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Trial registered on ANZCTR


Registration number
ACTRN12622000405718
Ethics application status
Approved
Date submitted
27/01/2022
Date registered
9/03/2022
Date last updated
4/08/2023
Date data sharing statement initially provided
9/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of ONC201 on participants with renal impairment
Scientific title
A Phase 1 study to evaluate the effect of renal impairment on the pharmacokinetics of ONC201
Secondary ID [1] 306283 0
ONC201-104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 325040 0
Solid Tumours 325041 0
Renal Impairment 325042 0
Condition category
Condition code
Cancer 322473 322473 0 0
Any cancer
Renal and Urogenital 322709 322709 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ONC201 (investigational drug) will be dosed, as a single dose, 375 mg capsule orally, at one time only to the following groups:
Arm 1 - 8 x Participants with severe renal impairment

Adherence to intervention will be via mouth check of swallowed capsule.
Intervention code [1] 322711 0
Treatment: Drugs
Comparator / control treatment
Arm 2 - 8 x Healthy Volunteers matched with each participant in Arm 1 by age (± 10 years), BMI (± 20%), and sex (match).

The renal impairment group and matched volunteers will each receive oral ONC201 capsules 375mg, once only.
Adherence to intervention will be via mouth check of swallowed capsule.
Control group
Active

Outcomes
Primary outcome [1] 330255 0
To determine the effect of severe renal impairment on ONC201 plasma PK following a single 375 mg dose of ONC201 administered orally
Timepoint [1] 330255 0
Plasma ONC201 PK parameters: AUCinf, Cmax, Tmax,
AUClast, %AUCextrap, t1/2, CL/F, Vz/F measured at the following timepoints: Predose (within 15 minutes prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4,
6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 168 hours post dose.
Secondary outcome [1] 405478 0
To evaluate the safety and tolerability of a 375 mg ONC201 dose administered orally to participants with severe renal impairment compared to healthy matched participants
Timepoint [1] 405478 0
Clinical and laboratory safety parameters including:
-adverse events (AEs) - continuously Screening through to Day 14
non absolute and changes over time of hematology and clinical chemistry - at Screen. Day -1, Day 3, Day 8 and Day 14 post dose
Vital signs (pulse, Blood pressure,temperature and respiratory rate) - at Screen, Day -1, Day 2, Day 3, Day 4, Day 8 and Day 14 post dose
Neurological assessments (NANO assessment) at Screen, Day -1, Day 2, Day 3, Day 4, Day 8 and Day 14 post dose
ECG intervals at Screen, Day -1, Day 2, Day 3, Day 8 and Day 14 post dose
Secondary outcome [2] 405479 0
To characterize ONC201 on urine PK following a single 375 mg dose of ONC201 administered orally
Timepoint [2] 405479 0
Urinary PK measures - Ae, Ae(%), CLr at Day 1 - 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post dose
Secondary outcome [3] 405480 0
To characterize metabolite ONC207 plasma and urine PK following a single 375 mg dose of ONC201 to healthy and renal impaired participants, as available
Timepoint [3] 405480 0
PK parameters : Plasma ONC207 Cmax, Tmax, AUClast,
AUCinf, %AUCextrap, t1/2 at Day 1, Day2, Day 3, Day 4 Day 8 and Day 14 post dose
Urine ONC207 PK: Ae, Ae(%) at Day 1.- 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post dose

