Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000887471
Ethics application status
Approved
Date submitted
22/07/2025
Date registered
15/08/2025
Date last updated
15/08/2025
Date data sharing statement initially provided
15/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to evaluate the Safety and Early Effects of Tinodasertib in People who are overweight or Have Obesity.
Scientific title
A Phase Ib, Double-Blind, Randomised, Placebo-Controlled, Parallel Design, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Tinodasertib Monotherapy in Subjects with Obesity or who are Overweight.
Secondary ID [1] 314863 0
None
Universal Trial Number (UTN)
KAR-001-2501
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 338138 0
Condition category
Condition code
Metabolic and Endocrine 334421 334421 0 0
Metabolic disorders
Diet and Nutrition 334653 334653 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a Phase 1b, single center, randomised, placebo-controlled, double-blind, parallel design study to assess the safety and tolerability of 3 doses of tinodasertib administered daily orally compared with placebo for weight management in subjects who have obesity or are overweight with at least one obesity-related comorbidity. Subjects are randomized in a 1::1::1::1 ratio into placebo and 3 different test dose arms. (10mg, 20mg and 30 mg). All subjects will receive diet and physical activity counselling using a standardized approach throughout the study. The study encompasses a 3-week screening period including a screening visit to assess eligibility, followed by a randomization visit and subsequently a 12-week treatment period concluded with a 3 week follow/up period. During screening the participant will be asked about their level of daily activity, their medical history and any concomitant medication. A full Physical examination including height and weight measurement will be done as well as a blood draw and urine sample for routine lab tests including blood for biomarker testing. The participant will complete a health questionnaire and perform a stair climbing test. The total time for screening is approximately 2 hours and will determine if the participant is suitable for the study and to continue to be enrolled. The tests may be done over several clinic visits. The test medicine will be administered orally daily at one of the three low doses and will be compared to a matching blinded placebo. The Test medicine is provided as 24 capsule bottles sufficient for 3 weeks at week 3, 6 and 9. Accountability is performed for the returned capsules during each visit in addition to weekly diary reviews.
Intervention code [1] 331463 0
Treatment: Drugs
Comparator / control treatment
Placebo administered orally daily as matching capsule to active intervention. The placebo consists of Size 1 Swedish orange opaque Vcaps® filled with microcrystalline cellulose (Avicel® PH 200). It contains no active ingredient and is visually identical to the active treatment for use as a control in the clinical trial.
Control group
Placebo

Outcomes
Primary outcome [1] 342121 0
To determine the safety and tolerability of tinodasertib when administered to an obese or overweight subject population assessed as a composite outcome.
Timepoint [1] 342121 0
From Baseline throughout the 12 week treatment and subsequent 3 weeks follow/up period.
Secondary outcome [1] 449608 0
To determine the effects of tinodasertib on body weight, BMI and waist circumference assessed as a composite outcome
Timepoint [1] 449608 0
Baseline and weekly for 4 weeks followed by measurements every 3 weeks until 15 weeks post randomization.
Secondary outcome [2] 449609 0
To determine the effects of tinodasertib doses on metabolic rate
Timepoint [2] 449609 0
Baseline and 12 weeks post randomization.
Secondary outcome [3] 449610 0
To determine the effects of tinodasertib on changes in fat and muscle distribution/composition assessed as a composite outcome
Timepoint [3] 449610 0
Baseline and12 weeks post randomization
Secondary outcome [4] 449611 0
To determine the effects of tinodasertib doses on muscle size and strength assessed as composite outcome
Timepoint [4] 449611 0
Baseline, week 3, 6, 9, 12 and 15 post randomization
Secondary outcome [5] 449612 0
To determine the body weight change in obese and overweight subjects
Timepoint [5] 449612 0
Baseline and weekly until 3 weeks after last treatment
Secondary outcome [6] 449613 0
To characterize the PK profile of tinodasertib in obese and overweight subjects
Timepoint [6] 449613 0
Baseline, week 3, 6, 9 and 12 after randomization

Eligibility
Key inclusion criteria
1. Obese or overweight with the presence of at least one comorbidity (treated or untreated)

