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Trial registered on ANZCTR


Registration number
ACTRN12624000898550p
Ethics application status
Submitted, not yet approved
Date submitted
3/07/2024
Date registered
24/07/2024
Date last updated
24/07/2024
Date data sharing statement initially provided
24/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Investigate the Safety of SEP-786 101 Capsules Compared With Placebo Capsules in Healthy Volunteer Participants Aged 24 Through 55 Years
Scientific title
A Phase 1, Double Blind, Randomized, Placebo Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral Doses of SEP-786 in Healthy Adult Participants (SEP-786 Phase 1 SAD and MAD)
Secondary ID [1] 312387 0
SEP-786-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypoparathyroidism 334190 0
Condition category
Condition code
Metabolic and Endocrine 330849 330849 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be conducted in to 3 parts. Part 1 will evaluate single ascending doses (SAD) of SEP-786 administered orally as capsule on Day 1 in healthy participants. It will consist of a maximum of 8 cohorts and each cohort will consist of up to 10 healthy participants. Participants will be randomized to SEP-786 or placebo (up to 80 participants total) in 1 of the 8 treatment cohorts. The dose range for SEP-786 will be between 5 mg and 200 mg.

Part 2 will evaluate once-daily multiple ascending doses (MAD) of SEP-786 from Day 1 through 5. It will consist of a maximum of 4 cohorts and each cohort will consist of up to 10 healthy participants. Participants will be randomized to SEP-786 or placebo (up to 40 participants total) in 1 of the 4 treatment cohorts. The dose range for SEP-786 will be between 20 and 80 mg.

Part 3 will evaluate twice-daily MAD of SEP-786 from Day 1 through 5. It will consist of a maximum of 3 cohorts and each cohort will consist of up to 10 healthy participants. Participants will be randomized to SEP-786 or placebo (up to 30 participants total) in 1 of the 3 treatment cohorts. The dose range for SEP-786 will be between 10 and 30 mg.

Sentinel dosing will be used in the Part 1 treatment cohorts (SAD) to evaluate acute post-dosing effects in each arm. Before initiating a new dosing arm, Safety Review Committee will review all available safety, tolerability, and pharmacodynamic (PD), data collected in the previous treatment cohorts. For SAD arms, the data will be assessed through at least Day 4, and for MAD arms, up to at least Day 8. Participants will be closely monitored in the clinical research unit (CRU) for safety monitoring.

The study will be conducted at one site in Australia with safety, serum chemistry, pharmacokinetic, and pharmacodynamics parameters monitored for each participant. The anticipated total duration of the study is approximately 9 months.
Intervention code [1] 328916 0
Treatment: Drugs
Comparator / control treatment
Placebo microcrystalline cellulose, white opaque, hydroxypropyl methylcellulose (HPMC) capsules.
Control group
Placebo