Eligibility
Key inclusion criteria
Healthy Volunteers:
1. Male or female between 18 to 75 years of age.
2. Females: non-childbearing potential
3. Males: surgically sterilized OR agree to use an acceptable method(s) of contraception
during heterosexual intercourse.
4. Males to refrain from sperm donation during the study and for at least 90 days
after study drug administration.
5. Weight at least 50 kg and a body mass index from 18 to 40 kg/m2.
6. Normal renal function as defined by eGFR greater than or equal to 90 mL/min
7. Similar demography to a subject enrolled with severe renal impairment for sex, age
(± 10 years), and BMI (± 20%).
8. Blood pressure between 70 and 150 mmHg systolic (inclusive) and not higher than
90 mmHg diastolic.
Renal Impairment:
1. eGFR less than 30 mL/min
2. No clinically significant change in disease status within the last 30 days before screening,
3. Conditions consistent with renal impairment and associated symptoms a
4.. If diabetic, disease must be under control
5.. Blood pressure between 70 and 160 mmHg systolic (inclusive) and not higher than
100 mmHg diastolic.
6. Concomitant medications to treat underlying disease states or medical conditions
associated with renal impairment are allowed. Stable doses of medications for at least
2 weeks prior to dosing and throughout the study are required
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Healthy volunteers:
1. If male, have a female partner who is pregnant or planning to become pregnant during the study or within 90 days after study drug administration.
2. If female, is lactating.
3. Have a positive pregnancy test at screening or Day -1.
4. Have received any investigational drug, agent, or device within 30 days prior to Day 1, or
current participation in another investigational study.
5. Have a positive serological test result at the screening evaluation consistent with possible infection with HBV, HCV, or HIV.
6. Have a positive test for drugs of abuse and/or alcohol at either the screening or Day -1.
7. Current history of heavy tobacco/nicotine use.
8. Have any serious or active medical or psychiatric illness,
9. Have a history of a gastrointestinal condition or disorder that could interfere with the
absorption of the study drug
10. Have a history of hematological disorders, including disorders such as a bleeding
disorder or a risk of gastrointestinal bleeding.
11. Have a history of chronic liver disease or hepatic impairment,
12. Total bilirubin greater than the upper limit of the normal reference range at screening or
on Day -1.
13. Have symptoms of acute infection within 2 weeks prior to Day 1.
14. Have a clinically significant history of difficulty with blood donation
16. Have donated a unit of blood or had clinically significant blood loss within 30 days prior
to Day 1 or donated plasma within 7 days prior to Day 1.
17. Have a history of clinically relevant drug or alcohol abuse or dependence
18. Have consumed grapefruit, pomegranate, or fruit juice within 3 days prior to Day 1,
19.. History of clinically significant renal illness or abnormalities.
20. Have received any medication or herbal product known to induce or inhibit hepatic metabolizing enzymes within 30 days or 5 half-lives of the compound
21. Have received any prescription medication, vaccines (including COVID vaccination), or
any nonprescription medication (including vitamins and herbal products) within 14 days
prior to Day 1,
22. Have a history or symptoms of cardiovascular disease,

Subjects with Renal Impairment
1. History of renal transplant
2. Acute or exacerbating renal disease OR fluctuating or deteriorating renal function as
indicated by widely varying or worsening signs of renal impairment within 4 weeks of
screening.
3. Significant bleeding disorders that could preclude multiple venipuncture procedures
4. Paracetamol > 1 g/day within 2 weeks of dosing.
5. Clinically significant vital sign abnormalities at screening or Day -1.
6.. Clinically significant physical, laboratory, or ECG findings apart from those related to impaired renal function or underlying disease .
Subjects with Normal Renal Function
7. History of clinically significant renal illness or abnormalities.
8. Have received any medication or herbal product (e.g., St. John’s wort) known to induce
or inhibit hepatic metabolizing enzymes and/or transporters within 30 days or 5 half-lives
of the compound, whichever is longer, prior to Day 1.
9. Have received any prescription medication, vaccines (including COVID vaccination), or
any nonprescription medication (including vitamins and herbal products) within 14 days
or 5 half-lives of the compound, whichever is longer, prior to Day 1, unless approval is
granted by both the investigator and the sponsor.
10. Have a history or symptoms of cardiovascular disease, including but not limited to
coronary artery disease, hypertension, congestive heart disease, and clinically significant
cardiac arrhythmia or conduction disorder, or an abnormal ECG thought to be potentially
clinically significant per the investigator at screening or Day -1, or QTcF > 450 ms for
males and > 470 ms for females.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
There are no formal pre-specified statistical hypotheses. Approximately 8 participants with severe renal impairment and 8 healthy participants that are matched 1:1 (based on age [± 10 years], BMI [± 20%] and sex [match]) to the renal impairment cohort will be enrolled to achieve a minimum of 6 evaluable participants in each cohort. These sample sizes were determined based on feasibility in order to provide adequate assessment of PK and safety.
PK parameters following single-dose administration will be determined using standard
noncompartmental methods and actual sampling times utilizing a PK data analysis program (e.g., Phoenix WinNonlin or equivalent).
Safety will be assessed through AEs, measurement of vital signs, ECGs, neurological
assessments, and clinical laboratory test results. All AEs reported and any concomitant
medication intake will also be documented.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2022
Actual
23/05/2022
Date of last participant enrolment
Anticipated
30/07/2022
Actual
20/04/2023
Date of last data collection
Anticipated
15/08/2022
Actual
12/05/2023
Sample size
Target
16
Accrual to date
Final
16
Recruitment outside Australia
Country [1] 24528 0
New Zealand
State/province [1] 24528 0
Christchurch

