A Study of Insulin Efsitora Alfa (LY3209590) as a Weekly Basal Insulin Compared to Insulin Glargine in Adult Participants With Type 2 Diabetes on Multiple Daily Injections (QWINT-4)

A Phase 3, Parallel-Design, Open-Label, Randomized Controlled Study to Evaluate the Efficacy and Safety of LY3209590 as a Weekly Basal Insulin Compared to Insulin Glargine in Adults With Type 2 Diabetes on Multiple Daily Injections

The reason for this study is to evaluate if the once-weekly study drug insulin efsitora alfa (LY3209590) is safe and effective compared with daily insulin glargine in participants with Type 2 diabetes (T2D) that have already been treated with basal insulin and at least 2 injections per day of prandial insulin. The study consists of a 3-week screening/lead-in period, a 26-week treatment period and a 5-week safety follow-up period. The study will last up to 34 weeks.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Type 2 Diabetes Treated With Insulin
• Intervention / Treatment: Drug: Insulin Lispro (U100); Drug: Insulin Glargine (U100); Drug: Insulin Efsitora Alfa

• Study Type: Interventional
• Enrollment (Actual): 730
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: ClinicalTrials.gov@lilly.com

Study Locations

• Argentina
  • Ciudad Autónoma de Buenos Aires, Argentina, C1440AAD
    • CENUDIAB
  • Córdoba, Argentina, 5000
    • Instituto de Investigaciones Clínicas Córdoba
  • Santa Fe, Argentina, 3000
    • Centro de Investigaciones Clinicas del Litoral
  • Buenos Air
    • Ciudad Autonoma de Buenos Aire, Buenos Air, Argentina, C1405BUB
      • Consultorio de Investigación Clínica EMO SRL
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1060ABN
      • CEDIC
    • Ciudad Autónoma de Buenos Aire, Buenos Aires, Argentina, 1056
      • Centro de Investigaciones Metabólicas (CINME)
    • San Nicolas, Buenos Aires, Argentina, 2900
      • Go Centro Medico San Nicolás
  • Ciudad Autónoma De Buenos Aire
    • Caba, Ciudad Autónoma De Buenos Aire, Argentina, 1204
      • Instituto Centenario
    • Ciudad Autonoma de Buenos Aire, Ciudad Autónoma De Buenos Aire, Argentina, C1425AGC
      • Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
  • Ciudad Autónoma De Buenos Aires
    • Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina, C1128AAF
      • Mautalen Salud e Investigación
    • Caba, Ciudad Autónoma De Buenos Aires, Argentina, C1061AAS
      • CIPREC
  • Córdoba
    • Río Cuarto, Córdoba, Argentina, 5800
      • Instituto Médico Río Cuarto
  • La Pampa
    • Santa Rosa, La Pampa, Argentina, 6300
      • Centro de Salud e Investigaciones Médicas
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Instituto Médico Catamarca IMEC
    • Rosario, Santa Fe, Argentina, 2000
      • Instituto de Investigaciones Clinicas Rosario-Sanatorio Delta
  • Tucumán
    • SAN M. DE Tucuman, Tucumán, Argentina, T4000AXL
      • Centro de Investigaciones Médicas Tucuman
• Germany
  • Bad Mergentheim, Germany, 97980
    • Diabetespraxis Mergentheim
  • Hamburg, Germany, 22607
    • Diabeteszentrum Hamburg West
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • ClinPhenomics GmbH & Co KG
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45136
      • InnoDiab Forschung GmbH
    • Münster, Nordrhein-Westfalen, Germany, 48145
      • Institut für Diabetesforschung GmbH Münster
    • Münster, Nordrhein-Westfalen, Germany, 48153
      • Schwerpunktpraxis für Diabetes und Ernährungsmedizin Dr. med. Winfried Keuthage
  • Schleswig-Holstein
    • Oldenburg, Schleswig-Holstein, Germany, 23758
      • RED-Institut GmbH
• India
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education & Research (PGIMER)
  • Karnataka
    • Bangalore, Karnataka, India, 560092
      • Life Care Hospital and Research Centre
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Topiwala National Medical College & B. Y. L. Nair Charitable Hospital
    • Mumbai, Maharashtra, India, 400058
      • BSES MG Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Madras Diabetes Research Foundation
  • Telangana
    • Hyderabad, Telangana, India, 500012
      • Osmania General Hospital
• Italy
  • Ancona, Italy, 60125
    • INRCA Ancona
  • Bologna, Italy, 40138
    • IRCCS - AOU di Bologna
  • Brescia, Italy, 25123
    • Azienda Ospedaliera Spedali Civili di Brescia
  • Catanzaro, Italy, 88100
    • Azienda Ospedaliera Mater Domini
  • Palermo, Italy, 90127
    • Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli
  • Frosinone
    • Ceccano, Frosinone, Italy, 03023
      • Osepdale Civile Fr 5
  • Lazio
    • Roma, Lazio, Italy, 00186
      • "Fatebenefratelli Isola Tiberina - Gemelli Isola"
  • Sardegna
    • Olbia, Sardegna, Italy, 07026
      • Ospedale san Giovanni di Dio-Diabetologia
• Mexico
  • Chihuahua, Mexico, 31217
    • Investigacion En Salud Y Metabolismo Sc
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Unidad de Investigación Clínica y Atención Médica HEPA
    • Guadalajara, Jalisco, Mexico, 44670
      • Private Practice - Dr. Arechavaleta Granell Maria del Rosario
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 66460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
    • San Nicolás de los Garza, Nuevo León, Mexico, 66465
      • Unidad Médica para la Salud Integral
  • Tamaulipas
    • Ciudad Madero, Tamaulipas, Mexico, 89440
      • Centro de Estudios de Investigacion Metabolicos y Cardiovasculares, S.C.
• Puerto Rico
  • Bayamon, Puerto Rico, 00959
    • Centro de Endocrinologia Alcantara Gonzalez
  • Manati, Puerto Rico, 00674
    • Manati Center for Clinical Research
• Spain
  • Granada, Spain, 18016
    • Hospital Universitario San Cecilio
  • Sevilla, Spain, 41003
    • Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)
  • A Coruña [La Coruña]
    • A Coruña, A Coruña [La Coruña], Spain, 15006
      • CHUAC-Complejo Hospitalario Universitario A Coruña
    • Ferrol, A Coruña [La Coruña], Spain, 15405
      • Complejo Hospitalario Universitario de Ferrol (CHUF)- Hospital Naval
  • Andalucía
    • Malaga, Andalucía, Spain, 29010
      • Hospital Universitario Virgen de la Victoria
  • Balears [Baleares]
    • Palma, Balears [Baleares], Spain, 07120
      • Hospital Universitari Son Espases
  • Castilla Y León
    • Valladolid, Castilla Y León, Spain, 47010
      • Hospital Clínico Universitario de Valladolid
  • Catalunya [Cataluña]
    • Barcelona, Catalunya [Cataluña], Spain, 08041
      • Hospital de La Santa Creu i Sant Pau
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
  • Sevilla
    • Seville, Sevilla, Spain, 41950
      • Vithas Hospital Sevilla
  • Valenciana, Comunitat
    • Alzira, Valenciana, Comunitat, Spain, 46600
      • Hospital Universitario de La Ribera
    • Valencia, Valenciana, Comunitat, Spain, 46014
      • Hospital General Universitario de Valencia
• United States
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • CMR of Greater New Haven, LLC
  • Florida
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • Weston, Florida, United States, 33331
      • Encore Medical Research - Weston
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Clinical Trials
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Maryland
    • Baltimore, Maryland, United States, 21239
      • MedStar Good Samaritan Hospital
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • NECCR PrimaCare Research
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center Sunset
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center Tenaya
  • New York
    • Buffalo, New York, United States, 14221
      • Research Foundation of SUNY - University of Buffalo
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington Davis Clinical Research
    • Dublin, Ohio, United States, 43016
      • Aventiv Research
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Multispecialty Group, Inc
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Austin, Texas, United States, 78749
      • Texas Diabetes & Endocrinology, P.A.
    • Austin, Texas, United States, 78731
      • Texas Diabetes & Endocrinology, P.A.
    • Dallas, Texas, United States, 75231
      • North Texas Endocrine Center
    • Houston, Texas, United States, 77043
      • Biopharma Informatic, LLC
    • Plano, Texas, United States, 75093
      • Research Institute of Dallas
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
  • Utah
    • Saint George, Utah, United States, 84790
      • Chrysalis Clinical Research
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a diagnosis of T2D according to the world health organization (WHO) criteria, currently treated with basal insulin and at least 2 injections of prandial insulin per day.
• Are receiving ≥10 units of total basal insulin per day at screening.
• Are receiving ≤2 units/kilogram/day of total daily insulin at screening
• Have an HbA1c value of 7.0% to 10%, inclusive, as determined by the central laboratory at screening

