off. 
Risks related to pregnancy/use of contraceptives (birth control) 
We do not know the effects of SJ733 during pregnancy. You cannot participate in the study if you are 
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pregnant or breastfeeding. If you are male, you should not make your partner pregnant, and if you are 
female, you should not become pregnant during your participation in this study. You will receive counseling 
on how to avoid pregnancy.  You will be given free contraceptives that should be used the entire time that 
you participate in this study and for 30 days after your last dose of the research product.  
Prior to participation, female participants must take a pregnancy test to show you are not pregnant. It is 
possible that this test may not detect a pregnancy if you became pregnant too recently. 
Your study physician will ensure that you and/or your partner have access to contraceptives (oral/injectable 
contraceptives and barrier contraceptives, e.g., condoms) that are allowed in this clinical study and are 
convenient for you and/or your partner at no cost to you.  
If you suspect that you may be pregnant (or that your partner may be pregnant) during the study, you 
should notify the study physician immediately.  If you become pregnant during the study, you must tell the 
study doctor about your pregnancy and stop taking all research product immediately.  You will be referred 
to receive appropriate counseling and you will be monitored to observe any possible pregnancy risks 
related to research product.  In addition, your pregnancy will be followed until the outcome.  When you 
give birth, you should inform the study doctor of your baby’s health.  Your baby’s health will be followed 
for at least 1 year after its birthday in order to dismiss the possibility that any problems can be detected. 
As part of the consent, you agree that we will continue collecting information about you at least until the 
birth or termination of the pregnancy. 
Unexpected risks 
There may be problems or side effects from the research products and procedures that we do not yet know 
about. You will be informed about any changes in the way the study will be carried out.  We will tell you of 
any new risks that may make you change your mind about participating in the study. New information will 
be provided to the Ethics Committee and it is possible that you may be asked to review and sign a new 
informed consent. 
12. CAN YOU CHOOSE TO WITHDRAW FROM OR LEAVE THE STUDY EARLY?
Yes, you can choose to leave the study at any time. If you leave the study, you will be treated by the 
study physician following the national regulations for the treatment of malaria in Peru. You will not be 
penalized or treated differently if you decide to stop taking part in the study. If you choose to leave the 
study early, data collected until that point will remain in the study database and may not be removed. 
Also, it is possible that your participation in the study could end at any time without your permission. This 
could occur if you do not follow the instructions given by the study physician or if the study physician 
determines that it is best for you. The study could also be interrupted due to administrative, medical, or 
other reasons as determined by the Sponsor, the Instituto Nacional de Salud –– INS, or other regulatory 
authorities. Once your participation in the study has ended, you will no longer have access to the research 
product or study procedures. 
Your participation in the study will end if: 
•
You decide to withdraw from the study.
•
You show any medical condition that causes you harm or exposes you to unnecessary risks.
•
You show unacceptable/harmful side effects.
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•
There is evidence that your illness has worsened.
•
You become pregnant.
•
You require other medications that are not allowed in this study.
•
You do not comply with scheduled visits/study requirements.
•
The Sponsor, the INS, or other regulatory agency determines that it is necessary to limit or suspend
the study.
Research subjects who are withdrawn (or leave) from the study will be asked to have the same evaluations 
at the time of their withdrawal that they would have had upon completing the study (Day 42). 
13. ARE YOU PARTICIPATING, OR CAN YOU PARTICIPATE, IN ANOTHER RESEARCH STUDY
AT THE SAME TIME AS PARTICIPATING IN THIS ONE?
It is important to let your study physician know if you are participating in another research study. During 
this study, it is important to inform the study physician of any other studies you plan to participate in. 
14. WHAT HAPPENS IF YOU GET HURT OR SICK DURING THE STUDY?
If you believe you are hurt or if you get sick because of something that is caused by the study, you should 
call Elmer Alejandro Llanos-Cuentas at 994 273 050 immediately.  
If you suffer an injury or an adverse effect directly caused by the study drug or any procedure specified in 
the protocol, the Sponsor will pay, or cause others to pay, for your reasonable and necessary medical 
treatment expenses through the CHUBB insurance policy number 530005238 from the beginning until the 
end of the clinical trial. This insurance policy will cover such expenses are paid as long as (a) those 
expenses are not specifically for the symptoms of the condition under study (malaria) or for the expected 
symptoms of your disease, and (b) the cause of the expenses is not due to your failure to follow the 
instructions of Elmer Alejandro Llanos-Cuentas  MD, Ph.D.  The Sponsor will not pay for any wages you 
may lose if you are harmed by the study. 
You, your family, or your legal representative, will receive compensation for medical expenses related to 
a case of disability or death as result of this clinical trial as required by the laws of Peru.  For this to 
happen, the injury, in the opinion of the study doctor and the Sponsor, must have been caused by your 
participation in this study.  No other payments will be provided by the Sponsor. If you would like further 
information about being paid for research-related injuries, please ask the study doctor. 
You do not give up your legal rights by signing this form. 
15. PRIVACY AND CONFIDENTIALITY
By signing this form, you give your consent for the study physician and his team to review your medical 
records gathered during this study. These records, and the information in them, will be obtained and 
processed in electronic form that is used only for investigative purposes related to this study. When we 
write about or share the results from the study, we will remove any personal information and communicate 
about the combined information. Your name and other information that may identify you will be kept private. 
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Your medical records may also be reviewed by the Sponsor or their representatives, the, study team, 
Covance Inc., the Peruvian Ministry of Health through known agencies like the National Health Institute 
(INS); the Director General autoridad Nacional de Productos Farmacéuticos, Dispositivos médicos y 
productos sanitarios  (ANM) (formerly DIGEMID, the United States Food and Drug Administration (FDA), 
the regulatory authorities of other countries, and the Ethics Committee (both Peru and the University of 
Kentucky located in the United States) in order to verify that the study is being carried out in the proper 
manner. These professionals have a commitment to respect the confidentiality of your information and will 
keep your identity and personal information confidential to the extent that the law permits. You should 
understand that by signing this consent form you are granting your permission for this review to happen. If 
the results of the study are published or presented in meetings, you will not be identified. 
Peruvian regulations require that the study physician and/or study personnel protect the privacy of your 
information. We will do everything we can to prevent anyone who is not on the research team from knowing 
that you gave us information, or what that information is. All the information collected will be assigned a 
number code and your identity will remain unknown. Your name and address will not be on the information 
that is obtained about you that comes from the study center, so that you cannot be recognized by it.  Any 
information collected that may be transferred outside of the country to the University of Kentucky will be 
identified only by the number code assigned to your file. Still, absolute confidentiality cannot be guaranteed 
due to the need to share information in the matters previously described. 
Your study physician is responsible for tracking the list of codes that allow your assigned number to be 
connected to your name. This list will be kept at the study site to guarantee that in case of an emergency 
you can be identified and contacted. The list of codes will be kept until the last request for commercialization 
of the research product has been received. 
You have the right to see and photocopy your study-related records if the study physician has this 
information in his possession. By signing this form, you accept the possibility that it may not be possible to 
review some of your study-related records until after the study has been completed, at which time you will 
once again be able to access those records. 
This authorization does not have an expiration date. If you do not revoke (cancel) this authorization, it will 
remain in effect indefinitely. You can cancel this authorization at any time by notifying the study physician 
in writing to address Urb. Jardín N.° 27 (altura cuadra 4 Av. Fanning), Iquitos – Loreto. If you cancel this 
authorization, you will no longer be able to participate in the study and your records will not be shared 
unless it is necessary to preserve the scientific integrity of the study. The information collected before you 
cancel the authorization may still be used and shared with the parties mentioned before. 
At the end of the study worldwide, the study results will be available for the different national regulatory entities, 
including the INS in Peru’s case, who will have the information available in Spanish on this 
webpage http://www.ensayosclinicos-repec.ins.gob.pe. In addition, you may ask the research doctor about the 
study results. You will not be identified in any of these publications or reports. 
Your samples will be processed at the ACSA site laboratory and the Universidad Peruana Cayetano 
Heredia Laboratory. Your samples will be stored for up to five years and then will be destroyed following 
the destruction guidelines of the laboratory 
Your coded samples will be stored for a maximum of five years after the last patient visit for the study at 
Instituto de Medicina Tropical Alexander von Humboldt de la Universidad Peruana Cayetano Heredia 
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located at located in Av. Honorio Delgado 430, San Martín de Porres, Lima, Peru. The storage time allows 
the Sponsor to respond to regulatory questions related to the study and re-check specific protocol 
parameters. After that time, any remaining samples will be destroyed following the guidelines of the 
laboratory. 
16. QUESTIONS/INFORMATION
If you have any questions regarding any part of the study, or in case of harm related to the trial, or if you 
have an adverse reaction, immediately contact: 
Dr. Elmer Alejandro Llanos-Cuentas 
Address: Asociación Civil Selva Amazónica (ACSA) 
Urb. Jardín N.° 27 (altura cuadra 4 Av. Fanning) 
Iquitos - Loreto 
Telephone: 994 273 050 
E-mail: alejandro.llanos.c@upch.pe
You will be informed if during the study there is any other new information that could affect your current 
decision to participate therein. 
If you have any concerns or questions about your rights as a volunteer in this research, contact staff at 
the Comité Institucional de Bioética (CIB) de VÍA LIBRE: 
•
Ethich Committe Chairman: Lic. Karen Cruz Azaña
•
Telephone: (+511) 203-9900 Monday to Friday from 09 am to 18 hrs
•
Address: Jr. Paraguay 490, Cercado de Lima, Lima, Perú
•
e-mail: comitebioetica@vialibre.org.pe
An Ethics Committee is a group of members who are impartial and independent to the medical investigators, 
and their function is overseeing the respect of the dignity and rights of the participants in the design and 
performance of the research projects. 
When you believe your rights are violated or for any complaint, you can contact the National Institute of 
Health (General Office of Research and Technology Transfer, OGITT) regulatory agency for clinical trials, 
through the following telephone number: 748 1111 extension 2191 or by written communication through 
the following e-mail: consultaensayos@ins.gob.pe, or by a formal document submitted through the Filing 
Desk of the institution or by appearing in person to the OGITT at the following address: Capac Yupanqui 
1400, Jesús María, Lima 11. 
53333


