Safety and Efficacy of NA-931 and Tirzepatide in Adults Who Are Overweight or Obese

Official title

A Randomized, Double-Blind, Placebo-Controlled Multi-Center Study of Oral NA-931, Alone or in Addition to Open Label Subcutaneous Tirzepatide , to Investigate the Efficacy and Safety in Overweight or Obese Men and Women

Overview

A phase 2 study to assess the efficacy of NA-931 alone or in addition to Tirzepatide to assess efficacy and safety in overweight or obese men and women

Detailed description

This Phase 2 study investigates if NA-931 in addition to Tirzepatide can demonstrate synergic effects by enhancing efficacy and reducing adverse events including preserve/increase muscle mass in the presence of weight and/or fat mass loss.

Interventions

• Drug NA-931
  NA-931 (oral, daily), a quadruple receptor agonist Tirzepatide (Zepbound) placebo
• Drug Tirzepatide
  Tirzepatide (s.c. weekly) * Glucagon-like peptide-1 (GLP-1) receptor agonist * Other Names: * Mounjaro * Zepbound NA-931 Placebo (oral, daily)
• Drug Tirzepatide
  Tirzepatide (s.c. weekly), a Glucagon-like peptide-1 (GLP-1) receptor agonist • Other Names: * Mounjaro * Zepbound NA-931 Placebo (oral, daily)
• Drug NA-931
  NA-931, an oral, daily • A quadruple receptor agonist
• Drug NA-931
  NA-931 (oral, daily), a quadruple receptor agonist Tirzepatide (s.c. weekly) * Glucagon-like peptide-1 (GLP-1) receptor agonist * Other Names: * Mounjaro * Zepbound
• Drug NA-931
  NA-931 (oral daily), a quadruple receptor agonist Tirzepatide (s.c. weekly) * Glucagon-like peptide-1 (GLP-1) receptor agonist * Other Names: * Mounjaro * Zepbound
• Drug NA-931 150 mg + no Tirzepatide
  NA-931 150 mg + no Tirzepatide
• Drug NA-931
  NA-931 (oral, daily), a quadruple receptor agonist Tirzepatide (s.c. weekly) * Glucagon-like peptide-1 (GLP-1) receptor agonist * Other Names: * Mounjaro * Zepbound
• Drug NA-931
  NA-931 (oral, daily), a quadruple receptor agonist Tirzepatide (s.c. weekly) * Glucagon-like peptide-1 (GLP-1) receptor agonist * Other Names: * Mounjaro * Zepbound

Primary outcome measures

• Change from baseline in body weight at 48 weeks [Time frame: 48 weeks]

Secondary outcome measures (12)

• Change from baseline in waist circumference (cm) at 48 weeks [Time frame: 48 weeks]
• Change from baseline at 48 weeks in total body fat mass in kilograms (kg) [Time frame: 48 weeks]
• Change from baseline at 48 weeks in percent body fat [Time frame: 48 weeks]
• Change from baseline at 48 weeks in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and trunk fat mass by dual-energy x-ray absorptiometry (DXA) [Time frame: 48 weeks]
• Proportion of participants at 48 weeks with change in waist circumference ≥ 5 cm [Time frame: 48 weeks]
• Proportion of participants at 48 weeks with change in Body weight ≥ 5%, ≥ 10% and ≥15% [Time frame: 48 weeks]
• Proportion of participants at 48 weeks with change in Fat mass ≥ 5% ≥ 10% ≥ 15% by Dual energy X-ray absorptiometry (DXA) [Time frame: 48 weeks]
• Proportion of participants at 48 weeks with change in Fat mass ≥ 10% with <5% decrease (or and increase) in lean mass by Dual energy X-ray absorptiometry (DXA) [Time frame: 48 weeks]
• Percentage of weight loss due to fat mass or lean mass at 48 weeks by dual-energy x-ray absorptiometry (DXA) [Time frame: 48 weeks]
• Change from baseline at 48 weeks in fat mass (kg and %) by bioelectrical impedance analysis (BIA) [Time frame: 48 weeks]
• Change from baseline at 48 weeks in lean mass (kg and %) and appendicular lean mass by dual-energy x-ray absorptiometry (DXA) [Time frame: 48 weeks]
• Change from baseline at 48 weeks in lean mass (kg) by bioelectrical impedance analysis (BIA) [Time frame: 48 weeks]

