Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000322538
Ethics application status
Approved
Date submitted
8/02/2024
Date registered
25/03/2024
Date last updated
13/04/2024
Date data sharing statement initially provided
25/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1b/2a Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Evaluate Efficacy, Safety, Tolerability and the Pharmacokinetics of GL0034 (Utreglutide) in the Treatment of Non-alcoholic Fatty Liver Disease
Scientific title
A Phase 1b/2a Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Evaluate Efficacy, Safety, Tolerability and the Pharmacokinetics of GL0034 (Utreglutide) in the Treatment of Non-alcoholic Fatty Liver Disease
Secondary ID [1] 311501 0
None
Universal Trial Number (UTN)
None
Trial acronym
SF-CSP-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-alcoholic Fatty Liver Disease (NAFLD) 332832 0
Condition category
Condition code
Metabolic and Endocrine 329549 329549 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomized, double-blind, placebo controlled and parallel group study of GL0034 (Utreglutide) for the treatment of Non-alcoholic Fatty Liver Disease (NAFLD).

Approximately 48 participants will be randomly assigned to receive GL0034/Placebo in a ratio of 3:1. GL0034/Placebo is administered weekly as a subcutaneous injection given by a registered nurse for a period of 13 weeks, The dose will be increased gradually starting at 0.4mg for a period of 2 weeks, 0.8mg for 4 weeks, 1.6mg for 4 weeks (called the Dose Titration Period) and then will remain at a fixed dose of 2.4mg for 3 weeks (called the Final Dose Period).

Vital signs including temperature, blood pressure and weight will be regularly reviewed in addition to the collection of blood tests every 2-4 weeks to assess overall health and any study drug effects. Blood samples will also be collected prior to dosing at visit weeks 1, 3, 5, 6, 9, 10, 12, 13 and 17 to measure the levels of GL0034 in the blood.

If you are eligible for the main study, you may consent to the optional sub-study. The optional sub-study includes additional samples that measure the level of GL0034 in the blood will be collected daily over a period of 5 days at visits week 3, week 7, week 11 and week 13. Blood samples will also be collected once only at week 14, week 15 and week 16.
Intervention code [1] 327949 0
Treatment: Drugs
Comparator / control treatment
Placebo subcutaneous injection. The placebo contains inactive commonly used excipients Disodium Phosphate Dihydrate, Propylene Glycol, Phenol, Hydrochloric Acid and Sodium Hydroxide.
Control group
Placebo

Outcomes
Primary outcome [1] 337342 0
Liver fat content
Timepoint [1] 337342 0
Baseline and at Week 14 (following 13 weeks of treatment)
Secondary outcome [1] 431512 0
Percentage change in liver fat content
Timepoint [1] 431512 0
Baseline and Week 14 (after 13 weeks of treatment)
Secondary outcome [2] 431513 0
Incidence and severity of adverse events (AE) and serious AEs (SAE). Very common adverse events (occurring in more than one in then people) include: Nausea, decreased appetite, early satiety (feeling full after eating a small amount of food), vomiting, indigestion, headache, abdominal discomfort, abdominal distension, diarrhoea and weight loss
Timepoint [2] 431513 0
Weekly from Baseline until Week 17 (after 13 weeks of treatment)
Secondary outcome [3] 431515 0
Composite changes in pre-dose GL0034 plasma concentration (all participants) and pre and post-dose GL0034 plasma concentration (optional sub-study participants only)
Timepoint [3] 431515 0
All participants: Week 1, Week 3, Week 5, Week 6, Week 9, Week 10, Week 12, Week 13 and Week 15 (post-implementation).