Research Product: (+)-SJ000557733 (SJ733) and cobicistat 
Study #: SJ733-2001 
MAIN INFORMED CONSENT PERU VERSION 1.0 April 27, 2020.  
MAIN INFORMED CONSENT PERU_DR. ELMER LLANOS_VERSION 1.0, May 28, 2020. Translated to 
Spanish on June 4, 2020. 
CONFIDENTIAL 
Page 12 of 15 
Appendix: Study Visits & Procedures 
Screen 
Treatment – Remain in Iquitos 
Day 
0 
1 
2 
3 
4 
5 
Informed Consent 
X 
Screening 
X 
Pregnancy Test
X 
Physical Exam 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
X 
X 
Research Product 
Dosing 
X 
X 
X 
PK Blood Samples 
Pre-dose 
0.5, 1, 2, 8 
hours after 
dose 1 
Pre-dose, 
0.5 hours 
after dose 2 
Pre-dose 
0.5, 1, 2, 4, 
8 hours 
after dose 3 
24, 26, 28, 
30, 32 
hours after 
dose 3 
48, 54 hours 
after dose 3 
Safety Blood 
Samples 
X 
X 
X 
X 
X 
PD Blood Samples 
X 
Pre-dose 4, 
8, 12, 16 
hours after 
dose 1 
Pre-dose, 
6, 12, 18 
hours after 
dose 2 
Pre-dose 6, 
12, 18, 24 
hours after 
dose 3 
Additional readings every 
6-12 hours until two 
consecutive negative 
microscopic readings 
Problems or 
Complaints 
X 
X 
X 
X 
X 
X 
Follow-up – Return to clinic for visits 
Day 
7 
10 
or 
11 
14 
17 
or 
18 
21 
24 
or 
25 
28 
35 
42A 
Pregnancy Test
X 
Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
PK Blood Sample 
X 
X 
Safety Blood 
Sample 
X 
X 
X 
X 
X 
PD Blood Sample 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Problems or 
Complaints 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Standard Malaria 
Treatment 
X 
A = Day 42, or day of withdrawal (Note: all Day 42 procedures will be done before standard treatment for 
malaria in Peru is received).  Abbreviations: ECG = Electrocardiogram; PK = Pharmacokinetic (how much 
research product is in the blood); PD = Pharmacodynamic (how many parasites are in the blood). 
53333


Research Product: (+)-SJ000557733 (SJ733) and cobicistat 
Study #: SJ733-2001 
                                                                                    
MAIN INFORMED CONSENT PERU VERSION 1.0 April 27, 2020.  
MAIN INFORMED CONSENT PERU_DR. ELMER LLANOS_VERSION 1.0, May 28, 2020. Translated to 
Spanish on June 4, 2020. 
 
