NCT05933499

Brief Summary

In adults with obesity seeking treatment, weight loss would ideally be composed almost exclusively of fat mass. However, loss of muscle mass and bone are unintentional consequences of weight loss, which may have negative effects on health by lessening improvements in glucose and insulin levels, reducing resting metabolic rate, and increasing the risk of falls and fractures. Data in animals and humans suggest that bimagrumab, an investigational new drug for obesity that inhibits the activin type II receptor (ActRII) inhibitor, may help maximize loss of fat mass while maintaining muscle mass when used in combination with a glucagon-like peptide 1 receptor agonist (GLP-1 RA). The investigators hypothesize that in a randomized, placebo-controlled trial of 63 adults with obesity randomized to tirzepatide (GLP-1/GIP RA) + bimagrumab, tirzepatide alone, or bimagrumab alone, the combination of tirzepatide + bimagrumab will result in improvements in muscle, fat, and bone compared to tirzepatide alone or bimagrumab alone when given in addition to a lifestyle intervention for weight loss over 52 weeks.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
63

participants targeted

Target at P25-P50 for phase_2 obesity

Timeline
35mo left

Started Nov 2025

Typical duration for phase_2 obesity

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress15%
Nov 2025Mar 2029

First Submitted

Initial submission to the registry

June 27, 2023

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 6, 2023

Completed
2.3 years until next milestone

Study Start

First participant enrolled

November 5, 2025

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2028

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2029

Last Updated

March 27, 2026

Status Verified

March 1, 2026

Enrollment Period

3.2 years

First QC Date

June 27, 2023

Last Update Submit

March 25, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Change in number of kilograms of lean mass by dual-energy x-ray absorptiometry

    Change in number of kilograms of lean mass by dual-energy x-ray absorptiometry in tirzepatide + bimagrumab vs. tirzepatide groups

    52 weeks

Study Arms (3)

Tirzepatide + bimagrumab

EXPERIMENTAL
Drug: BimagrumabDrug: TirzepatideDietary Supplement: Calcium/Vitamin DBehavioral: Lifestyle and nutrition counseling

Tirzepatide + placebo

ACTIVE COMPARATOR
Drug: TirzepatideDietary Supplement: Calcium/Vitamin DBehavioral: Lifestyle and nutrition counseling

Bimagrumab + placebo

ACTIVE COMPARATOR
Drug: BimagrumabDietary Supplement: Calcium/Vitamin DBehavioral: Lifestyle and nutrition counseling

Interventions

SQ bimagrumab 300mg qweek

Bimagrumab + placeboTirzepatide + bimagrumab

SQ tirzepatide 15mg qweek

Tirzepatide + bimagrumabTirzepatide + placebo

Lifestyle and nutrition counseling consistent with current guidelines for weight management

Bimagrumab + placeboTirzepatide + bimagrumabTirzepatide + placebo
Calcium/Vitamin DDIETARY_SUPPLEMENT

Elemental calcium 1200 mg + vitamin D3 800 IU PO daily

Bimagrumab + placeboTirzepatide + bimagrumabTirzepatide + placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • BMI ≥30 kg/m2 or ≥27kg/m2 with at least one weight-related medical condition
  • Have a history of at least one self-reported unsuccessful behavioral effort to lose body weight
  • Have an established primary care provider

You may not qualify if:

  • Current or prior history of diabetes mellitus based on self-report, use of diabetes medications, HbA1c ≥6.5%, or fasting glucose ≥126 mg/dL
  • Any single serum transaminase level (i.e., ALT, AST, alk phos) ≥3x the upper limit of normal (ULN)
  • Serum lipase and/or amylase levels ≥2x ULN
  • Serum bilirubin level \>1.6 mg/dL
  • Chronic kidney disease (e.g., estimated glomerular filtration rate (eGFR) \< 45 mL/min)
  • Total WBC \<3000/μL, neutrophils \<1500/μL, hemoglobin \<12 g/dL, or platelet count \<100,000/μL
  • Significant coagulopathy, e.g., PT/INR \>1.5
  • History of familial hypertriglyceridemia or serum fasting triglyceride \>500 mg/dL
  • Uncontrolled thyroid disease, defined as abnormal TSH with abnormal fT4
  • Any chronic active infection (e.g., HIV, hepatitis B or C) or hepatitis C treatment within the previous 6 months
  • Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis) or conditions with hepatotoxic potential (e.g., gallbladder or bile duct disease, acute or chronic pancreatitis, exocrine pancreatic insufficiency)
  • Active clinically significant gastric emptying abnormality or chronic use of a drug(s) that directly affect GI motility
  • History of calcium oxalate kidney stones
  • History of clinically significant arrhythmias, unstable angina, myocardial infarction, stroke, coronary artery bypass graft surgery, percutaneous coronary intervention, heart failure, valve disorders or defect, pulmonary hypertension, chronic hypotension (\<100/50), or chronic uncontrolled hypertension (\>160/100)
  • Tachycardia, defined as heart rate \>100 bpm after 5 minutes resting in a sitting position
  • +26 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Obesity

Interventions

bimagrumabTirzepatideCalciumVitamin D

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide ReceptorsReceptors, G-Protein-CoupledReceptors, Cell SurfaceMembrane ProteinsProteinsAmino Acids, Peptides, and ProteinsReceptors, Gastrointestinal HormoneReceptors, PeptideMetals, Alkaline EarthElementsInorganic ChemicalsMetalsBlood Coagulation FactorsBiological FactorsSecosteroidsSteroidsFused-Ring CompoundsPolycyclic Compounds

Central Study Contacts

Melanie S Haines, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Eligible participants will be randomized in 1:1:1 ratio to tirzepatide 15mg SQ qweek + bimagrumab 300mg SQ qweek, tirzepatide 15mg SQ week, or bimagrumab 300mg SQ qweek,
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Medicine

Study Record Dates

First Submitted

June 27, 2023

First Posted

July 6, 2023

Study Start

November 5, 2025

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

March 31, 2029

Last Updated

March 27, 2026

Record last verified: 2026-03

Locations