A Trial to Learn How Safe AZD9550 Monotherapy and Combined With AZD6234 is in People With or Without Type 2 Diabetes Who Are Living With Obesity and Overweight

NCT06151964 | Active Not Recruiting Phase 1

• 2 other identifiers: D8460C000022023-504215-32-00
• Study Type: interventional
• Target: 118
• Locations: 5 countries
• Sites: 15

Brief Summary

AZD9550, previously being developed for the treatment NASH, is a dual GCG and GLP-1 receptor agonist. AZD9550 is now being developed in combination with AZD6234, a SARA, for the treatment of overweight and obesity and its associated co-morbidities. Co-administration of AZD9550 and AZD6234 is currently being evaluated in participants living with obesity and overweight without T2DM in an ongoing Phase 2b study. The purpose of this study is to investigate the safety, tolerability, and effects of increasing doses of AZD9550 monotherapy in overweight and obese participants aged 18 through 65 years living with or without T2DM, and to investigate how AZD9550 is absorbed, distributed, and eliminated from the body (Parts A-D). In addition, the study will investigate the safety and tolerability of co-administration of AZD9550 and AZD6234 in participants living with T2DM with obesity or overweight aged 18 through 75 years (Part E).

Conditions

Overweight and Obesity

Keywords

AZD9550; AZD6234; Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis; Overweight; Obese; Obesity; Diabetes Mellitus, Type 2; Liver Glycogen; Adipose Tissue; Glucose; 3-Hydroxybutyric Acid; Subcutaneous Fat; Liver fat; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Weight Loss; Mixed Meal Tolerance Test

Outcome Measures

Primary Outcomes (12)

• Number and percentage of participants with any AE, SAEs, AEs leading to discontinuation of study intervention, AEs with outcome of death, and AEs leading to withdrawal from study.

  Applicable for Parts A, B, C, D, E.

  Day - 35 to Day 205

• Number and percentage of participants with clinically significant changes from baseline in Vital Sign Parameters.

  Applicable for Parts A, B, C, D, E.

  Day - 35 to Day 205

• Number and percentage of participants with clinically significant changes in ECG parameters.

  Applicable for Parts A, B, C, D, E.

  Day - 35 to Day 205

• Number and percentage of participants with clinically significant changes from baseline in Clinical Laboratory Parameters

  Applicable for Parts A, B, C, D, E.

  Day - 35 to Day 205

• Area Under Concentration-Time Curve of AZD9550 following repeat weekly SC doses

  * AUC from 0 to the time of the last measured concentration (AUClast) at first dose and last dose * AUC over a dosing interval (AUCtau) at first dose and last dose. Applicable for Part A.

  Day 1 to Day 65

• Maximum observed concentration of AZD9550 following repeat weekly SC doses

  • Cmax at first dose and last dose Applicable for Part A.

  Day 1 to Day 65

• Half life associated with terminal phase elimination rate constant of AZD9550 following repeat weekly SC doses

  • t1/2λz at first dose and last dose Applicable for Part A.

  Day 1 to Day 65

• Time to maximum observed concentration of AZD9550 following repeat weekly SC doses

  • tmax at first dose and last dose Applicable for Part A.

  Day 1 to Day 65

• Apparent oral clearance of AZD9550 following repeat weekly SC doses

  • CL/F at first dose and last dose Applicable for Part A.

  Day 1 to Day 65

• Apparent volume of distribution of AZD9550 following repeat weekly SC doses

  • Vz/F at first dose and last dose Applicable for Part A.

  Day 1 to Day 65

• Ratio for AUC of AZD9550 following repeat weekly SC doses

  • Rac AUCtau at last dose Applicable for Part A.

  Day 1 to Day 65

• Ratio for Cmax of AZD9550 following repeat weekly SC doses

  • Rac Cmax at last dose Applicable for Part A.

