ANZCTR - Registration

Registration number

ACTRN12620000766910

Ethics application status

Approved

Date submitted

12/06/2020

Date registered

27/07/2020

Date last updated

16/09/2021

Date data sharing statement initially provided

27/07/2020

Type of registration

Prospectively registered

Titles & IDs

Public title

An Open-label Phase 1b Cross-over Pharmacokinetic Relative Bioavailability Study Comparing 2 Formulations of STG-001 in Healthy Subjects

Scientific title

An Open-label Phase 1b Cross-over Pharmacokinetic Relative Bioavailability Study Comparing 2 Formulations of STG-001 in Healthy Subjects

Secondary ID [1]

STG-001-1b

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Stargardt's Disease

Condition category

Condition code

Eye

Diseases / disorders of the eye

Human Genetics and Inherited Disorders

Other human genetics and inherited disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Intervention: STG-001
Administration: Oral capsule
Part 1: Single dose study
10 participants will receive a single dose of active 30mg unmilled STG-001 capsules. Participants will be dosed in clinic by study nurses to ensure adherence to the intervention.

Part 2: Single dose study
Subjects in Part 1 will return after washout of >= 3 weeks; The same 10 participants will receive active 30mg of milled capsules of STG-001
Participants will be dosed in clinic by study nurses to ensure adherence to the intervention.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Open label study, no control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Part 1: The primary endpoint of the study is safety assessed by incidence and/or clinically significant changes of a combination of ocular and non-ocular adverse events of single oral dose of Formulation 1 of STG-001 in healthy subjects.
Systemic adverse reactions will be assessed by physical exam, vital signs, ECG and blood testing (CBC,chemistry, and urinalysis). Ocular adverse reactions, including delayed dark adaptation, will be assessed by ocular exam, visual acuity and color vision testing, intraocular pressure testing, retina exam and a night vision questionnaire. Additional diagnostic testing to monitor ocular adverse events will include , fundus autofluorescence and dark adaptometry.

Timepoint [1]

Adverse Events: Day -1, Day 1, Day 2, Day 3, Day 4 and Day 8
Clinical Laboratory Tests: Screening, Day -1, Day 2 and Day 8
Vital Signs: Screening, Day -1, Day 1, Day 2, Day 3 and Day 8
ECG: Screening, Day 1, Day 2 and Day 8
Physical Examination: Screening, Day -1, Day 3 and Day 8
Dark Adaptometry (DA): Screening, Day 3 and Day 8
BCVA - ETDRS: Screening, Day 3 and Day 8
IOP: Screening, Day 3 and Day 8
Subjective Refraction: Screening, Day 3 and Day 8
Biomicroscopy: Screening, Day 3 and Day 8
Fundus Exam: Screening, Day 3 and Day 8
Night Vision Questionnaire: Screening, Day 3 and Day 8
Telemetry Monitoring: Day 1 and Day 2

Primary outcome [2]

Part 2: The primary endpoint of the study is safety assessed by incidence and/or clinically significant changes of a combination of ocular and non-ocular adverse events of a single oral dose of Formulation 2 of STG-001 in healthy subjects. Systemic adverse reactions will be assessed by physical exam, vital signs, ECG and blood testing (CBC,chemistry, and urinalysis). Ocular adverse reactions, including delayed dark adaptation, will be assessed by ocular exam, visual acuity and color vision testing, intraocular pressure testing, retina exam and a night vision questionnaire. Additional diagnostic testing to monitor ocular adverse events will include , fundus autofluorescence and dark adaptometry.

Timepoint [2]

Adverse Events: Day 21, Day 22, Day 23, Day 24, Day 25 and Day 29
Clinical Laboratory Tests: Day 21, Day 23 and Day 29
Vital Signs: Day 21, Day 22, Day 23, Day 24 and Day 29
ECG: Day 21, Day 22, Day 23 and Day 29
Physical Examination: Day 21, Day 24 and Day 29
Dark Adaptometry (DA): A single Dark Adaptometry will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
BCVA - ETDRS: A single BCVA-EDTRS will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
IOP: A single IOP will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
Subjective Refraction: A single subjective refraction will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
Biomicroscopy: A single Biomicroscopy will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
Fundus Exam: A single Fundus exam will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
Night Vision Questionnaire: Day 21, Day 24 and Day 29
Telemetry Monitoring: Day 22 and Day 23

Secondary outcome [1]

Parts 1 and 2: Percentage of subjects who experience at least 1 TEAE (Treatment emergent adverse event).