Outcomes
Primary outcome [1] 338651 0
Part 1, 2 and 3- Incidence of treatment-emergent adverse events (TEAEs)
Timepoint [1] 338651 0
Part 1, 2 and 3- From study treatment start up to early discontinuation or end of study (up to 15 days)
Primary outcome [2] 338652 0
Part 1, 2 and 3- Change From Baseline in Serum Chemistry Values
Timepoint [2] 338652 0
Part 1: Baseline, Days 1, 2, 3, 4, and 9 post-dose; Part 2 and 3: Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, and 15 post-dose
Primary outcome [3] 338653 0
Part 1, 2 and 3- Change From Baseline in Hematology Parameters
Timepoint [3] 338653 0
Part 1: Baseline, Days 1, 2, 3, 4, and 9 post-dose; Part 2 and 3: Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, and 15 post-dose
Secondary outcome [1] 436842 0
Part 1, 2 and 3- Assessment of pharmacokinetics (PK) parameters: Cmax, Tmax, AUCt, AUC0-inf, t1/2, CL/F, Vz/F
Timepoint [1] 436842 0
Part 1, Day 1: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 10-, 12-, 16-, 24-, 48-, and 72- hours post-dose; Part 2, Day 1: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 12- hours post-dose, Day 2 to 4: 0- (pre-dose) and 8- hours post-dose and Day 5: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 12-, 24-, 36-, 48-, and 72- hours post-dose: Part 3, Day 1: - (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 16- hours post-dose, Day 5: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 10-, 12-, 16-, 24-hours post-dose
Secondary outcome [2] 436843 0
Part 1, 2 and 3- Ae: Amount of SEP-786 Excreted in Urine
Timepoint [2] 436843 0
Part 1: Days 1, 2, 3 and 4 post-dose; Part 2 and 3: Days 5, 6, 7 and 8 post-dose
Secondary outcome [3] 436844 0
Part 1, 2 and 3- Rmax: Rate of SEP-786 Excretion in Urine
Timepoint [3] 436844 0
Part 1: Days 1, 2, 3 and 4 post-dose; Part 2 and 3: Days 5, 6, 7 and 8 post-dose
Secondary outcome [4] 436845 0
Part 1, 2 and 3- CLR: Mean Renal Clearance
Timepoint [4] 436845 0
Part 1: Days 1, 2, 3 and 4 post-dose; Part 2 and 3: Days 5, 6, 7 and 8 post-dose
Secondary outcome [5] 436847 0
Parts 1, 2 and 3- Emax: Maximum Effect of SEP-786 on Albumin-adjusted Serum Calcium following Single and Multiple Doses
Timepoint [5] 436847 0
Part 1, Day 1: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 10-, 12-, 16-, 24-, 48-, and 72- hours post-dose; Part 2, Day 1: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 12- hours post-dose, Day 2 to 4: 0- (pre-dose) and 8- hours post-dose and Day 5: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 12-, 24-, 36-, 48-, and 72- hours post-dose: Part 3, Day 1: - (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8- hours post-dose, Day 5: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 10-, 12-, 16-, 24-hours post-dose
Secondary outcome [6] 436848 0
Parts 1, 2 and 3- TEmax- Time to Emax for Albumin-adjusted Serum Calcium Following Single and Multiple Doses
Timepoint [6] 436848 0
Part 1, Day 1: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 10-, 12-, 16-, 24-, 48-, and 72- hours post-dose; Part 2, Day 1: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 12- hours post-dose, Day 2 to 4: 0- (pre-dose) and 8- hours post-dose and Day 5: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 12-, 24-, 36-, 48-, and 72- hours post-dose: Part 3, Day 1: - (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8- hours post-dose, Day 5: 0- (pre-dose), 0.5-, 1-, 2-, 3-, 4-, 6-, 8-, 10-, 12-, 16-, 24-hours post-dose

