This is a Multi-centre, Multi-drug, Platform Study in Chinese Participants Living With Obesity / Overweight

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: Obesity/Overweight

Treatments: Drug: AZD9550; Drug: Placebo; Drug: AZD6234; Drug: AZD6234 in combination with AZD9550; Drug: Plocebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07017179

D8750C00009

Details and patient eligibility

About

This study is to assess the safety and tolerability, PK characterisation, efficacy, and immunogenicity of the study intervention, and it allows assessment of the monotherapy or combination therapy of AZD6234 and AZD9550 in different sub-studies.

Full description

This is a Phase Ⅱa, multi-centre, multi-drug, platform study in Chinese participants living with obesity/overweight. This platform study will consist of several sub-studies. Eligible participants will be allocated to one sub-study to receive the study intervention(s). Each sub-study will consist of a screening period, a treatment period, and a follow-up period.

Sub-study 1: AZD6234 Monotherapy This study will explore the safety, tolerability, pharmacokinetic (PK), efficacy, and immunogenicity of AZD6234 in Chinese participants with obesity/overweight, approximate 18 participants will be randomised in sub-study 1. The sub-study will comprise 3 periods totalling up to approximately 23 weeks.

Sub-study 2: AZD9550 Monotherapy and AZD6234 in combination with AZD9550 This study will explore the safety, tolerability, PK, efficacy, and immunogenicity of AZD9550 and of AZD6234 in combination with AZD9550 in Chinese participants with obesity/overweight, approximately 30 participants will be randomised in sub-study 2 (15 in Cohort A and 15 in Cohort B). The sub-study will comprise 3 periods totalling up to approximately 35 weeks.

Enrollment: 871 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18 to 55 years.
2. BMI ≥ 27 kg/m2.
3. Stable body weight for 3 months prior to screening.
4. Male and female (Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies).
5. Participants should refrain from blodd donation throughout the sub-study, including the follow-up period.
6. Negative pregnancy test at screening and randomisation for FOCBP and must not be breastfeeding.

Exclusion criteria

1. Have received prescription medication or non-prescription medication for weight loss within the last 3 months prior to screening.

2. History of type 1 or type 2 diabetes mellitus or symptoms indicative of insulinopenia or poor glucose control.

3. Treatment with diabetes medication in past 3 months prior to screening.

4. HbA1c ≥ 6.5% (48 mmol/mol) at screening.

5. Gastroparesis (or similar) requiring treatment.

6. Significant inflammatory bowel disease or other severe disease or surgery affecting the upper GI tract.

7. Significant hepatic disease (except for non-alcoholic steatohepatitis or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results at screening:

   1. AST ≥ 2.5 × ULN
   2. ALT ≥ 2.5 × ULN
   3. TBL ≥ 1.5 × ULN.

8. Prior history of cholecystectomy or untreated cholelithiasis.

9. History of acute or chronic pancreatitis or pancreatic amylase or lipase > 2 × ULN at screening.

10. Severely uncontrolled hypertension defined as systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg on the average of 2 seated measurements after being at rest for at least 5 minutes.

11. HR < 50 bpm or > 100 bpm after being at rest for 5 minutes.

12. Impaired renal function defined as eGFR ≤ 45 mL/minute/1.73 m2 at screening (GFR estimated according to CKD-EPI).

13. History of psychosis or bipolar disorder.

14. Severe vitamin D deficiency defined as a 25-OH vitamin D level < 12 ng/mL.

15. Uncontrolled thyroid disease, defined as TSH > ULN or < LLN for the laboratory reference range, as judged by the PI at screening.

    Sub-study 2 only

16. Personal or family history (first-degree relative) of MTC or MEN2.

17. History of marijuana or THC use within 3 months before screening, or unwilling/unable to abstain from marijuana or THC use during the study.

18. Previous hospitalisation for any psychiatric reason.

19. PHQ-9 score ≥ 15 within the 2 years prior to screening or at screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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871 participants in 6 patient groups, including a placebo group

AZD6234 (sub-study 1)

Experimental group

Description:

Participants will receive subcutaneous injection of AZD6234 on Day 1 and continue for 16 weeks.

Treatment:

Drug: AZD6234

Placebo (sub-study 1)

Placebo Comparator group

Description:

Participants will receive subcutaneous injection of matched volume of placebo on Day 1 and continue for 16 weeks.

Treatment:

Drug: Placebo

Drug: Placebo

AZD9550（sub-study 2 Cohort A)

Experimental group

Description:

Participants will receive subcutaneous injection of AZD9550 on Day 1 and continue for 28 weeks.

Treatment:

Drug: AZD9550

Placebo (sub-study 2 Cohort A)

Placebo Comparator group

Description:

Participants will receive subcutaneous injection of matched volume of placebo on Day 1 and continue for 28 weeks.

Treatment:

Drug: Plocebo

AZD6234 in combination with AZD9550 (sub-study 2 Cohort B)

Experimental group

Description:

Participants will receive subcutaneous injection of AZD6234 and AZD9550 on Day 1 and continue for 28 weeks.

Treatment:

Drug: AZD6234 in combination with AZD9550

Placebo (sub-study 2 Cohort B)

Placebo Comparator group

Description:

Participants will receive subcutaneous injection of matched volume of placebo on Day 1 and continue for 28 weeks.

Treatment:

Drug: Placebo

Drug: Placebo