 
CONFIDENTIAL 
Page 13 of 15 
RESEARCH SUBJECT MAIN INFORMED CONSENT FORM 
 
STUDY TITLE: An Open Label Phase 2a Study to Assess the Efficacy, Safety, Tolerability and 
Pharmacokinetics of (+)-SJ000557733 (SJ733), with or without Combination with Cobicistat, in Adult 
Patients with Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-Infection over 
a 42 Day Period 
Protocol number: SJ733-2001 
 
This Informed Consent will be signed in two copies and one of them will be delivered to me [research 
subject] or my [his / her] legal representative. 
The patient should check the following: 
1. I confirm that I have read and understand the study information sheet above.             YES      NO             
2. I confirm that the study has been explained to me and that I have had the opportunity to ask questions 
and enough time to decide if I wish to participate. I know with whom I should communicate in case I have 
any more questions.                                                                      
 
          YES      NO                               
3. I understand that the sections of my medical notes may be reviewed by representatives of the Sponsor, 
University of Kentucky (UK), ethics committees, auditors and national and foreign authorities whenever it 
is relevant for my participation in the study. I give my permission for these persons to have access to my 
medical records.                                                         
 
 
 
         YES      NO                               
4. I agree to the transfer of my personal information, including sensitive information, i.e., race, ethnicity, 
health, date of birth and diagnostic information to UK and regulatory authorities.         YES      NO                        
5. I agree to the storing of my personal information.                                                     YES      NO                                
6. I allow my primary care physician to be notified about my participation in the study. YES      NO                              
7. I agree to form part of the study.                      
 
 
 
       YES      NO                                
 
8. I understand that my participation is voluntary. 
 
                                YES      NO                                 
 
9. I understand that I can withdraw from the study whenever I want, without having to give explanations 
and without this affecting my medical care.                                                                    YES      NO             
 
10. By signing this document, I agree to take part in this clinical trial. I am not renouncing any rights.                                    
YES      NO                        
 
 
53333


Research Product: (+)-SJ000557733 (SJ733) and cobicistat 
Study #: SJ733-2001 
                                                                                    
MAIN INFORMED CONSENT PERU VERSION 1.0 April 27, 2020.  
MAIN INFORMED CONSENT PERU_DR. ELMER LLANOS_VERSION 1.0, May 28, 2020. Translated to 
Spanish on June 4, 2020. 
 
 
CONFIDENTIAL 
Page 14 of 15 
This consent includes the following: 
• Key Information Page 
• Detailed Consent  
 
You will receive a signed and dated copy of this consent form. 
 
 
 
Complete Printed Name of Research Subject  
(or fingerprint if illiterate) 
 
 
 
 
 
Signature of Research Subject  
(if illiterate, please leave blank) 
 
Date of Signature 
(dd / mm / yyyy) 
 
 
 
Research Subject’s DNI Number  
(if illiterate, please leave blank) 
 
Time (am/pm) 
I, the undersigned, legally authorized representative, confirm that I agree to the Research subject taking 
part in this study, as I believe it would be their wish to participate. I understand that if the Research 
subject expresses a different opinion, that they will be withdrawn from the study without loss of any 
benefits to which they would otherwise be entitled. 
 
 
Complete Printed Name of Authorized Representative 
(if applicable - fingerprint if illiterate) 
 
 
 
 
 
Signature of Authorized Representative 
(if applicable - if illiterate, please leave blank) 
 
Date of Signature 
(dd / mm / yyyy) 
 
 
 
Authorized Representative’s DNI Number 
 
Time (am/pm) 
For the Impartial Witness (where applicable) 
• 
I have witnessed the accurate reading of the informed consent form to the research subject 
and he or she has had the opportunity to ask questions. 
• 
I confirm that the research subject has freely given his or her consent. 
 
 
 
 
Complete Printed Name of Impartial Witness 
(if applicable - fingerprint if Illiterate) 
 
 
 
 
 
53333


Research Product: (+)-SJ000557733 (SJ733) and cobicistat 
Study #: SJ733-2001 
                                                                                    
MAIN INFORMED CONSENT PERU VERSION 1.0 April 27, 2020.  
MAIN INFORMED CONSENT PERU_DR. ELMER LLANOS_VERSION 1.0, May 28, 2020. Translated to 
Spanish on June 4, 2020. 
 
 
CONFIDENTIAL 
Page 15 of 15 
 
Signature of Impartial Witness 
(if applicable - if illiterate, please leave blank) 
 
 
 
 
 
Date of Signature 
(dd / mm / yyyy) 
Impartial Witness’ DNI Number 
 
Time (am/pm) 
For the Investigator / study personnel 
I have explained the clinical trial to the research subject, and I have answered all of his or her questions. 
I confirm that he or she understands the information described in this document and has voluntarily 
agreed to take part. 
I, the undersigned, investigator / study personnel, confirm that I have verbally given the necessary 
information about the study, that I answered any additional questions, and that I did not exert any 
pressure on the research subject to participate in the study. 
I declare that I acted in full accordance with the ethical principles described in GCP Guidelines, and other 
national and international legislation in effect. 
 