And a medical history of at least one self-reported unsuccessful dietary effort to lose body weight
2.. Women of childbearing women must have neg pregnancy test and agree to use contraception/abstinence or be postmenopausal.
3. Male subjects: sterilized or use contraception/abstinence
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has received/taken an approved or experimental weight loss medication within the past 3 months prior to screening
2. Subject undertook any therapy intended for weight management within the past 3 months prior to screening
3. A self-reported change in body weight of more or equal 5% within the last 90 days prior to the screening visit
4. Have prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty within 1 year prior to screening
5. Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months prior to screening
6. Type 1 or type 2 diabetes mellitus or have at least 1 laboratory value suggestive of diabetes during screening, including 1 or more HbA1c more or equal 6.5%, fasting serum glucose higher or equal 126mg/gl, or random glucose higher or equal 200mg/dl or received treatment with glucose-lowering agent(s) within 90 days prior to screening
7. Uncontrolled thyroid disease, defined as TSH higher than 6.0mIU/l or 0.35mIU/l as measured at screening
8. Have renal impairment measures as eGFR < 30ml/min/1.73m2, calculated by the CKD-EPI equation
9. Have a known clinically significant gastric emptying abnormality (eg Severe gastroparesis, or gastric outlet obstruction) in the last 3 months prior to screening or chronically take drugs that directly affect GI motility.
10. History of major depressive disorder within 2 years or diagnosis of other severe psychiatric disorders
11. Have obesity induced by other endocrinologic disorders (eg Cushing's syndrome) or diagnosed monogenetic or syndromic forms of obesity (eg Melanocortin 4 receptor deficiency or Prader Will syndrome)
12. Significant systemic diseases affecting muscle function, including but not limited to
- Endocrine disorders
- Renal failure or significant electrolyte imbalances affecting muscle function
- Chronic steroid use or other medications known to cause muscle atrophy or weakness
13. Ongoing or history of frequent intermittent or chronic tachyarrhytmia syndromes

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)
Numbered capsule bottles
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
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
Statistical methods / analysis
Data of 64 participants (16 per group) will be summarized using descriptive statistics (number of subjects, mean, median, standard deviation, minimum, and maximum) for continuous variables, using frequencies and percentages for discrete variables. Data will be presented by dose group. The study is not powered to determine efficacy, and the tests of the secondary endpoints are to support hypothesis testing in later phase studies. Differences in weight change between each dose group and the control group will be analyzed using one-way analysis of covariance (ANCOVA). Differences in the number of subjects in each group and the control group who have a 5% or greater loss of body weight will be analyzed by Pearson’s Chi-Squared Test.
16 participants per group are required (total 64 subjects), assuming the active arms achieve at least 70% of subjects with a weight loss of more or equal 5% and the reference arm achieves 10% or lower of subjects with a 5%or greater weight loss (both in patients with BMI over or equal 30 kg/m2 and 18 years of age and older, The study will be sufficiently powered at 80% and a two-sided significance level (alpha) of 0.05. Each treatment arm will be tested sequentially against the reference drug alone.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
19/08/2025
Actual
Date of last participant enrolment
Anticipated
3/10/2025
Actual
Date of last data collection
Anticipated
27/02/2026
Actual
Sample size
Target
64
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 319421 0
Commercial sector/Industry
Name [1] 319421 0
Karyogen
Country [1] 319421 0
Singapore
Primary sponsor type
Commercial sector/Industry
Name
Karyogen
Address
Country
Singapore
Secondary sponsor category [1] 322079 0
Other
Name [1] 322079 0
AUM Biosciences
Address [1] 322079 0
Country [1] 322079 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317992 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 317992 0
Ethics committee country [1] 317992 0
Australia
Date submitted for ethics approval [1] 317992 0
11/04/2025
Approval date [1] 317992 0
20/05/2025
Ethics approval number [1] 317992 0
2025-04-559

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142810 0
Dr Thomas Polasek
Address 142810 0
Fusion Clinical Research, Level 1, 53 The Parade, Norwood, SA 5067
Country 142810 0
Australia
Phone 142810 0
+61870776996
Fax 142810 0
Email 142810 0
[email protected]
Contact person for public queries
Name 142811 0
Thomas Polasek
Address 142811 0
Fusion Clinical Research, Level 1, 53 The Parade, Norwood, SA 5067
Country 142811 0
Australia
Phone 142811 0
+61870776996
Fax 142811 0
Email 142811 0
[email protected]
Contact person for scientific queries
Name 142812 0
John Patava
Address 142812 0
AUM Biosciences,Suite 1, Level 3, 62 Lygon Street, Carlton, South Vic, 3053
Country 142812 0
Australia
Phone 142812 0
+61498071249
Fax 142812 0
Email 142812 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.