Optional sub-study participants: The listed time points as above as well as additional samples at timepoints Week 3, Week 7, Week 11, Week 13 and Week 14 (post-implementation).
Secondary outcome [4] 431516 0
Changes in concentration of plasma anti-GL0034 antibodies
Timepoint [4] 431516 0
From Baseline to Week 14 (following 13 weeks of treatment) and at End of Study visit
Secondary outcome [5] 431517 0
Determine the effect of GL0034 on body weight
Timepoint [5] 431517 0
From Baseline until Week 14 (after 13 weeks of treatment) and at the End of study visit
Secondary outcome [6] 431518 0
Change in Liver fat content from Baseline to Week 9
Timepoint [6] 431518 0
Baseline and Week 9 post implementation

Eligibility
Key inclusion criteria
1) Male or female aged 18 to 70, inclusive at the time of Screen 1.
2) Able to provide voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures at Screen 1.
3) BMI greater than or equal to 30.0 kg/m2 with weight not exceeding the maximum capacity of the local MRI machine or facility infrastructure as per standard practices inclusive at the time of Screen 1, Screen 2, and Day 1.
4) Controlled attenuated parameter (CAP) greater than or equal to 306 dB/m via fasting FibroScan® assessment at Screen 1.
5) Liver fat content greater than or equal to 10%, as assessed by MRI-PDFF at Screen 2
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) History or previous diagnosis of, or currently experiencing any medical condition that may increase the risk associated with study participation, limit the participants ability to complete the study, or to comply with protocol requirements, or to absorb the IP, or interfere with the interpretation of study results, including:
-Non-NAFLD chronic liver disease.
-Proliferative retinopathy or maculopathy requiring acute treatment
-Current diagnosis of a mental health disorder, as defined by DSM-5 with active suicidal ideation.
- Previous clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions.
-Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, or manifest hypo- or hyperthyroidism.
- Pancreatitis (acute or chronic).
-Any other clinically significant unstable medical condition, or laboratory abnormality which, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
Note: Participants with diet-controlled type-2 diabetes (T2D) who have an HbA1c less than or equal to 8 are permitted in this study.

2) Participants with clinically relevant laboratory abnormalities, as assessed by local laboratory, that in the investigator’s opinion could impact participant safety.

3) History of regular and excessive alcohol consumption exceeding 14 standard drinks/week for female participants or 21 drinks/week for male participants (1 drink is equivalent to 150 mL of wine, 360 mL of beer or 45 mL liquor) within the previous 6 months of informed consent.

4) Evidence or previous diagnosis of the following infections:
-Hepatitis B virus,
-Hepatitis C virus (HCV)
-Human immunodeficiency virus (HIV)
-Acute (current and active) Coronavirus disease 2019 (COVID-19) infection.

5) Unstable or poorly controlled hypertension that in the investigator’s opinion would impact participant safety.

6) Supine 12-lead ECG (average) demonstrating a QTcF interval greater than 450 msec or a QRS interval greater than 120 msec, that in the investigator’s opinion could impact participant safety.

7) Estimated GFR <60 mL/min/1.73m2

8) Participants meeting criteria for contraindication for MRI, including:
-History of severe claustrophobia impacting ability to perform MRI during the study.
-Current implants, devices, objects, or markings within or on the body, containing metal or material not compatible with MRI.
-Unable to lie still or maintain a breath hold for the required period to acquire MRI images (15 to 20 seconds).
-Abdominal girth or weight exceeding the maximum capacity of the local MRI system.

9) Participants taking any prohibited concomitant medication(s) or those unable to switch to permitted concomitant medication(s)
-Systemic treatment with vitamin E in the period from 90 days prior to Screen 2 (topical use is allowed).
- Treatment with drugs with a potential effect on steatosis; corticosteroids (topical and inhaled are allowed), methotrexate, tamoxifen, valproic acid, amiodarone or tetracycline in the period from 28 days prior to Screen 2.
- Treatment with orlistat, zonisamide, topiramate, phentermine, lorcaserin, bupropion and naltrexone alone or in combination, or any other medication that could promote weight loss in the opinion of the investigator in the period from 28 days prior to Screen 2.