 
 
 
 
 
Complete Printed Name of Investigator / Study 
Personnel Obtaining Consent  
 
 
 
 
 
 
 
Signature of Investigator / Study Personnel Obtaining 
Consent 
 
 
 
 
 
Date of Signature 
(dd / mm / yyyy) 
Investigator / Study Personnel’s DNI Number 
 
Time (am/pm) 
 
53333


Statistical Analysis Plan 
 
 
1 
 
 
 
 
 
 
 
 
Statistical Analysis Plan 
 
An Open Label Phase 2a Study to Assess the Efficacy, Safety, 
Tolerability, and Pharmacokinetics of (+)-SJ000557733 (SJ733) with 
or without Combination with Cobicistat in Adult Patients with 
Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria 
Mono-Infection over a 42 Day Period 
 
 
 
 
 
Date: 
11/30/2022 
Project Name (PI/Sponsor): 
SJ733 (Guy) 
IRB Number: 
53333 
Version: 
 
 
 
  1.8


Statistical Analysis Plan 
 
 
2 
 
Table of Contents 
List of Abbreviations and Definitions of Terms ........................................................................................ 3 
Introduction .................................................................................................................................................. 5 
1. 
Project Objectives ................................................................................................................................ 5 
2. 
Project Description .............................................................................................................................. 6 
Background ................................................................................................................................................................. 6 
Study Design ............................................................................................................................................................... 6 
Study Population ......................................................................................................................................................... 8 
3. 
Data Elements....................................................................................................................................... 9 
Endpoints .................................................................................................................................................................... 9 
Exploratory Endpoints: ............................................................................................................................................. 10 
Data Sources ............................................................................................................................................................. 10 
Creation of Analysis Datasets and Analytic Data Handling ..................................................................................... 11 
4. 
Statistical Methods ............................................................................................................................. 11 
General Approach ..................................................................................................................................................... 12 
Primary Analysis (Efficacy) ..................................................................................................................................... 12 
Exploratory Analysis ................................................................................................................................................ 13 
Safety Analysis ......................................................................................................................................................... 13 
Planned Interim Analyses ......................................................................................................................................... 14 
Strategies to Minimize Bias ...................................................................................................................................... 14 
Sample Size Justification .......................................................................................................................................... 14 
5. 
Planned Tables, Listings, and Figures. ............................................................................................ 15 
6. 
Planned Start and End of Analysis................................................................................................... 16 
7. 
Version Changes................................................................................................................................. 17 
8. 
Document Approval ........................................................................................................................... 17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
 
3 
List of Abbreviations and Definitions of Terms 
 
Abbreviation 
Definition 
ACPR 
Adequate clinical and parasitological response 
ACT 
Artemisinin-based combination therapies 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
ASTAS 
Aspartate aminotransferaseArtesunate 
AUCAST 
Area under the plasma concentration-time curveAspartate 
aminotransferase 
AUCinfAUC 
The area under the plasma (or serum or blood) concentration-time 
curve from time zero to infinityArea under the plasma 
concentration-time curve 
AUClastAUCinf 
The area under the plasma (or serum or blood) concentration-time 
curve from time zero to the time of the last quantifiable 
concentrationThe area under the plasma (or serum or blood) 
concentration-time curve from time zero to infinity 
AUClast 
The area under the plasma (or serum or blood) concentration-time 
curve from time zero to the time of the last quantifiable 
concentration 
CI 
Confidence interval 
DDT 
Data Definition Tables 
Cmax 
Maximum measured plasma concentration 
DR SAE 
Drug-Related Serious Adverse Event 
DMC 
Data Monitoring Committee 
DMID 
Division of Microbiology and Infectious Diseases, NIAID, NIH, 
DHHS 
ECG 
Electrocardiogram 
eDISH  
Evaluation of Drug-Induced Serious Hepatotoxicity 
F 
Bioavailability of a compound 
Hb 
Hemoglobin 
IBSM 
Induced Blood Stage Malaria 
IRB 
Institutional Review Board 
L 
Liter 
LDH 
Lactate dehydrogenase 
LFT 
Liver function test 
LOD 
Limit of Detection 
MEC 
Minimum Effective Concentration 
MedDRA 
Medical Dictionary for Regulatory Activities 


Statistical Analysis Plan 
 
 
4 
MIC 
Minimum Inhibitory Concentration 
n 
Total number observations in the sample 
ND 
Not detectable 
P. falciparum 
Plasmodium falciparum 
P. vivax 
Plasmodium vivax 
PC100 
Time to total microscopic clearance of asexual parasites 
PC50 
Time to microscopic 50% reduction of asexual parasites 
PC99 
Time to microscopic 99% reduction of asexual parasites 
PCR 
Polymerase Chain Reaction 
PCT 
Parasite Clearance Time 
PD 
Pharmacodynamics(s) 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
PR 
PR interval (ECG)###  
PRR 
Parasite Reduction Rate 
qPCR 
Quantitative Polymerase Chain Reaction 
QTcB 
QT interval corrected with Bazett’s formula 
QTcF 
QT interval corrected with Fridericia's formula 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAP 
Statistical Analysis Plan 
SAS 
SAS® (Statistical Analysis Software) 
SD 
Standard deviation 
SGPT 
Serum glutamic-pyruvic transaminase 
SGOT 
Serum glutamic-oxaloacetic transaminase 
SJ733 
(+)-SJ000557733 (study drug) 
SRT 
Safety Review Team 
t1/2 
Half-life 
Tmax 
Time after drug administration when maximum concentration is 
reached 
ULN 
Upper Limit of Normal 


Statistical Analysis Plan 
 
 
5 
Introduction 
 
This statistical analysis plan (SAP) outlines the planned analysis for Project SJ733-2001, entitled 
An Open Label Phase 2a Study to Assess the Efficacy, Safety, Tolerability, and 
Pharmacokinetics of (+)-SJ000557733 (SJ733) with or without Combination with Cobicistat in 
Adult Patients with Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-
Infection over a 42 Day Period. This SAP applies to the project as of  11/04/2022 (Version 1.8) 
and provides a description of the data analysis methods. 
 
1. Project Objectives 
 
Primary: 
1) To determine the efficacy of SJ733 with or without combination with the 
pharmacoenhancer cobicistat, given once per day for three-consecutive days by 
examining parasitemia 14-days after initiation of therapy for the treatment of 
uncomplicated P. vivax or P. falciparum malaria monoinfection. 
 
2) To evaluate the safety and tolerability of SJ733, with or without combination with the 
pharmacoenhancer cobicistat, given once per day for three-consecutive days in patients 
with P. falciparum and P. vivax malaria infection. 
 
Secondary: 
1) To assess the effect of the proposed three-day therapy on the signs and symptoms of P. 
vivax or P. falciparum malaria infection up to Day 42 
2) To assess the effect of the proposed three-day therapy on treatment outcomes in patients 
with P. vivax or P. falciparum malaria infection at Days 28, 35, and 42 
3) To describe parasite clearance kinetics in patients with P. vivax or P. falciparum malaria 
infection 
4) To describe the pharmacokinetics of SJ733 and its primary metabolite SJ506 during the 
three-day dosing period and for 7 additional days in patients with P. falciparum and P. 
vivax malaria infection. 
 
