N-[2-(3-CYANO-5-FLUOROPHENYL)-2-METHYL-1-OXOPROPYL]-BETA-ALANYL-L-ALPHA-GLUTAMYLGLYCYL-L-THREONYL-L-PHENYLALANYL-L-THREONYL-L-SERYL-L-ALPHA-ASPARTYL-L-TYROSYL-L-SERYL-L-ISOLEUCYL-2-METHYLALANYL-L-LEUCYL-L-ALPHA-ASPARTYL-L-LYSYL-L-ISOLEUCYL-L-ALANYL-L-GLUTAMINYL-N6-[N-(19-CARBOXY-1-OXONONADECYL)-L-GAMMA-GLUTAMYL-2-[2-(2-AMINOETHOXY)ETHOXY]ACETYL-2-[2-(2-AMINOETHOXY)ETHOXY]ACETYL]-L-LYSYL-L-ALANYL-L-PHENYLALANYL-L-VALYL-L-GLUTAMINYL-L-TRYPTOPHYL-L-LEUCYL-L-ISOLEUCYL-L-ALANYLGLYCYLGLYCYL-L-PROLYL-L-SERYL-L-SERYLGLYCYL-L-ALANYL-L-PROLYL-L-PROLYL-L-PROLYL-L-SERINAMIDE for Obesity | Overweight

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years at the time of signing Informed Consent Form\n- Ability and willingness to comply with all aspects of the protocol including completion of all procedures, study visits, questionnaires, assessments for the duration of the study\n- Ability and willingness to self-administer the study drug (or receive an injection from a trained individual if visually impaired or with physical limitations)\n- Body mass index (BMI) ≥ 30.0 kg/m2 OR BMI ≥ 27.0 and <30.0 kg/m2 and diagnosed with at least one of the following weight-related comorbidities: – Prediabetes as defined by the 2025 American Diabetes Association (ADA) Standards of Medical Care in Diabetes, i.e., HbA1c 5.7–6.4% (39–47 mmol/mol) or fasting plasma glucose 100–125 mg/dL (5.6–6.9 mmol/L) as determined by laboratory test during screening – Hypertension: defined as current stable use (minimum 4 weeks prior to screening) of blood pressure lowering agents initiated for hypertension, or with systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥ 80 mm Hg during screening – Dyslipidemia: defined as current stable use (minimum 4 weeks prior to screening) of lipid-lowering agents initiated for dyslipidemia, or with low-density lipoprotein (LDL) ≥160 mg/dL (4.1 mmol/L) or triglycerides ≥150 mg/dL (1.7 mmol/L), or high-density lipoprotein (HDL) < 40 mg/dL (1.0 mmol/L) for men or HDL < 50 mg/dL (1.3 mmol/L) for women as determined by laboratory test during screening – Obstructive sleep apnea – Weight-related cardiovascular disease (including, but not limited to, ischemic cardiovascular disease, New York Heart Association (NYHA) Functional Class I-III heart failure)\n- History of ≥ 1 self-reported unsuccessful diet/exercise effort to lose body weight\n- Agreement to adhere to the contraception requirements"}

Exclusion criteria

• {"criterion_text":"- History of Type 1 Diabetes Mellitus (T1DM) or T2DM, or history of ketoacidosis or hyperosmolar state/coma Prior, but not current, diagnosis of gestational diabetes is allowed if no history of diabetes is recorded since.\n- Self-reported change in body weight >5 kg within 3 months prior to screening\n- Obesity induced by other endocrinologic disorders (e.g., Cushing’s syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., melanocortin 4 receptor deficiency or Prader-Willi syndrome)\n- Prior or planned surgical treatment for obesity Liposuction or abdominoplasty if performed more than 1 year prior to screening is allowed.\n- Known clinically significant gastric emptying abnormality (e.g., severe gastroparesis or gastric outlet obstruction)\n- History of acute or chronic pancreatitis or clinically significant gallbladder disease History of acute pancreatitis caused by gallstones or clinically significant gallbladder disease is allowed if the participant had a cholecystectomy to resolve the problem at least 3 months prior to screening."}

Primary endpoints

• {"endpoint_text":"- Percent (%) change from baseline in body weight at Week 72","definition_or_measurement_approach":"Percent change from baseline in body weight measured at Week 72 (percent change calculated from baseline body weight to weight measured at Week 72)."}