10) Intentional weight loss (greater than or equal to 5%) within 1 month prior to Screen. .

11) Whole blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to Screen 1 or during the study until the EOS visit.

12) Treatment with an investigational drug within 180 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational drug.

13) Treatment with GLP-1 analogues or GLP-1 receptor (GLP-1R) analogues, or sodium-glucose cotransporter-2 inhibitors in the period from 90 days prior to Screen 2.

14) History of hypersensitivity reaction to GLP-1 analogues and GLP-1R analogues.

15) Any individuals who are directly involved in the conduct of the study, or family members of these individuals.

16) Participants unwilling to adhere to the following lifestyle restriction during the study (from randomization until EOS Visit):
-Abstain from taking recreational drugs in the period of 30 days prior to first dose.
-Abstain from alcohol intake 24 hours prior to each IP product administration.
-8-hour overnight fast (except water) prior to any fasting blood collections.
-Abstain from caffeine-containing products for 2 hours prior to ECG and vital sign measurements.
-Abstain from the use of tobacco or nicotine containing products for 24 hours prior to IP administration.
-Abstain from strenuous exercise (eg, heavy lifting, weight training) for at least 24 hours prior to each blood collection for clinical laboratory tests.

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)
Central randomisation by computer
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 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2024
Actual
28/03/2024
Date of last participant enrolment
Anticipated
4/11/2024
Actual
Date of last data collection
Anticipated
6/01/2025
Actual
Sample size
Target
48
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 315791 0
Commercial sector/Industry
Name [1] 315791 0
Sun Pharmaceuticals Ltd.
Country [1] 315791 0
India
Primary sponsor type
Commercial sector/Industry
Name
International Sponsor: Sun Pharmaceutical Industries Ltd
Address
Country
India
Secondary sponsor category [1] 317915 0
Commercial sector/Industry
Name [1] 317915 0
Local Sponsor: CRO Services Pty Ltd (Trading as Resonance Clinical)
Address [1] 317915 0
Country [1] 317915 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314649 0
Bellberry Human Research Ethics Committee G
Ethics committee address [1] 314649 0
https://bellberry.com.au/
Ethics committee country [1] 314649 0
Australia
Date submitted for ethics approval [1] 314649 0
20/12/2023
Approval date [1] 314649 0
06/02/2024
Ethics approval number [1] 314649 0

Summary
Brief summary
The purpose of this study is to test the safety and effectiveness of the investigational medication in the threatment of Non-alcoholic Fatty Liver Disease (NAFLD) in obese adults. This is a randomized, double-blind, placebo controlled and parallel group study of GL0034 (Utreglutide) for the treatment of (NAFLD).

Approximately 48 participants will be randomly assigned to receive GL0034/Placebo in a ratio of 3:1. GL0034/Placebo is administered weekly as a subcutaneous injection for a period of 13 weeks, The dose will be increased gradually for a period of 10 weeks (called the Dose Titration Period) and then will remain at a fixed dose for 3 weeks (called the Final Dose Period)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132278 0
Prof John Olynyk
Address 132278 0
TrialsWest Pty Ltd, 6 Barrington Street, Spearwood WA 6163
Country 132278 0
Australia
Phone 132278 0
+61 08 9312 1931
Fax 132278 0
Email 132278 0
[email protected]
Contact person for public queries
Name 132279 0
Naomi Brook
Address 132279 0
Resonance Health 141 Burswood Road, Burswood Western Australia 6100
Country 132279 0
Australia
Phone 132279 0
+61 08 9286 5300
Fax 132279 0
Email 132279 0
[email protected]
Contact person for scientific queries
Name 132280 0
Naomi Brook
Address 132280 0
Resonance Health 141 Burswood Road, Burswood Western Australia 6100
Country 132280 0
Australia
Phone 132280 0
+61 08 9286 5300
Fax 132280 0
Email 132280 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
Intellectual Property


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.