Timepoint [1]

Part 1
Adverse Events: Day -1, Day 1, Day 2, Day 3, Day 4 and Day 8
Clinical Laboratory Tests: Screening, Day -1, Day 2 and Day 8
Vital Signs: Screening, Day -1, Day 1, Day 2, Day 3 and Day 8
ECG: Screening, Day 1, Day 2 and Day 8
Physical Examination: Screening, Day -1, Day 3 and Day 8
Dark Adaptometry (DA): Screening, Day 3 and Day 8
BCVA - ETDRS: Screening, Day 3 and Day 8
IOP: Screening, Day 3 and Day 8
Subjective Refraction: Screening, Day 3 and Day 8
Biomicroscopy: Screening, Day 3 and Day 8
Fundus Exam: Screening, Day 3 and Day 8
Night Vision Questionnaire: Screening, Day 3 and Day 8
Telemetry Monitoring: Day 1 and Day 2

Part 2
Adverse Events: Day 21, Day 22, Day 23, Day 24, Day 25 and Day 29
Clinical Laboratory Tests: Day 21, Day 23 and Day 29
Vital Signs: Day 21, Day 22, Day 23, Day 24 and Day 29
ECG: Day 21, Day 22, Day 23 and Day 29
Physical Examination: Day 21, Day 24 and Day 29
Dark Adaptometry (DA): A single Dark Adaptometry will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
BCVA - ETDRS: A single BCVA-EDTRS will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
IOP: A single IOP will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
Subjective Refraction: A single subjective refraction will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
Biomicroscopy: A single Biomicroscopy will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
Fundus Exam: A single Fundus exam will be conducted between Days 14-20, subsequent tests will be performed on Day 24 and Day 29,
Night Vision Questionnaire: Day 21, Day 24 and Day 29
Telemetry Monitoring: Day 22 and Day 23

Secondary outcome [2]

Parts 1 and 2: Percentage of subjects who discontinue due to an AE.
Occurance of any AEs will be checked at all visits during the study duration until DAy 29. The research team will review timing of discontinuation in relation to AE.

Timepoint [2]

AE will be monitored on an ongoing basis and at every visit until Day 29

Secondary outcome [3]

Parts 1 and 2: Percentage of subjects who meet the markedly abnormal criteria for safety laboratory tests (CBC, Biochemistry and Urinalysis) at least once post-dose. This is assessed based on clinical observation and Investigator's assessment.

Timepoint [3]

Part 1 - Clinical Laboratory Tests: Screening, Day -1, Day 2 and Day 8
Part 2 - Clinical Laboratory Tests: Day 21, Day 23 and Day 29

Secondary outcome [4]

Parts 1 and 2: Percentage of subjects who meet the markedly abnormal criteria for vital sign measurements at least once post-dose. This is assessed based on clinical observation and Investigator's assessment.

Timepoint [4]

Part 1 - Vital Signs: Screening, Day -1, Day 1, Day 2, Day 3 and Day 8
Part 2 - Vital Signs: Day 21, Day 22, Day 23, Day 24 and Day 29

Secondary outcome [5]

Parts 1 and 2: Percentage of subjects who meet the markedly abnormal criteria (clinically significant as by the clinical investigator) for safety 12-lead ECG parameters at least once post-dose.

Timepoint [5]

Part 1 - ECG: Screening, Day 1, Day 2 and Day 8
Part 2 - ECG: Day 21, Day 22, Day 23 and Day 29

Secondary outcome [6]

Parts 1 and 2: Maximum observed plasma concentration (Cmax).

Timepoint [6]

Part 1 - PK sample collection timepoints: Day 1 (Pre-dose and 1, 2, 4, 8 and 12 hours post-dose), Day 2 (24 hours post-dose), Day 3 (48 hours post-dose), Day 4 (72 hours post-dose) and Day 8.
Part 2 - PK sample collection timepoints: Day 22 (Pre-dose and 1, 2, 4, 8 and 12 hours post-dose), Day 23 (24 hours post-dose), Day 24 (48 hours post-dose), Day 25 (72 hours post-dose) and Day 29.

Secondary outcome [7]

Parts 1 and 2: Time to reach Cmax (tmax).
Blood samples will be collected for PK assessments

Timepoint [7]

Part 1 - PK sample collection timepoints: Day 1 (Pre-dose and 1, 2, 4, 8 and 12 hours post-dose), Day 2 (24 hours post-dose), Day 3 (48 hours post-dose), Day 4 (72 hours post-dose) and Day 8.
Part 2 - PK sample collection timepoints: Day 22 (Pre-dose and 1, 2, 4, 8 and 12 hours post-dose), Day 23 (24 hours post-dose), Day 24 (48 hours post-dose), Day 25 (72 hours post-dose) and Day 29.

Secondary outcome [8]

Parts 1 and 2: Area under the plasma concentration-time curve from time 0 to infinity (AUC infinity) and or AUC0 to t.