Secondary endpoints

• {"endpoint_text":"- Achieve ≥5% body weight loss at Week 72 (Yes/No)","definition_or_measurement_approach":"Proportion of participants achieving ≥5% weight loss from baseline at Week 72 (Yes/No)."}
• {"endpoint_text":"- Achieve ≥10% body weight loss at Week 72 (Yes/No)","definition_or_measurement_approach":"Proportion of participants achieving ≥10% weight loss from baseline at Week 72 (Yes/No)."}
• {"endpoint_text":"- Achieve ≥15% body weight loss at Week 72 (Yes/No)","definition_or_measurement_approach":"Proportion of participants achieving ≥15% weight loss from baseline at Week 72 (Yes/No)."}
• {"endpoint_text":"- Achieve ≥20% body weight loss at Week 72 (Yes/No)","definition_or_measurement_approach":"Proportion of participants achieving ≥20% weight loss from baseline at Week 72 (Yes/No)."}
• {"endpoint_text":"- Achieve ≥25% body weight loss at Week 72 (Yes/No)","definition_or_measurement_approach":"Proportion of participants achieving ≥25% weight loss from baseline at Week 72 (Yes/No)."}
• {"endpoint_text":"- Change from baseline in body weight (kg) at Week 72","definition_or_measurement_approach":"Absolute change in body weight (kg) from baseline to Week 72."}
• {"endpoint_text":"- Change from baseline in waist circumference (cm) at Week 72","definition_or_measurement_approach":"Change in waist circumference (cm) from baseline to Week 72."}
• {"endpoint_text":"- Change from baseline in fasting glucose at Week 72","definition_or_measurement_approach":"Change in fasting plasma glucose from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline in fasting insulin at Week 72","definition_or_measurement_approach":"Change in fasting insulin from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline in LDL cholesterol at Week 72","definition_or_measurement_approach":"Change in LDL cholesterol from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline in HDL cholesterol at Week 72","definition_or_measurement_approach":"Change in HDL cholesterol from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline in triglyceride at Week 72","definition_or_measurement_approach":"Change in triglycerides from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline in systolic blood pressure at Week 72","definition_or_measurement_approach":"Change in systolic blood pressure from baseline to Week 72 measured by vital signs."}
• {"endpoint_text":"- Change from baseline in physical functioning as assessed by physical functioning domain of Short Form (36) Health Survey Version 2 Acute Form (SF-36v2 Acute Form) at Week 72","definition_or_measurement_approach":"Change in SF-36v2 Acute Form physical functioning domain score from baseline to Week 72."}
• {"endpoint_text":"- Change from baseline in physical functioning composite as assessed by Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQoL-Lite-CT) at Week 72","definition_or_measurement_approach":"Change in IWQoL-Lite-CT physical functioning composite score from baseline to Week 72."}
• {"endpoint_text":"- Change from baseline in waist-to-hip ratio at Week 72","definition_or_measurement_approach":"Change in waist-to-hip ratio from baseline to Week 72."}
• {"endpoint_text":"- Change from baseline in waist-to-height ratio at Week 72","definition_or_measurement_approach":"Change in waist-to-height ratio from baseline to Week 72."}
• {"endpoint_text":"- Achieve normoglycemia (hemoglobin A1c (HbA1c) < 5.7%) at Week 72 (Yes/No)","definition_or_measurement_approach":"Proportion of participants achieving HbA1c < 5.7% at Week 72 (Yes/No)."}
• {"endpoint_text":"- Change from baseline in Control of Eating Questionnaire (CoEQ) subscale scores for craving control, positive mood, craving for savory and craving for sweet; and the individual hunger item score at Week 72","definition_or_measurement_approach":"Change in CoEQ subscale and individual hunger item scores from baseline to Week 72."}
• {"endpoint_text":"- Change from baseline on symptoms and impact of urinary incontinence as assessed by International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) at Week 72","definition_or_measurement_approach":"Change in ICIQ-UI SF score from baseline to Week 72."}
• {"endpoint_text":"- Experience no change, improvement, or worsening in Patient Global Impression of Change (PGI-C) Urinary Incontinence at Week 72","definition_or_measurement_approach":"Patient Global Impression of Change (PGI-C) for urinary incontinence at Week 72 (categorical: no change/improvement/worsening)."}
