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Also known as AMG 133, MariTide, AMG 133 (frozen liquid), AMG 133 (liquid)
Maridebart cafraglutide · 29 trials · 16 indications
Heart Failure events include: hospitalization for HF or urgent HF visits.
Change from baseline in QTcF for maridebart cafraglutide will be the dependent variable for calculation of model-derived placebo-corrected, change from baseline in QTcF after maridebart cafraglutide dosing.
A TEAE was defined as any adverse event (AE) which started on or after the first dose of AMG 133. Clinically significant changes in laboratory safety tests, vital signs and 12-lead electrocardiograms (ECGs) were included as AEs.
| Arm | Type | Description |
|---|---|---|
| Maridebart cafraglutide | EXPERIMENTAL | Participants will receive maridebart cafraglutide administered subcutaneously (SC) once every 4 weeks (Q4W) in a dose-escalation manner. |
| Semaglutide | ACTIVE_COMPARATOR | Participants will receive semaglutide administered SC once weekly (QW) in a dose-escalation manner. |
| Maridebart Cafraglutide Low Dose Q4W | EXPERIMENTAL | Participants who received low dose of maridebart cafraglutide in the parent trial (20210184 \[NCT06858878\]) will continue to receive low dose of maridebart cafraglutide subcutaneously (SC) once in 4 weeks (Q4W). |
| Maridebart Cafraglutide Medium Dose Q4W | EXPERIMENTAL | Participants who received medium dose of maridebart cafraglutide in the parent trial will be re-randomized in this trial to receive medium dose of maridebart cafraglutide SC Q4W. |
| Maridebart Cafraglutide Medium dose Q8W | EXPERIMENTAL | Participants who received medium dose of maridebart cafraglutide in the parent trial will be re-randomized in this trial to receive medium dose of maridebart cafraglutide SC once in 8 weeks (Q8W). |
| Placebo Q4W (Received Medium Dose Maridebart Cafraglutide in Parent Trial) | PLACEBO_COMPARATOR | Participants who received medium dose of maridebart cafraglutide in the parent trial will be re-randomized in this trial to receive placebo SC Q4W. |
| Maridebart Cafraglutide High Dose Q4W | EXPERIMENTAL | Participants who received high dose of maridebart cafraglutide in the parent trial will be re-randomized in this trial to receive high dose of maridebart cafraglutide SC Q4W. |
| Maridebart Cafraglutide High Dose Q8W | EXPERIMENTAL | Participants who received high dose of maridebart cafraglutide in the parent trial will be re-randomized in this trial to receive high dose of maridebart cafraglutide SC Q8W. |
| Placebo Q4W (Received High Dose Maridebart Cafraglutide in Parent Trial) | PLACEBO_COMPARATOR | Participants who received high dose of maridebart cafraglutide in the parent trial will be re-randomized in this trial to receive placebo SC Q4W. |
| Maridebart Cafraglutide High Dose Q4W (Received Placebo in the Parent Trial) | EXPERIMENTAL | Participants who received placebo in the parent trial will receive high dose of maridebart cafraglutide SC Q4W. Prior to initiating the assigned high dose, participants will undergo a dose-escalation phase gradually increasing doses. |
| Maridebart Cafraglutide Low Dose Q4W(Received Very Low Dose Maridebart Cafraglutide in Parent Trial) | EXPERIMENTAL | Participants who permanently de-escalated to very low dose of maridebart cafraglutide in the parent trial will receive low dose of maridebart cafraglutide SC Q4W. |
| Maridebart Cafraglutide High Dose Q12W | EXPERIMENTAL | Participants who received high dose of maridebart cafraglutide in the parent trial will be re-randomized in this trial to receive high dose of maridebart cafraglutide SC once in 12 weeks (Q12W). |
| MariTide Arm 1 | EXPERIMENTAL | Participants will receive maridebart cafraglutide dosing schedule 1 during the treatment period. |
| MariTide Arm 2 | EXPERIMENTAL | Participants will receive maridebart cafraglutide dosing schedule 2 during the treatment period. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo SC. |
| Maridebart Cafraglutide High Dose | EXPERIMENTAL | Participants will receive maridebart cafraglutide high dose subcutaneously (SC) for 72 weeks. |
| Maridebart Cafraglutide Medium Dose | EXPERIMENTAL | Participants will receive maridebart cafraglutide medium dose SC for 72 weeks. |
| Maridebart Cafraglutide Low Dose | EXPERIMENTAL | Participants will receive maridebart cafraglutide low dose SC for 72 weeks. |
| Cohort A: Maridebart Cafraglutide | EXPERIMENTAL | Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts. |