Exploratory: 
1) To assess the effect of the proposed three-day therapy on PCR adjusted outcomes in 
patients with P. vivax or P. falciparum malaria infection: 
a. With PCR-adjustment at Days 7, 14, 28, 35, and 42 (P. falciparum only) 
b. PCR adjusted rates of recurrence (P. vivax or P. falciparum), up to Day 42. 


Statistical Analysis Plan 
 
 
6 
 
2. Project Description 
 
Background 
 
SJ733 is a new antimalarial drug candidate that has undergone single ascending dose, 
pharmacoboosted single ascending dose (pharmacoenhancement with cobicistat), food 
effect single dose, and multiple ascending dose Phase 1 studies in healthy volunteers to 
demonstrate safety, tolerability, and its pharmacokinetic profile. SJ733 has also been 
tested in a two-cohort single dose, Phase 1b, human Induced Blood Stage Malaria 
(IBSM) challenge study. Overall, SJ733’s excellent tolerability and safety profile, 
combined with its rapid antiparasitic effect, support its candidacy as an antimalarial 
therapy. The Phase 1 clinical data and PK/PD models suggest that SJ733 is most likely 
to be curative as a 3-daily-dose pharmacoenhanced therapy, due to its moderately rapid 
clearance. 
 
The present proof of concept Phase 2a trial will be an adaptive, open label study to 
examine the antimalarial efficacy, safety, and tolerability of SJ733 in adult patients with 
uncomplicated P. vivax or P. falciparum blood-stage malaria monoinfection. SJ733 will 
be administered orally once every day for three consecutive days, with or without a fixed 
dose of the pharmacoenhancer cobicistat, to determine if pharmacoenhancement is 
required, and if significant improvements in drug efficacy are seen at higher total 
exposures of SJ733. Success will be defined independently for each treatment arm at Day 
14 as: 1) the absence of any repeated drug-related serious adverse event; and 2) crude 
ACPR ≥ 80% (equivalent to ≤ 20% recurrence). Crude ACPR is defined as the absence of 
microscopically determined parasitemia (thick smear), irrespective of axillary 
temperature, in patients who did not previously meet any of the criteria of early treatment 
failure, late clinical failure, or late parasitological failure. Additional aims are to 
characterize the antiparasitic activity, safety, tolerability, and pharmacokinetics of SJ733 
over the period of 42 days. The results of this trial will help identify effective, well- 
tolerated doses for investigation in combination with a partner drug within a Phase 2b 
clinical study. 
 
Study Design 
 
This will be a proof-of-concept Phase 2a, adaptive, open label study to examine the 
efficacy of SJ733 given once per day for three-consecutive days, with or without 
combination with the pharmacoenhancer cobicistat, in uncomplicated P. vivax or P. 
falciparum blood-stage malaria monoinfection in adult patients in Peru. Success will be 
defined independently for each treatment arm at Day 14 as: 1) the absence of any 
repeated drug-related serious adverse event; and 2) crude ACPR ≥ 80% (equivalent to ≤ 
20% recurrence). Crude adequate clinical and parasitological response (ACPR) is defined 
as the absence of microscopically determined parasitemia (thick smear), irrespective of 
axillary temperature, in patients who did not previously meet any of the criteria of early 
treatment failure, late clinical failure, or late parasitological failure. 
Patients will be recruited as per Figure 1 into one of two treatment arms: 
1. 
Arm A: P. falciparum malaria, or 
2. 
Arm B: P. vivax malaria 


Statistical Analysis Plan 
 
 
7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1. Treatment scheme for cohorts 1-3. Each cohort contains two treatment arms, P. 
falciparum (a) and P. vivax (b). Cohort progression will be managed independently for each 
treatment arm. Interim analysis will determine whether the data for a given treatment arm 
meets the success criteria, is inconclusive, or meets the failure criteria. Crude adequate clinical 
and parasitological response (ACPR) is defined as the absence of microscopically determined 
parasitemia (thick smear), irrespective of axillary temperature, in patients who did not 
previously meet any of the criteria of early treatment failure, late clinical failure, or late 
parasitological failure. Success is defined at Day 14 as: 1) the absence of any repeated drug- 
related serious adverse event (DR SAE); and 2) crude ACPR ≥ 80% (equivalent to ≤ 20% 
recurrence). An inconclusive result is defined at Day 14 as: 1) the absence of any repeated DR 
SAE; and 2) ACPR between 60-80%. Failure is defined as: 1) the detection of any repeated 
DR SAE; or 2) ACPR < 60%. 
 
A minimum of one cohort containing two treatment arms (20 patients; 10 patients per 
arm) will be investigated with a maximum of 3 cohorts (60 patients; 3 dosing regimens; 2 
arms; 10 patients per arm) being tested as shown in Figure 1.  The starting dosing 
regimen for the first P. vivax or P. falciparum cohorts will be three consecutive daily 
doses of the combination of SJ733 (600 mg) and cobicistat (150 mg). Based on the results 
from completed Phase 1a/1b studies, this dose is expected to be well-tolerated and show 
complete clearance of parasites on Day 7 as determined by microscopy (thick blood 
smear) and a  20% recrudescence rate as assessed by microscopy on Day 14. 
If the data from the first cohorts of P. falciparum (cohort 1A) and P. vivax (cohort 1B) 
respectively meet the success criteria, two other dosing regimens, expected to yield 
reduced total exposures of SJ733, may be investigated. Each is expected to be 
efficacious. If data from the first cohorts are inconclusive, an adaptation will be triggered 
to use the same dosing regimen for a larger number of patients in order to improve 
statistical power and more accurately classify a potential failure. An inconclusive result 
will be defined at Day 14 as: 1) the absence of any repeated drug-related SAE; and 2) 
crude ACPR between 60-80% (equivalent to 20-40% recurrence). If data from the first 
cohorts result in failure, the trial will be stopped. Failure is defined as: 1) the detection of 


Statistical Analysis Plan 
 
 
8 
 
any 2 incidents of the same drug-related SAE; or 2) crude ACPR < 60% (equivalent to > 
40% recurrence). 
 