  Day 1 to Day 65

Secondary Outcomes (70)

• PD effect of AZD9550 on fasting glucose compared to placebo

  From baseline to Week 4

• PD effect of AZD9550 on fasting lipid profile compared to placebo

  From baseline to Week 4

• Absolute and percentage change in body weight from baseline

  From baseline to Week 4

• Incidence of anti-AZD9550 antibodies

  From Day 1 to Day 65

• Absolute change in percentage body fat from baseline

  From baseline to Week 4

Study Arms (10)

Part A: AZD9550

EXPERIMENTAL

Multiple repeat doses of AZD9550 given as 4 once weekly SC doses for 4 weeks to 2 sequential cohorts in overweight/obese participants with or without T2DM, evaluating 2 low dose levels of AZD9550

Drug: AZD9550

Part B: AZD9550

EXPERIMENTAL

Once weekly up-titration over 5 doses of AZD9550 in overweight/obese participants with or without T2DM

Drug: AZD9550

Part C: AZD9550

EXPERIMENTAL

Bi-weekly/monthly up-titration of AZD9550 for 24 weeks in overweight/obese participants with or without T2DM.

Drug: AZD9550

Part D: AZD9550

EXPERIMENTAL

Bi-weekly/monthly up-titration of AZD9550 for 24 weeks in overweight/obese Japanese participants with T2DM.

Drug: AZD9550

Part A: placebo

EXPERIMENTAL

Multiple repeat doses of placebo given as 4 once weekly SC doses for 4 weeks to 2 sequential cohorts in overweight/obese participants with or without T2DM, evaluating 2 low dose levels of AZD9550

Drug: Placebo

Part B: placebo

EXPERIMENTAL

Once weekly administration of placebo over 5 doses, volume matched to the active treatment being up-titrated, in overweight/obese participants with or without T2DM

Drug: Placebo

Part C: placebo

EXPERIMENTAL

Bi-weekly/monthly administration of placebo - volume matched to the active treatment being up-titrated - for 24 weeks in overweight/obese participants with or without T2DM.

Drug: Placebo

Part D: placebo

EXPERIMENTAL

Bi-weekly/monthly administration of placebo - volume matched to the active treatment being up-titrated - 24 weeks in overweight/obese Japanese participants with T2DM.

Drug: Placebo

Part E: AZD9550 and AZD6234

EXPERIMENTAL

Bi-weekly/monthly up-titration of AZD9550 and AZD6234 for 24 weeks in overweight/obese participants with T2DM.

Drug: AZD9550 and AZD6234

Part E: Placebo

EXPERIMENTAL

Bi-weekly/monthly administration of placebo - volume matched to the active treatments being up-titrated - 24 weeks inoverweight/obese participants with T2DM.

Drug: Placebo

Interventions

AZD9550 DRUG

Part A: A constant dose Part B: Doses of AZD9550 that increase each week Part C: Doses of AZD9550 that increase every 2 weeks, then every 4 weeks Part D: Doses of AZD9550 that increase every 2 weeks, then every 4 weeks

Part A: AZD9550; Part B: AZD9550; Part C: AZD9550; Part D: AZD9550

Placebo DRUG

Matching administration volumes for SC injection

Part A: placebo; Part B: placebo; Part C: placebo; Part D: placebo; Part E: Placebo

AZD9550 and AZD6234 DRUG

Part E: Doses of AZD9550 and AZD6234 that increase every 2 weeks, then every 4 weeks

Part E: AZD9550 and AZD6234

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged 18 through 65 years (Parts A-D) or 75 years (Part E) at the time of screening.
• Parts A, B, C only: Participants with or without T2DM. If participants have a diagnosis of T2DM, the glucose control managed with diabetes diet and in addition to metformin treatment no more than two treatment options (with a stable dose 3 months prior to screening).
• Part D only: Participants who are diagnosed with T2DM, have inadequate glycaemic control with diet and exercise. Participants who are prescribed an oral anti-diabetic agent such as metformin, a DPP IV inhibitor, sulphonylurea, glinides, alphaglucosidase inhibitors, and an SGLT2 inhibitor may be eligible to enter the study following a washout of 4-weeks or 5-half lives (whichever is longer) washout period.
• Part E only: Participants are eligible to be included in the Part E only if they meet all of the following criteria at screening:
• Diagnosed with T2DM.
• Are treated with diet and exercise only, or any combination of OAD with stable doses in the 3 months prior to dosing.
• Participants prescribed a DPP IV inhibitor or a GLP-1RA-containing medicine, alone or in combination with other OADs, may be eligible to enter the study if they have not been treated with any of these drugs for at least 35 days or 5 drug half-lives (whichever is longer) prior to randomisation.
• Participants with a screening HbA1c value within the target range of
• ≥ 42 to ≤ 86 mmol/mol (6% to 10%).
• Body mass index from ≥27 (≥25 in Part D) to ≤39.9 kg/m2 (inclusive) (Part A-D) or ≥ 27 kg/m2 (Part E).
• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Written informed consent and any locally required authorization (eg, European Union Data Privacy Directive) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations
• Ability to complete and meet all eligibility requirements for randomisation within 60 days after signing the ICF.
• Venous access suitable for multiple cannulations.
• Willing and able to self-administer weekly SC injections (Parts C, D and E only).