Timepoint [8]

Part 1 - PK sample collection timepoints: Day 1 (Pre-dose and 1, 2, 4, 8 and 12 hours post-dose), Day 2 (24 hours post-dose), Day 3 (48 hours post-dose), Day 4 (72 hours post-dose) and Day 8.
Part 2 - PK sample collection timepoints: Day 22 (Pre-dose and 1, 2, 4, 8 and 12 hours post-dose), Day 23 (24 hours post-dose), Day 24 (48 hours post-dose), Day 25 (72 hours post-dose) and Day 29.

Secondary outcome [9]

Parts 1 and 2: Terminal elimination half-life (t1/2).
Blood samples will be collected for PK assessments

Timepoint [9]

Part 1 - PK sample collection timepoints: Day 1 (Pre-dose and 1, 2, 4, 8 and 12 hours post-dose), Day 2 (24 hours post-dose), Day 3 (48 hours post-dose), Day 4 (72 hours post-dose) and Day 8.
Part 2 - PK sample collection timepoints: Day 22 (Pre-dose and 1, 2, 4, 8 and 12 hours post-dose), Day 23 (24 hours post-dose), Day 24 (48 hours post-dose), Day 25 (72 hours post-dose) and Day 29.

Secondary outcome [10]

PD of STG-001 (plasma RBP4 levels) parameters: % reduction from baseline, % with >60% reduction from baseline. Blood samples will be collected for PD assessments

Timepoint [10]

Part 1 - PD sample collection timepoints: Day 1 (Pre-dose), Day 2 and Day 8.
Part 2 - PD sample collection timepoints: Day 1 (Pre-dose), Day 22, Day 23 and Day 29.

Secondary outcome [11]

PD of STG-001 (plasma Vitamin A (retinol levels)) parameters: % reduction from baseline. Blood samples will be collected for Vitamin A (retinol level) assessment

Timepoint [11]

Part 1 - PD sample collection timepoints: Day 1 (Pre-dose), Day 2 and Day 8.
Part 2 - PD sample collection timepoints: Day 1 (Pre-dose), Day 22, Day 23 and Day 29.

Eligibility

Key inclusion criteria

The subject must understand the study procedures and agree to participate by providing written informed consent. The subject must be willing and able to comply with all study procedures and restrictions.
To be eligible for participation in this study, the subject must:
1. Understand the study procedures and agree to participate by signing an approved informed consent form for the study.
2. Healthy male and female subjects.
3. Subjects aged 18 to 55 years, inclusive, with BMI of 18 to 32 kg/m2, inclusive, and body weight greater than or equal to 50 kg.
4. Male subjects must abstain from heterosexual activities or agree to use a highly effective double barrier method of contraception from admission to the clinical unit through 90 days after the last dose of study drug (except if female partner is documented to be post-menopausal) and will not donate sperm during this period. Heterosexual women of child-bearing potential (WOCBP) who are sexually active must not be pregnant upon entering the study that is confirmed by testing (i.e., serum pregnancy test with sensitivity of greater than or equal to 25 mIU/mL at screening, and urine pregnancy test with sensitivity greater than or equal to 25 mIU/mL on Day 1 prior to dosing), be willing to use a highly effective double-barrier contraception from screening through 60 days after the last dose of study drug, and will not donate eggs during this period. Highly effective double barrier contraception is defined as a condom AND one of the following highly effective methods;
o Birth control pills (The Pill)
o Birth Control Patch (e.g. Ortho Evra)
o NuvaRing®
o Depot or injectable birth control
o IUD
o Contraceptive implant (e.g. Implanon)
o Documented evidence of surgical sterilization at least 6 months prior to screening visit, i.e., tubal ligation or hysterectomy for women or vasectomy for men.
5. Pre-study ocular exam with no clinically significant abnormalities, including no significant macular abnormalities, DA testing within normal limits and BCVA greater than or equal to 20/50 visual acuity (or equivalent)
6. Willing and able to comply with the protocol, including attending assessment visits.
7. Be judged to be in good health by the Investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, ECG, and vital sign measurements performed at the screening visit and before administration of the initial dose of study drug.