Cohort 2 will test whether pharmacoenhancement of SJ733 with cobicistat is required for 
clinical efficacy. If cohort 2 meets the success criteria, the trial will be complete. If data 
from cohort 2 are inconclusive, an adaptation will be triggered to use the same regimen 
for a larger number of patients in order to improve statistical power and more accurately 
classify a potential failure. If cohort 2 proves safe (no repeated drug-related SAE) but not 
efficacious (crude ACPR < 60%), an adaptation will be triggered to use an intermediate 
exposure of SJ733, obtained by pharmacoenhancement of a reduced dose of SJ733 
(optional cohort 3). Due to the pharmacoenhancing effects of cobicistat, a co-dose of 
SJ733 (300 mg) + cobicistat (150 mg) is expected to yield a higher total plasma exposure 
(median AUC) of SJ733 than a dose of SJ733 (600 mg) alone (Figure 1). The increase in 
plasma exposure is expected to provide increased efficacy. While cohort 3 requires co- 
dosing with a pharmacoenhancer, if successful, this regimen would reduce the quantity of 
SJ733 required by two-fold, lowering cost of goods and potentially improving 
tolerability. 
 
Cohorts 1a and 1b are expected to achieve roughly five-fold higher plasma exposure of 
(+)-SJ733 than Cohorts 2a and 2b. Thus, if Cohorts 1a and 1b prove efficacious but 
repeated drug-related adverse events are observed, the Investigator, DMC, and SRT may 
unanimously agree that no further patients should be recruited to Cohorts 1 but that 
patient recruitment to Cohorts 2 should still be pursued. In this scenario, the Investigator 
will assess the severity/intensity of the adverse reactions and clinical laboratory changes 
using the DMID Toxicity Grading Scale for Determining the Severity of Adverse Events 
provided in Protocol Attachment 3 and Section 8.1.2. This information will be relayed to 
the DMC and SRT, who will make recommendations regarding further conduct of the 
trial, and if considered necessary, may recommend pausing or stopping further 
administration of the investigational product. Cohort progression will only be explored if 
the Investigator, DMC, and SRT unanimously agree it is warranted and appropriate. 
These recommendations will also be communicated to the Ethics Committee and 
Regulatory Authority and any necessary updates will be made to the patient consent 
form. 
 
Each cohort will consist of two treatment arms. Cohort progression for each treatment 
arm will be managed independently of the other treatment arm. For example, if data from 
the P. falciparum cohort (1A) do not meet the success criteria or are inconclusive, but the 
data from the P. vivax cohort (1B) do meet the success criteria, then the P. vivax arm may 
continue to explore reducing levels of SJ733 exposure according to Figure 1 (cohort 2B 
and 3B), while the P. falciparum initial cohort of the study will be expanded or 
terminated. Established antimalarial therapy will be given if a patient meets any of the 
defined treatment failure criteria. Finally, if one treatment arm meets the failure criteria, 
remaining patients who have not received treatment may be reassigned to the other 
treatment arm to improve statistical power. 
 
Study Population 
 
Men and women between the ages of 18 and 70 years with P. falciparum or P. vivax 
malaria monoinfection living in Peru. 2-6 cohorts of adult patients (10 patients per 
cohort) with acute, uncomplicated P. falciparum or P. vivax malaria monoinfection. In 
total, there will be a minimum of 20 and a maximum of 60 patients. 


Statistical Analysis Plan 
 
 
9 
3. Data Elements 
 
Endpoints 
 
Primary endpoints related to efficacy 
For P. vivax: Crude Adequate Clinical and Parasitological Response (ACPR) at Day 14 
defined as the absence of microscopically determined parasitemia (thick smear) on Day 
14, irrespective of axillary temperature, in patients who did not previously meet any of 
the criteria of early treatment failure, late clinical failure, or late parasitological failure. 
 
For P. falciparum: Crude Adequate Clinical and Parasitological Response (ACPR) at 
Day 14 defined as the absence of microscopically determined parasitemia (thick smear) 
on Day 14, irrespective of axillary temperature, in patients who did not previously meet 
any of the criteria of early treatment failure, late clinical failure, or late parasitological 
failure. 
Success criterion: Crude ACPR on Day 14 ≥ 80% (equivalent to ≤ 20% recurrence). 
 
Primary endpoints related to safety and tolerability up to Day 42 
• 
Incidence, severity, drug-relatedness, and seriousness of adverse events 
• 
Proportion of patients with clinically significant abnormal laboratory values 
including changes from baseline (biochemistry and hematology) 
• 
Proportion of patients with clinically significant abnormal vital signs including 
changes from baseline 
• 
Proportion of patients with a decrease in hemoglobin (Hb): > 2 g/dL from 
baseline to an absolute value of < 5 g/dL 
• 
Proportion of patients with an absolute Neutrophil count < 1,000/μL after baseline 
• 
Proportion of patients meeting Hy's law criteria 
• 
Proportion of patients with the following LFT changes: 
▪ Any ALT or AST ≥ 5 x ULN 
▪ Any AST or ALT ≥ 3 x ULN together with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash and/or 
eosinophilia (eosinophil percent or count above the ULN) 
▪ Persistent ALT ≥ 3 x ULN for a period of more than 4 weeks. 
• 
Proportion of patients with clinical signs of possible cutaneous adverse reactions 
such as dermatitis, rash, erythematous rash, macular rash, papular rash, maculo-papular 
rash, pruritic rash, pustular rash, vesicular rash 
• 
Proportion of patients with clinically significant increases in venous 
methemoglobin levels 
• 
Proportion of patients with significant changes in ECG findings, including heart 
rate, ECG intervals (PR, QTcB, QTcF), conduction changes or abnormalities 
 
Success criterion: No repeated drug-related serious adverse events (Attachment 3, 
Section 8.1.2). 
 
Secondary Endpoints 
Secondary endpoints related to malaria signs and symptoms up to Day 42


Statistical Analysis Plan 
 
 
10 
• Proportion of patients with symptoms or physical examination signs related to 
uncomplicated P. vivax or P. falciparum malaria (dizziness, headache, nausea, 
anorexia, vomiting, diarrhea, pruritus, urticaria, skin rash, abdominal pain, joint 
pain, muscle pain, palpitations, sleep disturbance, confusion, hearing 
disturbance, visual disturbance, fatigue) 
• Fever Clearance Time as defined as the time from baseline to the first of two 
consecutive post-dose axillary temperature measurements < 37.5°C obtained 
within an interval of 4 to 24 hours of each other. 
 