Funding & Sponsors
Funding source category [1] 310630 0
Commercial sector/Industry
Name [1] 310630 0
Chimerix, Inc.
Country [1] 310630 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Chimerix, Inc.
Address
2505 Meridian Parkway,
Suite 100, Durham, NC
USA 27713
Country
United States of America
Secondary sponsor category [1] 311843 0
None
Name [1] 311843 0
Address [1] 311843 0
Country [1] 311843 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310233 0
NZ Health & Disability Ethics Committee
Ethics committee address [1] 310233 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
New Zealand
Ethics committee country [1] 310233 0
New Zealand
Date submitted for ethics approval [1] 310233 0
10/02/2022
Approval date [1] 310233 0
29/03/2022
Ethics approval number [1] 310233 0

Summary
Brief summary
ONC201 is an investigational drug being developed to treat high grade glioma (a type of brain cancer). “Investigational” means that the FDA (the U.S. Food and Drug Administration) has not approved ONC201 as a treatment for this condition. ONC201 is a newly discovered compound that may stop cancer cells from growing. This drug has been shown in laboratory experiments to use a new way to kill brain tumor cells but not normal cells.
The study is designed to investigate the pharmacokinetics (PK), safety, and tolerability of a
single dose of ONC201 in subjects with severe renal impairment compared with matched control subjects with normal renal function. The study will fully characterize the PK of ONC201 and its metabolite ONC207 in plasma and urine.
This is an open-label, single-period, single-dose study conducted with approximately 8 participants (Cohort 1) with severe renal impairment and 8 healthy matched participants (Cohort 2) with normal renal function. Cohort 2 participants will be matched with Cohort 1 participants based on age (± 10 years), body mass index (BMI) (± 20%), and sex (match).
All participants will receive a single dose of 375 mg ONC201 (3 x 125 mg capsules) with 240 mL of room temperature water following a 10-hour fast.
Screening evaluations will be performed no more than 28 days prior to the dosing (Day 1) to identify participants eligible to participate in the study. Eligible participants will be admitted to the clinic facility on Day -1, the day prior to dosing, Participants will remain in the clinic until discharge on the morning of Day 3 following completion of all scheduled study procedures and assessments.
Participants will return for outpatient visits on Days 4 and 8.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116942 0
Dr Nicholas Cross
Address 116942 0
New Zealand Clinical Research- Christchurch
264 Antigua Street
Christchurch 8140
Country 116942 0
New Zealand
Phone 116942 0
+64 3 3729477
Fax 116942 0
Email 116942 0
[email protected]
Contact person for public queries
Name 116943 0
Joanne Sanders
Address 116943 0
New Zealand Clinical Research- Christchurch
264 Antigua Street
Christchurch 8140
Country 116943 0
New Zealand
Phone 116943 0
+64 3 3729477
Fax 116943 0
Email 116943 0
[email protected]
Contact person for scientific queries
Name 116944 0
Nicholas Cross
Address 116944 0
New Zealand Clinical Research - Christchurch
264 Antigua Street
Christchurch 8140
Country 116944 0
New Zealand
Phone 116944 0
+64 3 3729477
Fax 116944 0
Email 116944 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.