Efficacy and Safety of Apitegromab for the Treatment of Adults Who Are Overweight or Obese (EMBRAZE)

A Phase 2 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Apitegromab in Overweight and Obese Adult Subjects

A phase 2 study to evaluate the effects of apitegromab as an adjunctive therapy to GLP-1 receptor agonist therapy in subjects with overweight or obesity

Study Overview

• Status: Completed
• Conditions: Overweight and Obesity
• Intervention / Treatment: Drug: Apitegromab; Drug: Tirzepatide; Drug: Placebo

Detailed Description

This phase 2 randomized, double-blind, placebo-controlled, multicenter study assessed the safety, efficacy, and pharmacokinetics (PK) of apitegromab when used as an adjunctive therapy to GLP-1 receptor agonist therapy in subjects with overweight and obesity and without diabetes. Each subject received tirzepatide throughout the treatment period. In addition, all subjects were randomized 1:1 to receive either apitegromab or placebo during the treatment period.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • ProSciento CRU
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth Translational Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials, LLC d/b/a Flourish Research
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research GI, LLC
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Alliance for Multispecialty Research, LLC
  • Texas
    • Bellaire, Texas, United States, 77401
      • Apex Mobile Clinical Research
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC dba Flourish Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Able to comprehend the informed consent process and provide written informed consent prior to study enrollment and the conduct of any study-related assessments to study enrollment and the conduct of any study-related assessments
• Male or female, age ≥ 18 and ≤ 65 years at the time of informed consent
• Stable body weight (±5 kg) within 90 days of Screening

• At Screening, a BMI of:

  1. ≥30.0 kg/m2 to ≤45.0 kg/m2 or
  2. ≥27.0 kg/m2 to <30.0 kg/m2 with the presence of 1 or more weight-related comorbid condition(s). Note: See exclusion criteria for specific organ class disease parameters

Exclusion Criteria:

• History of or active cardiovascular, neurovascular, peripheral vascular, pulmonary, hepatic, pancreatic, neuromuscular, and/or psychiatric disease
• Active malignancy, other than local subcutaneous squamous cell and basal cell carcinomas
• History of immunosuppressive, chemotherapeutic, or radiation treatment within 12 months prior to Screening
• History of Type 1 diabetes or active Type 2 diabetes (T2D). If there was a history of T2D and it resolved, then the resolution must have occurred >12 months prior to Screening. Prediabetes managed with nonpharmacologic approaches (exercise and diet) is not an exclusion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Apitegromab + incretin mimetic	Drug: Apitegromab; Apitegromab (SRK-015) is a fully human anti-proMyostatin monoclonal antibody (mAb) that specifically binds to human pro/latent myostatin, inhibiting myostatin activation. Apitegromab was administered every 4 weeks by intravenous (IV) infusion.; Other Names: SRK-015; Drug: Tirzepatide; Glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide was administered every week by subcutaneous injection.; Other Names: ZEPBOUND
Placebo Comparator: Cohort 2; Placebo + incretin mimetic	Drug: Tirzepatide; Glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide was administered every week by subcutaneous injection.; Other Names: ZEPBOUND; Drug: Placebo; Same appearance and composition as apitegromab drug product but does not contain the active ingredient. Placebo was administered every 4 weeks by intravenous (IV) infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in total Lean Body Mass (kg) at 24 weeks	Dual-energy X-ray absorptiometry was used to evaluate body composition	Baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	Incidence and severity of TEAEs and SAEs	Baseline up to 40 weeks
Presence of anti-drug antibodies (ADA) against apitegromab over time	Measured in serum blood samples	Baseline up to 40 weeks
Change from Baseline in body weight	Total body weight was assessed via a calibrated scale	Baseline and 24 weeks
Change from Baseline in percent lean body mass (%)	Dual-energy X-ray absorptiometry was used to evaluate body composition	Baseline and 24 weeks
Change from Baseline in fat body mass (kg and %)	Dual-energy X-ray absorptiometry was used to evaluate body composition	Baseline and 24 weeks
Change from Baseline in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and trunk fat body mass (kg and %)	Dual-energy X-ray absorptiometry was used to evaluate body composition	Baseline and 24 weeks
Percent (%) of weight loss from baseline due to fat body mass loss	Dual-energy X-ray absorptiometry was used to evaluate body composition	Baseline and 24 weeks
Percent (%) of weight loss from baseline due to lean body mass loss	Dual-energy X-ray absorptiometry was used to evaluate body composition	Baseline and 24 weeks
Concentration of apitegromab in circulation over time	Blood samples were assessed for circulating concentration of apitegromab	Baseline up to 40 weeks
Concentration of latent myostatin in circulation over time	Blood samples were assessed for circulating concentration of latent myostatin	Baseline up to 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in HbA1c	Blood samples were assessed for HbA1c (glycated hemoglobin)	Baseline up to 32 weeks
Change from baseline in fasting serum triglycerides	Blood samples were assessed for fasting serum triglycerides	Baseline up to 32 weeks
Change from baseline in total cholesterol	Blood samples were assessed for total cholesterol	Baseline up to 32 weeks
Change from baseline in low-density lipoprotein cholesterol (LDL-C)	Blood samples were assessed for low-density lipoprotein cholesterol (LDL-C)	Baseline up to 32 weeks

Collaborators and Investigators

• Sponsor: Scholar Rock, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2024
• Primary Completion (Actual): March 4, 2025
• Study Completion (Actual): June 17, 2025

Study Registration Dates

• First Submitted: May 22, 2024
• First Submitted That Met QC Criteria: May 30, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Overweight
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide; apitegromab
• Other Study ID Numbers: SRK-015-006

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No