• {"endpoint_text":"- Experience no change, improvement, or worsening in Patient Global Impression of Severity/Status (PGI-S) Urinary Incontinence at Week 72","definition_or_measurement_approach":"Patient Global Impression of Severity/Status (PGI-S) for urinary incontinence at Week 72 (categorical)."}
• {"endpoint_text":"- Experience no change, improvement, or worsening in PGI-C Physical Functioning at Week 72","definition_or_measurement_approach":"PGI-C assessment of physical functioning at Week 72 (categorical: no change/improvement/worsening)."}
• {"endpoint_text":"- Experience no change, improvement, or worsening in PGI-S Physical Functioning at Week 72","definition_or_measurement_approach":"PGI-S assessment of physical functioning at Week 72 (categorical)."}
• {"endpoint_text":"- Change from baseline in HRQoL as assessed by SF-36v2 Acute Form domain scores and component summary scores at Week 72","definition_or_measurement_approach":"Change in SF-36v2 Acute Form domain and summary component scores from baseline to Week 72."}
• {"endpoint_text":"- Change from baseline in HRQoL as assessed by Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQoL-Lite-CT) domain scores and total score at Week 72","definition_or_measurement_approach":"Change in IWQoL-Lite-CT domain scores and total score from baseline to Week 72."}
• {"endpoint_text":"- Change from baseline at Week 72 in non-HDL cholesterol","definition_or_measurement_approach":"Change in non-HDL cholesterol from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline at Week 72 in VLDL cholesterol","definition_or_measurement_approach":"Change in VLDL cholesterol from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline at Week 72 in total cholesterol","definition_or_measurement_approach":"Change in total cholesterol from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline at Week 72 in free fatty acids","definition_or_measurement_approach":"Change in free fatty acids from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Change from baseline at Week 72 in diastolic blood pressure","definition_or_measurement_approach":"Change in diastolic blood pressure from baseline to Week 72 measured by vital signs."}
• {"endpoint_text":"- Change from baseline at Week 72 in high-sensitivity C-reactive protein (hsCRP)","definition_or_measurement_approach":"Change in hsCRP from baseline to Week 72 measured by laboratory tests."}
• {"endpoint_text":"- Achieve ≥30% body weight loss at Week 72 (Yes/No)","definition_or_measurement_approach":"Proportion of participants achieving ≥30% weight loss from baseline at Week 72 (Yes/No)."}
• {"endpoint_text":"- Change from baseline in BMI at Week 72","definition_or_measurement_approach":"Change in BMI from baseline to Week 72."}
• {"endpoint_text":"- Percent change from baseline in weight by obesity class, at Week 72","definition_or_measurement_approach":"Percent change in weight from baseline to Week 72 stratified by obesity class."}
• {"endpoint_text":"- Time to achieve ≥5%, ≥10%, ≥15%, ≥20%, ≥25% and 30% weight loss from baseline through Week 72 (weeks)","definition_or_measurement_approach":"Time (weeks) from baseline to achievement of specified percent weight loss thresholds through Week 72."}
• {"endpoint_text":"- Change from baseline in total lean tissue volume (liter and %) at Week 72","definition_or_measurement_approach":"Change in total lean tissue volume (liters and percent) from baseline to Week 72 (MRI substudy measures where applicable)."}
• {"endpoint_text":"- Change from baseline in total adipose tissue volume (liter and %) at Week 72","definition_or_measurement_approach":"Change in total adipose tissue volume (liters and percent) from baseline to Week 72 (MRI substudy measures where applicable)."}
• {"endpoint_text":"- Incidence and severity of adverse events (AEs) (including SAEs, AESIs and AEs leading to study drug discontinuation), with severity determined according to mild/moderate/severe criteria","definition_or_measurement_approach":"Incidence and investigator-assessed severity (mild/moderate/severe) of AEs, SAEs, AESIs and AEs leading to discontinuation recorded through Week 72."}
• {"endpoint_text":"- Change from baseline in selected safety laboratory values, vital signs, and ECGs through Week 72","definition_or_measurement_approach":"Change in selected safety laboratory parameters, vital signs and ECG findings from baseline through Week 72."}
• {"endpoint_text":"- Changes from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire-9 (PHQ-9) through Week 72","definition_or_measurement_approach":"Change in C-SSRS and PHQ-9 scores from baseline through Week 72."}