| Cohort A: Placebo | PLACEBO_COMPARATOR | Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts . Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts. |
| Cohort B: Maridebart Cafraglutide | EXPERIMENTAL | Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts. |
| Cohort B: Placebo | PLACEBO_COMPARATOR | Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts. |
| Maridebart Cafraglutide (Test) | EXPERIMENTAL | Participants will receive maridebart cafraglutide (test formulation) via subcutaneous (SC) injection. |
| Maridebart Cafraglutide (Reference) | ACTIVE_COMPARATOR | Participants will receive maridebart cafraglutide (reference formulation) via SC injection. |
| COC + Maridebart Cafraglutide | EXPERIMENTAL | Participants will receive COC orally and maridebart cafraglutide subcutaneously (SC). |
| Maridebart Cafraglutide SC Presentation 1 | EXPERIMENTAL | Participants will receive a single dose of maridebart cafraglutide administered using SC presentation 1. |
| Maridebart Cafraglutide SC Presentation 2 | ACTIVE_COMPARATOR | Participants will receive a single dose of maridebart cafraglutide administered using SC presentation 2. |
| Group 1 | EXPERIMENTAL | In treatment period 1, participants will receive placebo for moxifloxacin. In treatment period 2, participants will receive maridebart cafraglutide. In treatment period 3, participants will receive placebo for moxifloxacin. |
| Group 2A | EXPERIMENTAL | In treatment period 1, participants will receive moxifloxacin. In treatment period 2, participants will receive placebo for maridebart cafraglutide. In treatment period 3, participants will receive placebo for moxifloxacin. |
| Group 2B | EXPERIMENTAL | In treatment period 1, participants will receive placebo for moxifloxacin. In treatment period 2, participants will receive placebo for maridebart cafraglutide. In treatment period 3, participants will receive moxifloxacin. |
| AMG 133 | EXPERIMENTAL | Participants will receive AMG 133 subcutaneously (SC) and acetaminophen orally. |
| Group 1, AMG 133: Normal Hepatic Function (No Impairment) | EXPERIMENTAL | Participants with normal hepatic function will receive a single dose of AMG 133 SC on Day 1. |
| Group 2, AMG-133: Child-Pugh A (Mild Hepatic Impairment) | EXPERIMENTAL | Participants with mild hepatic impairment will receive a single dose of AMG 133 SC on Day 1. |
| Group 3, AMG-133: Child-Pugh B (Moderate Hepatic Impairment) | EXPERIMENTAL | Participants with moderate hepatic impairment will receive a single dose of AMG 133 SC on Day 1. |
| Group 4, AMG-133: Child-Pugh C (Severe Hepatic Impairment) | EXPERIMENTAL | Participants with severe hepatic impairment will receive a single dose of AMG 133 SC on Day 1. |
| Group 1: Normal renal function | EXPERIMENTAL | Participants with an estimated glomerular filtration rate (eGFR) of ≥ 90 mL/min will receive a single dose of AMG 133 as a SC injection. |
| Group 2: Mild renal impairment | EXPERIMENTAL | Participants with an eGFR of 60 to \< 90 mL/min will receive a single dose of AMG 133 as a SC injection. |
| Group 3: Moderate renal impairment | EXPERIMENTAL | Participants with an eGFR of 30 to \< 60 mL/min will receive a single dose of AMG 133 as a SC injection. |
| Group 4: Severe renal impairment and kidney failure not receiving hemodialysis | EXPERIMENTAL | Participants with an eGFR of \< 30 mL/min will receive a single dose of AMG 133 as a SC injection. |
| Group 5: Kidney failure receiving hemodialysis | EXPERIMENTAL | Participants with an eGFR of \< 15 mL/min will receive a single dose of AMG 133 as a SC injection. |
| Low Dose AMG 133 without Ondansetron | EXPERIMENTAL | Participants will receive a single subcutaneous (SC) low dose of 70 mg AMG 133. |
| High Dose AMG 133 without Ondansetron | EXPERIMENTAL | Participants will receive a single SC high dose of 350 mg AMG 133. |
| Low Dose AMG 133 with Ondansetron | EXPERIMENTAL | Participants will receive a single SC low dose of 70 mg AMG 133 and ondansetron 8 mg orally disintegrating tablet (ODT) every 8 hours for 72 hours. |
| High Dose AMG 133 with Ondansetron | EXPERIMENTAL | Participants will receive a single SC high dose of 350 mg AMG 133 and ondansetron 8mg ODT every 8 hours for 72 hours. |
| Group 1 (reference): AMG 133 Concentration A (frozen liquid) | EXPERIMENTAL | Participants will receive a single dose of AMG 133 as a SC injection. |
| Group 2 (test): AMG 133 Concentration B (liquid) | EXPERIMENTAL | Participants will receive a single dose of AMG 133 as a SC injection. |