Eligibility criteria

Inclusion criteria

• A written informed consent must be obtained before any study-related assessments are performed.
• Men and women between 18 and 80 years, inclusive; women of child-bearing potential (defined as those who are not post-menopausal or post-surgical sterilization) must meet both of the following criteria:

• Two negative pregnancy tests (at screening and at randomization, prior to dosing)
• Use of intrauterine device, from at least 3 months before the baseline visit through at least 4 months after the last dose of NA-931/placebo oral, and an additional contraceptive (barrier) method from screening through at least 4 months after the last dose of NA-931/placebo oral.
• Body mass index (BMI) ≥ 30 or BMI ≥ 27 with one or more obesity-associated comorbidities (e.g., hypertension, insulin resistance, sleep apnea, or dyslipidemia)
• Stable body weight (± 5 kg) within 90 days of screening, and body weight <150 kg
• Have a history of at least one self-reported unsuccessful behavioral effort to lose body weight
• Able to communicate well with the Investigator, comply with the study requirements and adhere to the diet and activity programs for the study duration

Exclusion criteria

• • History of, or known hypersensitivity to, monoclonal antibody drugs or a contraindication to Tirzepatide (Zepbound® or Mounjaro®)

• Use of other investigational drugs at the time of enrollment or within 30 days or 5 half-lives of enrollment, whichever is longer, or longer if required by local regulations
• Treatment with any medication for the indication of obesity within the past 30 days before screening
• Diagnosis of diabetes requiring current use of any antidiabetic drug or HbA1c ≥ 6.5% Note: Metabolic syndrome is not an exclusion, even if managed with an anti-diabetic drug such as metformin or an SGLT2 inhibitor. A diagnosis of prediabetes or impaired glucose tolerance managed exclusively with non-pharmacologic approaches (e.g., diet and exercise) is not an exclusion.
• Any chronic infections likely to interfere with study conduct or interpretation such as hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV). History of hepatitis A or hepatitis C successfully treated is not exclusionary. Active COVID-19 infection.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing, or longer if required by local regulation, or plasma donation (> 250 mL) within 14 days prior to the first dose
• Any disorder, unwillingness, or inability not covered by any of the other exclusion criteria, which in the Investigator's opinion, might jeopardize the participant's safety or compliance with the protocol

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 8 centers

• Biomed Research Unit #90067-102 — Los Angeles
• Biomed Research Unit # 92121-103 — San Diego
• Biomed Research Unit # 94104-101 — San Francisco
• Biomed Research Unit # 33012-104 — Hialeah
• Biomed Research Unit # 32256-105 — Jacksonville
• Biomed Research Unit # 33461-106 — Lake Worth
• Biomed Research Unit # 10021-107 — New York
• Biomed Research Unit # 77479-108 — Sugar Land

Australia · 5 centers

• Biomed Research Unit-NSW-2100-109 — Brookvale
• Biomed Research Unit-NSW-2065-110 — Saint Leonards,
• , Australia, 4101 Biomed Research Unit-NSW-4101-111 — South Brisbane
• Biomed Research Unit-VIC-3124-112 — Camberwell
• , Victoria, Australia, 3084 Biomed Research Unit-VIC-3084-113 — Heidelberg West

New Zealand · 4 centers

• Biomed Research Unit-NZ-2025-115 — Papatoetoe
• Biomed Research Unit-NZ- 6242-117 — Newtown
• Biomed Research Unit-NZ-1010-114 — Auckland
• Hamilton, New Zealand, 3200 Biomed Research Unit-NZ-3200-116 — Hamilton

Identifiers

NCT: NCT06732245 · NA-931-200

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