A Weight Loss Study Evaluating Subcutaneous Treatment With AZD9550 and AZD6234 in Combination Against Placebo or Each of the Drugs Alone (ASCEND)

A Phase IIb Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of Co-administration of AZD9550 and AZD6234 in Participants Living With Obesity or Overweight With Co-morbidity (ASCEND)

The purpose of this study is to determine whether treatment with AZD9550 when given in combination with AZD6234 as once weekly subcutaneous (SC) injections is superior to placebo or either agent administered as monotherapy for weight loss in participants living with obesity or overweight with at least one weight-related co-morbidity.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity or Overweight
• Intervention / Treatment: Drug: AZD9550; Drug: AZD6234; Drug: Placebo comparator

Detailed Description

This is a Phase IIb, global, randomised, parallel-group, double-blind, placebo-controlled, multi-centre, reduced factorial study designed to evaluate the efficacy, safety and tolerability of treatment with AZD9550 and AZD6234 in combination or as monotherapy in adults who are living with obesity or overweight with at least one of the following weight-related co-morbidities: hypertension, dyslipidemia or obstructive sleep apnoea. The study is composed of a screening period, a treatment period and a follow up period with participants expected to be in the study for approximately 47 weeks. The study will be conducted at around 60 sites and in approximately 7 countries with about, 360 participants will be randomly assigned to study intervention or placebo.

• Study Type: Interventional
• Enrollment (Actual): 377
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Maroochydore, Australia, 4556
    • Research Site
  • Maroubra, Australia, 2035
    • Research Site
  • Norwood, Australia, 5067
    • Research Site
  • St Albans, Australia, 3021
    • Research Site
  • St Leonards, Australia, 2065
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2V 4J2
      • Research Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3T 4G8
      • Research Site
  • Ontario
    • Guelph, Ontario, Canada, N1G 0B4
      • Research Site
    • Hamilton, Ontario, Canada, L8L 5G8
      • Research Site
    • Hamilton, Ontario, Canada, L8J 0B6
      • Research Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • Research Site
    • Stouffville, Ontario, Canada, L4A1H2
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4N 2W2
      • Research Site
• Germany
  • Berlin, Germany, 10787
    • Research Site
  • Essen, Germany, 45136
    • Research Site
  • Falkensee, Germany, 14612
    • Research Site
  • Hamburg, Germany, 22607
    • Research Site
  • Münster, Germany, 48145
    • Research Site
  • Oldenburg, Germany, 23758
    • Research Site
• Japan
  • Chūōku, Japan, 103-0027
    • Research Site
  • Chūōku, Japan, 104-0031
    • Research Site
  • Fukuoka, Japan, 812-0025
    • Research Site
  • Shinjuku-ku, Japan, 160-0008
    • Research Site
  • Suita-shi, Japan, 565-0853
    • Research Site
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Research Site
    • Vestavia Hills, Alabama, United States, 35216
      • Research Site
  • California
    • Cerritos, California, United States, 90703
      • Research Site
    • Escondido, California, United States, 92025
      • Research Site
    • Huntington Park, California, United States, 90255
      • Research Site
    • Lincoln, California, United States, 95648
      • Research Site
    • Sacramento, California, United States, 95864
      • Research Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Research Site
  • Florida
    • Palm Harbor, Florida, United States, 34684
      • Research Site
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Research Site
    • Stockbridge, Georgia, United States, 30281
      • Research Site
  • Illinois
    • Champaign, Illinois, United States, 61822
      • Research Site
  • Indiana
    • South Bend, Indiana, United States, 46617
      • Research Site
    • Valparaiso, Indiana, United States, 46383
      • Research Site
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • Research Site
  • Michigan
    • Southfield, Michigan, United States, 48034
      • Research Site
  • Montana
    • Missoula, Montana, United States, 59804
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87107
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Research Site
    • Columbus, Ohio, United States, 43213
      • Research Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • Research Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Research Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Research Site
  • Texas
    • Brownsville, Texas, United States, 78526
      • Research Site
    • Houston, Texas, United States, 77043
      • Research Site
  • Virginia
    • Arlington, Virginia, United States, 22206
      • Research Site
  • Washington
    • Renton, Washington, United States, 98057
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 18 to 75 years of age inclusive.
• BMI: ≥ 30 kg/m2, or ≥ 27 kg/m2 with at least one weight related comorbidity.
• A stable, self-reported body weight for 3 months prior to screening.
• Male and female participants: Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Female participants must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
• Capable of giving signed informed consent.