| Group 3 (test): AMG 133 Concentration C (liquid) | EXPERIMENTAL | Participants will receive a single dose of AMG 133 as a SC injection. |
| AMG 133 Dose A | EXPERIMENTAL | Participants will receive AMG 133 Dose A SC, followed by subsequent doses of Dose C and Dose D. |
| AMG 133 Dose B | EXPERIMENTAL | Participants will receive AMG 133 Dose B SC, followed by subsequent doses of Dose C and Dose D. |
| AMG 133 Dose C | EXPERIMENTAL | Participants will receive AMG 133 Dose C SC, followed by subsequent doses of Dose C and Dose D. |
| Group 1: Maridebart Cafraglutide Dose 1 | EXPERIMENTAL | Participants will receive a single SC lower dose of Maridebart Cafraglutide. |
| Group 2: Maridebart Cafraglutide Dose 2 | EXPERIMENTAL | Participants will receive a single SC higher dose of Maridebart Cafraglutide. |
| Part A: maridebart cafraglutide | EXPERIMENTAL | Up to 7 single ascending dose cohorts (cohorts 1 to 6 and cohort 11). |
| Part A: Placebo | PLACEBO_COMPARATOR | Up to 7 single ascending dose cohorts (cohorts 1 to 6 and cohort 11). |
| Part B: maridebart cafraglutide | EXPERIMENTAL | Up to 4 multiple ascending dose cohorts (cohorts 7 to 10). |
| Part B: Placebo | PLACEBO_COMPARATOR | Up to 4 multiple ascending dose cohorts (cohorts 7 to 10). |
| Part C: maridebart cafraglutide | EXPERIMENTAL | Up to 2 open-label, multiple ascending dose cohorts (cohorts 12 to 13) treated with doses previously studied in Part A and Part B. |
| Name | Type | Description |
|---|---|---|
| Maridebart cafraglutide | DRUG | Administered subcutaneously. |
| Semaglutide | DRUG | Administered subcutaneously. |
| Autoinjector | DEVICE | The AI will be used by participants to self-administer SC doses of maridebart cafraglutide. |
| Placebo | DRUG | Administered subcutaneously. |
| COC | DRUG | Administered orally. |
| Moxifloxacin | DRUG | Participants will receive moxifloxacin orally. |
| Placebo for Maridebart Cafraglutide | DRUG | Participants will receive placebo for maridebart cafraglutide SC. |
| Placebo for Moxifloxacin | DRUG | Participants will receive placebo for moxifloxacin orally. |
| AMG 133 | DRUG | AMG 133 will be administered SC. |
| Acetaminophen | DRUG | Acetaminophen will be administered orally. |
| Ondansetron | DRUG | Ondansetron will be administered via ODT. |
| AMG 133 (frozen liquid) | DRUG | AMG 133 will be administered as a SC injection. |
| AMG 133 (liquid) | DRUG | AMG 133 will be administered as a SC injection. |
Inclusion Criteria: * HbA1c of ≥ 7.5% (58.0 millimoles per mole (mmol/mol)) and ≤ 10.5% (91.0 mmol/mol) at screening. * Treatment of Type 2 diabetes (T2D) with metformin (≥ 1500 milligrams per day (mg/day), or maximum tolerated dose as per investigator judgment) with or without an sodium-glucose co...
Maridebart cafraglutide is an investigational small molecule developed by Amgen Inc. (ticker AMGN) for obesity, overweight, atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and obstructive sleep apnea. It is in Phase 3 clinical development and is not yet approved.
Maridebart cafraglutide targets GLP-1. It is a small molecule designed to act on this target, and Amgen is studying it across obesity, overweight, and related cardiovascular and metabolic conditions in a Phase 3 program that includes placebo-controlled, randomized, double-blind trials.
Maridebart cafraglutide is developed by Amgen Inc., which trades under the ticker AMGN. Amgen is running the clinical program, which includes eight trials in total, with five currently active and three completed, enrolling about 12,800 participants across the studies.
Maridebart cafraglutide is in Phase 3 clinical development. It is investigational and has not been approved by the FDA. The program includes Phase 3 trials in obesity, overweight, and type 2 diabetes, plus a Phase 1 study comparing two drug products after a single subcutaneous dose.
Maridebart cafraglutide trials include NCT07684235, a Phase 3 extension study in obesity and overweight that is recruiting, and NCT07871409, a Phase 3 autoinjector self-administration study in obesity or overweight. Other studies include NCT07866066 versus semaglutide in type 2 diabetes and NCT07832799, a Phase 1 comparison of two drug products.
Maridebart cafraglutide is being studied for obesity and overweight, including a Phase 3 extension trial and a Phase 3 home self-administration study with an autoinjector. It is also in development for atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and obstructive sleep apnea, but it remains investigational.