You may not qualify if:

• Participants with T2DM treated with insulin.
• Participants with T2DM treated with more than 3 anti-diabetic therapies (Parts A-D only).
• Participants with or without T2DM treated with a GLP-1RA or GLP-1RA/GIPRA within 3 months of screening (Parts A to D only) or within 35 days of randomisation or five half-lives (whichever is shorter) of dosing (Part E only).
• History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• Serum calcitonin suggestive of thyroid C-cell hyperplasia (calcitonin level \> 50 ng/L), medullary thyroid carcinoma, or history or family history of multiple endocrine neoplasia at screening.
• History or presence of GI, renal, or hepatic disease (with the exception of Gilbert's syndrome), or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs, as judged by the investigator.
• History of cancer within the last 10 years, with the exception of non-melanoma skin cancer.
• Any clinically important illness (apart from T2DM), as judged by the investigator.
• Any medical/surgical procedure, or trauma within 4 weeks prior to screening, at the discretion of the investigator.
• Symptoms of insulinopenia or poor blood glucose control (eg, significant thirst, nocturia, polyuria, polydipsia, or weight loss).
• Positive hepatitis B or hepatitis C virus serology at screening.
• Positive human immunodeficiency virus test at screening or participant taking antiretroviral medications as determined by medical history or participant's verbal report.
• At screening blood tests, any of the following:
• AST ≥ 1.5 × ULN
• ALT ≥ 1.5 × ULN

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (15)

Research Site

Graz, 8036, Austria

Location

Research Site

Vienna, 1090, Austria

Location

Research Site

Surrey, British Columbia, V3T 2V6, Canada

Location

Research Site

Sarnia, Ontario, N7T 4X3, Canada

Location

Research Site

Stouffville, Ontario, L4A 1H2, Canada

Location

Research Site

Toronto, Ontario, M4G 3E8, Canada

Location

Research Site

Toronto, Ontario, M4J 5B9, Canada

Location

Research Site

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Research Site

Magdeburg, 39120, Germany

Location

Research Site

Neu-Ulm, 89231, Germany

Location

Research Site

Neuss, 41460, Germany

Location

Research Site

Fukuoka, 812-0025, Japan

Location

Research Site

Shinjuku-ku, 160-0004, Japan

Location

Research Site

Suita-shi, 565-0853, Japan

Location

Research Site

Uppsala, 752 37, Sweden

Location

MeSH Terms

Conditions

Overweight; Obesity; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Fatty Liver; Weight Loss

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight Changes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study is single-blind with regard to treatment (AZD9550 monotherapy, co-administered AZD9550 and AZD6234, or placebo). This means that the participant, investigator, Study Monitor, and the clinical unit staff will remain blinded during each part of the study and the randomisation code will only be available at each predefined decision point before the SRC meeting in order to review the data unblinded, if necessary. The sponsor will be unblinded throughout the study. AZD9550, AZD6234, and placebos will as far as possible be matched for appearance and volume. Participants randomised to placebo will receive the same volume of injection (SC cohorts) as participants on active treatment. In Part E, the number of injections per dosing occasion (ie, 2) will be the same in all treatment arms.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will randomise approx. 120 participants and is devided in 5 parts (Part D conducted only in Japan): A: Approx. 45 participants will be screened to achieve 16 randomised. The study duration approx. 103 days. B: Approx. 90 participants will be screened to achieve 30 randomised. The study duration approx. 110 days. C: Approx. 90 participants will be screened to achieve 30 randomised. The study duration approx. 249 days. D: Approx. 35 participants will be screened to achieve 12 randomised. The study duration approx. 249 days. E: Approx. 80 participants will be screened to achieve approx. 28 randomised. The study duration approx. 249 days.

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: November 30, 2023
• Study Start: September 29, 2023
• Primary Completion (Estimated): March 17, 2027
• Study Completion (Estimated): March 17, 2027
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

JP (3); SE (1); CA (6); AU (2); DE (3)