Eligibility
Key inclusion criteria
1. Are 24 through 55 years of age, inclusive, at the time of signing the informed consent
2. Are overtly healthy, as determined by medical evaluation, including medical history, physical examinations, laboratory profiles, vital signs, and 12 lead ECGs
3. Have clinical laboratory test values within the normal range, unless assessed by the investigator or designee as a clinically nonsignificant value, with repeat laboratory tests permitted if necessary to make decisions
4. Have a body weight within the range of greater than or equal to (>=) 50 kilogram (kg) and less than or equal to (<=) 90 kg and body mass index (BMI) within the range of >=18.5 to <=27.0 kilogram per square meter (kg/m^2)
5. Have an estimated glomerular filtration rate (eGFR) >=90 milliliter per minute (mL/min)
Note: eGFR is estimated by the chronic kidney disease epidemiology collaboration (CKD EPI) equation
6. Have a QT interval corrected by Fridericia’s method (QTcF) <=450 millisecond (ms) for assigned male at birth (AMAB) participants and <=470 ms for assigned female at birth (AFAB) participants at screening
7. Have inorganic phosphorus and/or serum calcium (albumin corrected) within normal limits at screening and Day -2, unless assessed by the investigator as a clinically insignificant value
8. Are willing and able to abstain from drug, alcohol, and tobacco from Day -2 until discharge from the clinical research unit (CRU)
9. Have negative urine drug and breath alcohol results at screening and Day -2
Minimum age
24 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Have a history or presence of any of the following:
a. Malignant disease, other than basal cell epithelioma/carcinoma or completely resected squamous skin cancer with no recurrence for 12 months
b. Diabetes mellitus
Note: a history of gestational diabetes that is fully resolved is permitted.
c. Hyperparathyroidism, hypoparathyroidism, hypercalcemia, hypercalciuria, kidney stones, familial benign hypocalciuric hypercalcemia, osteomalacia, Paget’s disease, osteoporosis, or any type of metabolic bone disease or radiation therapy to the skeleton
d. Cardiac dysfunction, including abnormal echocardiogram left ventricular ejection fraction (LVEF) <50%, congestive heart failure, long QT syndrome, valvular heart disease except clinically insignificant mitral valve prolapse, hypertrophic cardiomyopathy, or cardiovascular disease
e. Cerebrovascular disease
f. Thromboembolic events or ischemic heart disease
g. Alcoholism or drug abuse within the past 1 year
Note: Alcohol abuse is considered >14 standard drinks/week in AFAB potential participants and >21 standard drinks/week in AMAB potential participants.
h. Stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs
i. Clinically significant medical or psychiatric condition or disease in the opinion of the principal investigator or designee
j. Hepatitis B (defined as HBsAg reactive) or hepatitis C (defined as HCV antibody–positive) at screening
k. Human immunodeficiency virus (HIV) positive status (participants to be screened for HIV or provide a recent negative test)
2. Have an acute disease state (eg, nausea, vomiting, fever, diarrhea) within 7 days of the first dose of study intervention
3. Have a positive COVID 19 polymerase chain reaction (PCR) test at admission
4. Are unable to refrain from using or anticipate the use of any drug or medical device, including prescription and over the counter (OTC) medications, nutritional or dietary supplements, recreational drugs, herbal preparations, or vitamins, from Day -7 until follow up visit, or as specified below:
a. From Day -28 for significant inhibitors or inducers of CYP enzymes and/or P gp, including St. John’s wort, to discharge from CRU
b. From Day -42 for PPIs, supplements containing calcium (Ca) or magnesium (Mg) (including Tums®), and H2 antagonists until discharge from CRU
Exceptions:
a. Acetaminophen, which may be used at doses of 1 gram or less per day until 24 hours prior to check in
b. OTC nonsteroidal anti inflammatory drug (NSAIDs), which may be used until 24 hours prior to check in
c. OCPs or an intrauterine device (IUD) or intrauterine hormone releasing system (IUS)
d. Any drug approved by the medical monitor
5. Have participated in another clinical study within 28 days prior to the first dose of study drug or at least 5.5 half lives, based on the t1/2 for the investigational drug, whichever is longer. The 28 day window is derived from date of the previous study’s last scheduled blood collection or dosing, whichever was later, to Day 1 of the current study.
6. Have clinically significant abnormalities on clinical laboratory results (including hematology, chemistry, and urinalysis) at screening and Day -2
7. Have evidence of endocrine alterations of calcium/phosphate/PTH homeostasis at screening
8. Have donated blood within 7 days of the first dose of study intervention or have had significant (ie, >=500 mL) blood loss within 8 weeks of the first dose of study intervention
9. Have used tobacco within 60 days of screening at a rate of >5 units (cigarettes or vaping equivalents)/week
10. Have consumed alcohol within 24 hours of check in
11. Have a known hypersensitivity to the components of the study intervention
12. Are likely to be noncompliant with respect to study conduct
13. Are mentally or legally incapacitated or have significant emotional problems at the time of the screening visit or expect to have any during the conduct of the study
14. Have any other reason that, in the opinion of the investigator or designee, would prevent the participant from completing participation or following the study schedule

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is concealed and involves contacting the holder of the allocation schedule (randomization list), who is an unblinded pharmacist at the site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/08/2024
Actual
Date of last participant enrolment
Anticipated
9/05/2025
Actual
Date of last data collection
Anticipated
23/05/2025
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 316795 0
Commercial sector/Industry
Name [1] 316795 0
Septerna, Inc.
Country [1] 316795 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Septerna, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 319017 0
None
Name [1] 319017 0
Address [1] 319017 0
Country [1] 319017 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 315564 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315564 0
https://www.alfredhealth.org.au/research/ethics-research-governance
Ethics committee country [1] 315564 0
Australia
Date submitted for ethics approval [1] 315564 0
24/06/2024
Approval date [1] 315564 0
Ethics approval number [1] 315564 0

Summary
Brief summary
The main aim of the study is to evaluate the safety, PK, and PD effects of SEP 786 in healthy participants. The results of this study will help inform the dosing and frequency of dosing in participants with hypoparathyroidism, which is the anticipated main therapeutic use for SEP-786.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135090 0
Dr Chirstina Chang
Address 135090 0
Nucleus Network Pty Ltd. Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 135090 0
Australia
Phone 135090 0
+61 03 8593 9801
Fax 135090 0
Email 135090 0
[email protected]
Contact person for public queries
Name 135091 0
Nucleus Network Melbourne
Address 135091 0
Nucleus Network Melbourne, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 135091 0
Australia
Phone 135091 0
+61 1800 243 733
Fax 135091 0
Email 135091 0
[email protected]
Contact person for scientific queries
Name 135092 0
Nucleus Network Melbourne
Address 135092 0
Nucleus Network Melbourne, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 135092 0
Australia
Phone 135092 0
+61 1800 243 733
Fax 135092 0
Email 135092 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

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No documents have been uploaded by study researchers.

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No additional documents have been identified.