Methods

• Study website (country-specific versions) - online information for potential participants
• Online advertisements / digital assets (Assets Online Adds) - digital recruitment channels
• Study brochure (K2_Recruitment material_Study brochure) - patient-facing printed/digital brochure (available in multiple languages)
• Study flyer (K2_Recruitment material_Study flyer) - patient-facing flyer materials
• Study postcard / CVRM postcard (K2_Recruitment material_Study postcard) - brief mail/print recruitment postcards
• Study poster (K2_Recruitment material_Study Poster) - site-based poster materials
• Pre-Screening Questionnaire (K2_Recruitment material_Pre Screening Questionaire) - online or paper pre-screening tool for potential participants
• Patient letter / Patient participation letter (K2_Recruitment Material_Patient Letter) - direct mail or clinician-delivered invitation
• Patient card / thank you / participant materials (L2_other subject information material, Patient Participation Card) - site distribution
• Multilingual recruitment materials: documents available in English, French, Dutch, Spanish, Czech, Hungarian, Polish, Italian (country-labeled recruitment documents present).

Belgium

Earliest CTIS Part Ii Submission Date

10-04-2026

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

27

Number Of Sites

5

Number Of Participants

58

Czechia

Earliest CTIS Part Ii Submission Date

29-01-2026

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

98

Number Of Sites

7

Number Of Participants

91

France

Earliest CTIS Part Ii Submission Date

24-02-2026

Latest Decision Or Authorization Date

12-05-2026

Processing Time Days

77

Number Of Sites

9

Number Of Participants

84

Germany

Earliest CTIS Part Ii Submission Date

23-04-2026

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

14

Number Of Sites

12

Number Of Participants

100

Hungary

Earliest CTIS Part Ii Submission Date

20-04-2026

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

21

Number Of Sites

7

Number Of Participants

79

Italy

Earliest CTIS Part Ii Submission Date

29-01-2026

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

98

Number Of Sites

9

Number Of Participants

88

Spain

Earliest CTIS Part Ii Submission Date

20-04-2026

Latest Decision Or Authorization Date

13-05-2026

Processing Time Days

23

Number Of Sites

11

Number Of Participants

105

Netherlands

Earliest CTIS Part Ii Submission Date

09-04-2026

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

29

Number Of Sites

5

Number Of Participants

51

Poland

Earliest CTIS Part Ii Submission Date

10-04-2026

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

28

Number Of Sites

10

Number Of Participants

98

Primary sponsor

Full Name

F. Hoffmann-La Roche AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Axon Communications Inc.

Responsibilities

Patient Material- Recruitment/Retention

Name

Pharmaceutical Research Associates Group B.V.

Responsibilities

Bioanalytical Lab ADA

Name

Bioclinica Inc.

Responsibilities

Central Imaging Provider - MRI Central imaging, eCOA/ePRO provider, clinical outcome assessments and supplies

Name

Greenphire LLC

Responsibilities

Patient expense reimbursement

Name

Q2q Communications Limited

Responsibilities

Investigator Meeting organisation

Name

Labcorp Central Laboratory Services SARL

Responsibilities

Central laboratory analyses, sample handling and storage

Name

Pra International

Responsibilities

Bioanalytical Lab PK

Name

4g Clinical LLC

Responsibilities

IxRS Provider, patient enrolment and IMP assignment

Third parties

• {"country":"Canada","full_name":"Axon Communications Inc.","duties_or_roles":"Patient Material- Recruitment/Retention","organisation_type":"Health care"}
• {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"Bioanalytical Lab ADA","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central Imaging Provider - MRI Cental imaging, Clinical Outcome Assessment (eCOA, ePRO) Provider - Clinical outcome assessements PROs / PHQ9 / C-SSRS and eDiary Blood Glucose Monitors and supplies","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient expense reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q2q Communications Limited","duties_or_roles":"Investigator Meeting-IM","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Analysis of patient blood samples taken throughout the study. Study material supplies, sample shipment and storage.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pra International","duties_or_roles":"Bioanalytical Lab PK","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"IxRS Provider, Patient enrollment and IMP assignment","organisation_type":"Non-Pharmaceutical company"}