Secondary endpoints related to secondary treatment outcomes 
• Crude ACPR at Days 28, 35, and 42 (P. vivax or P. falciparum) 
• Recurrence (P. vivax or P. falciparum) up to Day 42 
Secondary endpoints related to parasite clearance kinetics by microscopy 
• Parasite clearance time (PCT) 
• PRR (parasite reduction rate) and parasitemia half life 
• Times to microscopic clearance of asexual parasites 
▪ Total reduction (PC100) 
▪ 99% reduction (PC99) 
▪ 90% reduction (PC90) 
▪ 50% reduction (PC50) 
• Microscopically determined percentage reduction in asexual parasites from 
baseline at: 
▪ 24 hours after administration of study drug 
▪ 48 hours after administration of study drug 
▪ 72 hours after administration of study drug 
• Proportion of microscopically determined parasitemia in patients at: 
▪ 24 hours after administration of study drug 
▪ 48 hours after administration of study drug 
▪ 72 hours after administration of study drug 
 
Secondary endpoints related to PK parameters up to Day 42 
AUC0-t, AUC0-inf, Cmax, tmax, t½, Cl, F, etc. 
Exploratory Endpoints: 
• PCR-adjusted ACPR at Days 7, 14, 28, 35, and 42 (P. vivax or P. falciparum) 
• PCR determined recurrence (P. vivax or P. falciparum) up to Day 42 
• Correlation between parasite genotypes of interest and parasite clearance 
kinetics/efficacy 
 
Data Sources 
 
Data will be entered into REDCap instruments per the Data Management Plan (DMP). 
Clinical, laboratory, and safety study measures will be entered into the electronic data 
capture system (REDCap) and assessed for quality as outlined in the DMP. 


Statistical Analysis Plan 
 
 
11 
 
Creation of Analysis Datasets and Analytic Data Handling 
 
Data from REDCap will be exported and converted to SAS datasets. Analysis datasets 
will be created, and SAS programs will be developed to further investigate potential data 
issues via simple descriptive statistics and plots. Summary reports will be provided 
periodically during the course of the project to verify accuracy of data entry and provide 
early opportunities for clarification of questions and correction of errors and omissions. 
For analysis datasets, Data Definition Tables (DDTs) are included to document all 
variables (both raw and derived) included in the analysis datasets. This includes the 
variable name, label, type, length, format, coded values and logic for creating derived 
variables. For raw data, a data dictionary is available through REDCap. The data 
dictionary provides a description of all data fields including the field name, label, field 
type, response option coding and branching logic. 
Quality assurance strategies outlined in the DMP will be used to minimize missing data. 
In general, primary analyses will be conducted as observed. In the event imputation is 
needed and appropriate, it will be employed using multiple imputation methods. In the 
presence of imputation, the sample size is not diminished. A description of participant 
disposition will be included to assess incomplete data, visits, withdrawals, deviations, 
and discontinuations. 
4. Statistical Methods 
The overall study design is to demonstrate proof of concept and serves as an exploratory 
study. It is not intended to demonstrate superiority or non-inferiority against a control. 
Rather the goal is to establish preliminary data for planning future studies and to assess 
whether the SJ733 is safe and the observed curative rate equals or exceeds 80%. As such, 
there will be no statistical testing of hypotheses. This exploratory Proof of Concept study 
uses a fixed clinical safety and parasitological responses (primary endpoints) defined as 
the absence of any drug-related SAE or microscopically determined parasitemia 14-days 
after initiation of therapy in ≥ 80% patients who did not violate any of the 
inclusion/exclusion criteria. 


Statistical Analysis Plan 
 
 
12 
General Approach 
 
The overall study design involves two cohorts receiving SJ733 doses (600 mg and 300 
mg) with and without cobicistat (150 mg) as cohorts. Data subsets (eligible, evaluable 
and completer) will be used in the potential comparisons. 
The primary analytic approaches will be descriptive. All data will be summarized 
descriptively for the appropriate analysis sets defined below: Continuous variables by 
descriptive statistics (number of patients [n], mean, standard deviation [SD], minimum, 
median, maximum); categorical data by absolute and relative frequencies (n and %) or 
contingency tables.  
While this is a proof of concept, exploratory study, any potential comparisons between 
dose cohorts will be informative. Potential longitudinal data will be described as 
graphical summaries presented by each group. Unless indicated otherwise, summary 
statistics will be reported for observed data only, by dose cohort.  Missing data will not 
be imputed. If a baseline value is missing, no change from baseline will be calculated.  
Baseline is defined as the last observation prior to the administration of study medication. 
 
SAS v9.4 or higher will be used for all analyses and a significance level of 0.05 will be 
used for all statistical tests. 
 
Primary Analysis (Efficacy) 
 
Primary analyses will be conducted across the two cohorts and by the two cohorts. 
Estimates will be presented with 95% confidence intervals. 
 
The primary efficacy endpoints will be summarized descriptively, across the two 
cohorts and by the two cohorts. A statistical test will not be performed on the Crude 
ACPR on Day 14. Achieving a rate of 80% will be the decision rule for cohort dose 
phase. For future study planning, a one-sample z-test will be used to compare the rate of 
success, as defined by the Crude ACPR on Day 14, to the hypothesized rate of 80%. 
 
Secondary efficacy variables will be summarized descriptively (by cohort; on Days 0, 
14, 42) with proportions, means, and medians. To inform future studies, all estimates 
will be presented with 95% confidence intervals (1.96 ± margin of error). Graphical 
summaries will be used to describe changes in efficacy endpoints over time.  


Statistical Analysis Plan 
 
 
13 
 
Exploratory Analysis 
 
Exploratory model-based analyses will be performed as data allows. These will include 
model-based analyses of PK, PD and PK/PD. 
 
Safety Analysis 
 
Adverse events (AEs) will be summarized in Listing 9: Cumulative Summary of 
Adverse Events. The listing will include the following information: Patient ID, AE 
Description, Start Date, Stop Date, Special Interest, Severity, Relationship to Study 
Drug, Action Taken, Outcome of AE, Expected AE, and if the AE was a Serious 
Adverse Event (SAE). 
 