Exclusion Criteria:

• History of any clinically important disease or disorder, which, in the opinion of the Investigator, may put the participant at risk.
• History or presence of GI, renal, hepatic disease.
• Previous or planned bariatric surgery or fitting of a weight loss device.
• Obesity induced by endocrine disorders such as Cushing's syndrome, insulinoma or Prader-Willi syndrome.
• History of T1DM or T2DM or symptoms indicative of insulinopenia or poor glucose control.
• HbA1c ≥ 6.5% (48 mmol/mol), fasting serum glucose ≥ 126 mg/dL (7.0 mmol/L) or random glucose ≥ 200 mg/dL (11.1 mmol/L).
• Significant gastric and hepatobiliary disease.
• History of acute or chronic pancreatitis or pancreatic amylase or lipase > 2 × ULN at screening.
• History of psychosis or bipolar disorder.
• History of major depressive disorder within the 2 years prior to screening or depression.
• Treatment with a GLP1 containing preparation, either as part of treatment or while participating in another clinical study within the 3 months or 5 half-lives of the drug prior to screening.
• Vulnerable populations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; AZD9550 low dose + AZD6234 low dose or placebos	Drug: AZD9550; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP; Drug: AZD6234; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP.; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.
Experimental: Arm 2; AZD9550 medium dose + AZD6234 medium dose or placebos	Drug: AZD9550; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP; Drug: AZD6234; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP.; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.
Experimental: Arm 3; AZD9550 high dose + AZD6234 high dose or placebos	Drug: AZD9550; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP; Drug: AZD6234; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP.; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.
Experimental: Arm 4; AZD9550 low dose + AZD6234 medium dose or placebos	Drug: AZD9550; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP; Drug: AZD6234; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP.; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.
Experimental: Arm 5; AZD9550 medium dose + AZD6234 low dose or placebos	Drug: AZD9550; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP; Drug: AZD6234; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP.; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.
Experimental: Arm 6; AZD9550 high dose + AZD6234 medium dose or placebos	Drug: AZD9550; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP; Drug: AZD6234; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP.; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.
Experimental: Arm 7; AZD9550 medium dose + AZD6234 high dose or placebos	Drug: AZD9550; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP; Drug: AZD6234; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP.; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.
Experimental: Arm 8; AZD9550 high dose or placebo	Drug: AZD9550; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.
Experimental: Arm 9; AZD6234 high dose or placebo	Drug: AZD6234; IMP injected subcutaneous, once weekly. Unit dose strength as per CSP.; Drug: Placebo comparator; Placebo matching IMP dose injected subcutaneously, once weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in body weight from baseline after 36 weeks of treatment	To determine whether treatment with AZD9550 and AZD6234 in combination is superior to placebo for weight loss	36 weeks
Weight loss ≥ 5% from baseline after 36 weeks of treatment	To assess the effect of treatment with AZD9550 and AZD6234 in combination vs placebo on the proportion of participants with weight loss ≥ 5%	36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in body weight from baseline after 36 weeks of treatment	To determine whether treatment with AZD9550 and AZD6234 in combination is superior to placebo for weight loss	36 weeks
Prevalence of ADAs to AZD9550 and AZD6234 in combination and as monotherapies after 36 weeks of treatment	To assess the immunogenicity profile of treatment with AZD9550 and AZD6234 in combination and as monotherapies	36 weeks
Titres of ADAs to AZD9550 and AZD6234 in combination and as monotherapies after 36 weeks of treatment	To assess the immunogenicity profile of treatment with AZD9550 and AZD6234 in combination and as monotherapies	36 weeks
Absolute change in body weight from baseline after 36 weeks of treatment	To determine whether treatment with AZD9550 and AZD6234 in combination is superior to AZD9550 and AZD6234 monotherapy, and whether AZD9550 and AZD6234 as monotherapies are superior to placebo for weight loss	36 weeks
Weight loss ≥ 5% from baseline after 36 weeks of treatment	To assess the effect of treatment with AZD9550 and AZD6234 in combination vs monotherapy, and assess the effect of AZD9550 and AZD6234 as monotherapies vs placebo, on the proportion of participants with weight loss ≥ 5%	36 weeks
Weight loss ≥ 10% and ≥ 15% from baseline after 36 weeks of treatment	To assess the effect of treatment with AZD9550 and AZD6234 in combination vs placebo and monotherapy, and assess the effect of AZD9550 and AZD6234 as monotherapies vs placebo, on the proportion of participants with weight loss ≥ 10% and ≥ 15%	36 weeks
Incidence of ADAs to AZD9550 and AZD6234 in combination and as monotherapies after 36 weeks of treatment	To assess immunogenicity profile of ADAs to AZD9550 and AZD6234 in combination and as monotherapies	36 weeks
Percent change in body weight from baseline after 36 weeks of treatment	To determine whether treatment with AZD9550 and AZD6234 in combination is superior to AZD9550 and AZD6234 monotherapy, and whether AZD9550 and AZD6234 as monotherapies are superior to placebo for weight loss	36 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• 20260129-draft-structured-data-ascend-sm-04-de

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2025
• Primary Completion (Estimated): May 25, 2026
• Study Completion (Estimated): May 25, 2026

Study Registration Dates

• First Submitted: February 14, 2025
• First Submitted That Met QC Criteria: March 4, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Overweight; AZD9550; AZD6234
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: D8460C00004; 2024-516176-15-00 (Registry Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request 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.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No