Minimum age

18 Years

Maximum age

55 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Any subject who meets any of the following criteria will not qualify for entry into the study:
1. The subject has a known hypersensitivity or contraindication to any component of STG 001.
2. The subject has any history of an anaphylaxis event.
3. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to Check-in (Day -1). Herbal supplements and HRT must be discontinued 28 days prior to Check-in (Day -1). As an exception, paracetamol may be used at doses of less than or equal tov1 g/day. Limited use of nonprescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the Principal Investigator and the Sponsor.
4. The subject has a history of vitamin A deficiency or clinical signs during slit lamp examination (conjunctival or corneal xerosis; Bitot’s spots; corneal ulcers of scarring not due to trauma or other secondary causes).
5. Has taken non-approved items (supplement containing vitamin A or beta-carotene, liver-based products (foods, such as liverwurst, are not an exclusion), or prescription oral retinoid medications) within 30 days prior to admission at the clinical site.
6. Use of medications that may interact with Vitamin A metabolism within 60 days of screening (e.g. Accutane [isotretinoin], doxycycline).
7. Participation in an interventional study of a Vitamin A derivative less than or equal to 3 months prior to screening
8. Presence of significant cardiovascular or cerebrovascular disease, including stroke.
9. Has a clinically significant abnormal electrocardiogram (ECG), or has a corrected QT interval (QTc) that is 450 ms or greater
10. Resting heart rate outside specified limits (less than 40/minute, greater than 100/min upon repeated measurement).
11. History of diabetes, hepatitis, pancreatitis, cirrhosis, liver failure, uncontrolled thyroid disease or hypervitaminosis A.
12. Any surgical procedure within three month of trial entry or anticipated during the trial. If such surgical procedure was within 3 months of trial entry and there was a full recovery with no expected impact on study procedures, data or safety, such a subject would be eligible at the discretion of the PI.
13. Women who are pregnant or nursing.
14. Abnormal blood pressure outside specified limits (90 mm Hg > Systolic > 140 mm Hg and/or 40 mm Hg > Diastolic > 90 mm Hg) upon repeated measurement.
15. Clinically significant abnormal lab results at screening, including liver function test (aspartate transaminase, alanine transaminase, bilirubin and alkaline phosphatase) greater than 1.5 x the ULN
16. Actively participating in an experimental therapy study or have received experimental therapy within 60 days or 5 half-lives, whichever is longer, of screening.
17. Any history of significant eye disorders (including retinal disorders) or visual disturbances.
18. In the PI’s opinion, any acute or chronic medical condition, psychiatric condition, physical examination finding or laboratory abnormality that may increase the risk associated with study participation or administration of study treatment or interfere with the interpretation of study results. Minor medical conditions that are not currently being treated with medication and that are not expected to interfere with study procedures, data or participant safety may be considered for inclusion at the discretion of the PI.
19. Participants could be at increased risk of harm or put other people at increased risk of harm (e.g. if they are taxi or Uber drivers), if they were to experience visual impairment like impaired night time vision. Participants must agree to comply with advice of study investigators or study ophthalmologist around modifying activity and taking precautions if visual impairment occurs until such time as the visual impairment resolves, or the participant will be excluded from the study.

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

29/07/2020

Actual

27/07/2020

Date of last participant enrolment

Anticipated

29/07/2020

Actual

27/07/2020

Date of last data collection

Anticipated

31/08/2020

Actual

24/08/2020

Sample size

Target

10

Accrual to date

Final

10

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Nucleus Network - Melbourne

Recruitment postcode(s) [1]

3004 - Melbourne

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Stargazer Pharmaceuticals, Inc.

Country [1]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Stargazer Pharmaceuticals, Inc.

Country

United States of America

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee

Ethics committee address [1]

55 Commercial Rd, Melbourne, VIC 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

04/06/2020

Approval date [1]

29/06/2020

Ethics approval number [1]

Summary

Brief summary

Stargazer Pharmaceuticals. is developing STG-001 a potential oral therapy for patients with Stargardt's disease.
This study will be conducted in 10 healthy volunteers who meet all of the inclusion criteria and none of the exclusion criteria. The study is to assess the safety and tolerability of STG-001 in normal healthy volunteers. This includes vital signs, safety labs, ECGs, and ocular and non-ocular examinations.
The drug will be given in single dose of unmilled STG001 capsules in part 1 and after a washout period a single dose of milled capsules in part 2.
The study will also evaluate the PK and PD of the drug after dose administration.
Participants will be entered into standard study cohorts

Trial website

Public notes

Contacts

Principal investigator

Name

Dr Ben Snyder

Address

Nucleus Network Pty Ltd
5th Floor, Burnet Tower, AMREP Precinct
Commercial Road, Melbourne
VIC, 3004

Country

Australia

Phone

+61 3 9076 8960

Email

b.snyder@nucleusnetwork.com.au

Contact person for public queries

Name

Jasmine Panthaki

Address

Nucleus Network Pty Ltd
5th Floor, Burnet Tower, AMREP Precinct
Commercial Road, Melbourne
VIC, 3004

Country

Australia

Phone

+61 3 9089 8247

Email

J.Panthaki@nucleusnetwork.com.au

Contact person for scientific queries

Name

Gary Sternberg

Address

Stargazer Pharmaceuticals Inc
200 Clarendon Street, 45 floor, Mailbox 30
Boston, MA 02116

Country

United States of America

Phone

+1 510 913 8357

Email

sternberg@stargazerpharma.com

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