Laboratory values that fall outside a clinically accepted reference range must be 
evaluated and commented on by the Investigator and graded according to the DMID 
Toxicity Scale for Determining Severity of Adverse Events (Protocol Attachment 3, 
Section 8.1.2). 
 
All related AEs, AEs with outcome death, AEs leading to permanent discontinuation 
of treatment, SAEs and related SAEs will be summarized in Listing 10: Cumulative 
Summary of Serious Adverse Events. The listing will include the following 
information: Patient ID, Age, Sex, Dose, SAE Description, Start Date, Stop Date, SAE 
Category, and Relationship to Study Drug.  
 
Treatment related AEs are those rated by the Investigator as “definite”, “probable”, 
“possible”. In case relationship is unknown or missing the worst case will be assumed 
and the AE will be considered to be drug related 


 
14 
 
Planned Interim Analyses 
 
Interim analyses will be made to review parasite reduction, adverse events, and clinical 
laboratory data. Following review, a decision on cohort progression will be made. 
However, as this is an exploratory study no formal analyses with adjustments for type I 
error are planned. 
 
The following rules will be used as general guidelines to aid the decision of cohort 
progression: 
• Curing ≥8/10 patients without any repeated drug-related SAEs then explore 
lower dose; 
• Curing 6/10 or 7/10 patients without any repeated drug-related SAEs would be 
inconclusive and as a result we would expand the treatment arm; 
• Curing ≤5/10 is failure which would stop the trial in Cohort 1. 
 
Strategies to Minimize Bias 
 
Given the nature of the study, issues related to randomization/blinding/masking do not 
apply. 
 
Sample Size Justification 
 
The sample size for this exploratory Proof of Concept study was based on primary 
efficacy hypothesis. A one-sample z-test will have at least 85% power to detect the 
difference between the hypothesized curative rate (80%) with an alternative curative rate 
of 98%, assuming a one-sided significance level of 0.05, when the sample size is 20. All 
primary analyses will pool parasite arms within cohort dose. As such, a sample size of 
10 patients per dose cohort arm was considered adequate to gain efficacy and safety data 
in patients with P. falciparum and P. vivax or to permit evaluation of MIC and MEC as 
per similar studies conducted. If patients drop out for reasons unconnected to efficacy, 
attempts will be made to replace them to try to ensure the maximum number in each 
cohort. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
15 
 
5. Planned Tables, Listings, and Figures. 
 
 
Number 
Tables* 
*Tables will be provided overall and by cohort 
Table 1 
Patient Status  
Table 2 
Patient Demographics and Baseline Characteristics 
Table 3 
Malaria Sign and Symptoms 
Table 4 
Clinical Laboratory Summary  
Table 5 
Vital Signs 
Table 6 
12-LEAD ECG Summary  
Table 7 
Primary Endpoint  
Figures  
Figure 1 
Patient Status  
Figure 2a 
Efficacy: Asexual Parasite Count Over Time Up to Day 42 – Microscopist Report 1 
Figure 2b 
Efficacy: Asexual Parasite Count Over Time Up to Day 42 – Microscopist Report 2 
Figure 3- 
qPCR Values Over Time Up to Day 42 
Figure 4a 
Crude ACPR – Microscopist Report 1 
Figure 4b 
Crude ACPR – Microscopist Report 2 
Figure 5 
eDISH Plot  
Figure 5a 
Liver Testing by Patient  
Figure 6 
Total Bilirubin Lab Result (mg/dL) Over Time  
Figure 7 
Albumin Lab Result (g/dL) Over Time 
Figure 8  
ALT/SGPT Lab Result (U/L) Over Time 
Figure 9 
AST/SGOT Lab Result (U/L) Over Time 
Figure 10 
LDH Lab Result (U/L) Over Time 
Figure 11 
Alkaline Phosphate Lab Result (U/L) Over Time 
Figure 12 
Creatine Kinase Lab Result (mg/dL) Over Time 
Figure 13a 
Creatine Kinase Lab Result (mg/dL) Over Time for Males 
Figure 13b 
Creatine Kinase Lab Result (mg/dL) Over Time for Females 
Figure 14 
Urea Lab Result (mg/dL) Over Time 
Figure 15 
Sodium Lab Result (mmol/L) Over Time 
Figure 16 
Potassium Lab Result (mmol/L) Over Time 
Figure 17  
Glucose Lab Result (mg/dL) Over Time 
Figure 18 
Temperature (ºC) Over Time – Overall  
Figure 18a 
Temperature (ºC) Over Time – Day 1  
Figure 18b 
Temperature (ºC) Over Time – Day 1-5 
Figure 19 
Leukocyte Total (/mm3) Over Time  
Figure 20 
Erythrocyte Count (/uL) Over Time 
Figure 21a 
Hemoglobin (g/dL) Over Time for Females 
Figure 21b 
Hemoglobin (g/dL) Over Time for Females 
Figure 22a 
Hematocrit (%) Over Time for Males  
Figure 22 b Hematocrit (%) Over Time for Females 
Figure 23 
Methemoglobin (%) Over Time 
Figure 24 
Platelet Count (/mm3) Over Time  


 
16 
 
Figure 25 
Haptoglobin (mg/dL) Over Time  
Figure 26 
Neutrophil (/mm3) Over Time 
Figure 27 
Absolute Lymphocyte (/mm3) Over Time 
Figure 28 
Absolute Eosinophils (/mm3) Over Time 
Figure 29 
Absolute Basophils (/mm3) Over Time 
Figure 30 
Absolute Monocytes (/mm3) Over Time 
Figure 31 
Absolute Reticulocytes (%) Over Time 
Listings 
Listing 1 
Baseline Parasite Count 
Listing 2 
Efficacy: Asexual parasite count over time up to Day 42 
Listing 3 
qPCR Value over time up to Day 42 
Listing 4 
Fever Clearance Time  
Listing 5 
Medication History 
Listing 6 
Concomitant History  
Listing 7 
Malaria Signs and Symptoms  
Listing 8 
Definitive Antimalarial Treatment  
Listing 9 
Cumulative Summary of Adverse Events 
Listing 10 
Cumulative Summary of Serious Adverse Events 
 
6. Planned Start and End of Analysis 
 
Start of analysis: 05/2021 
End of analysis:  12/2022