• Have been treated with a stable regimen of one of the following basal insulins used according to local product label with or without noninsulin diabetes therapy for at least 90 days prior to screening

  • once daily U-100 or U-200 insulin degludec
  • once daily U-100 or U-300 insulin glargine
  • once or twice daily U-100 insulin detemir or
  • once or twice daily human insulin Neutral Protamine Hagedorn

• Have been treated with at least twice daily dosing of one of the following insulins used according to local product label for at least 90 days prior to screening. One dose of prandial insulin must occur at the evening meal.

  • Insulin lispro-aabc
  • Insulin lispro (U-100 and U-200)s, IN], U-100 or U200)
  • Insulin aspart (U-100)
  • Insulin glulisine (U-100), or
  • Regular insulin (U-100)

• Acceptable noninsulin diabetes therapies may include 0 to up to 3 of the following with a stable dose for at least 90 days prior to screening

  • dipeptidyl peptidase IV inhibitors
  • sodium-glucose co-transporter-2 inhibitors
  • biguanides (for example, metformin), or
  • glucagon-like peptide-1 receptor agonists Note: All noninsulin diabetes therapies must be used in accordance with the corresponding local product label at the time of screening, and participants should be willing to continue stable dosing throughout the study
  • Have a body mass index ≤45 kilogram/square meter (kg/m²)

Exclusion Criteria:

• Have a diagnosis of type 1 diabetes mellitus or latent autoimmune diabetes, or specific type of diabetes other than T2D (for example, monogenic diabetes, diseases of the exocrine pancreas, drug-induced or chemical-induced diabetes).

• Are currently receiving any of the following insulin therapies anytime in the past 90 days:

  • insulin mixtures
  • insulin human, inhalation powder, or
  • continuous subcutaneous insulin infusion therapy, or
  • regular insulin U-500
• Have a history of greater than 1 episode of ketoacidosis or hyperosmolar state/coma requiring hospitalization in the 6 months prior to screening
• Have had any episodes of severe hypoglycemia, defined as requiring assistance due to neurologically disabling hypoglycemia, within the 6 months prior to screening
• Have hypoglycemia unawareness in the opinion of the investigator
• Anticipate making changes in personal CGM or flash glucose monitoring (FGM) use (for example, initiation, stopping, or changing device) during the study.
• Have had New York Heart Association Class IV heart failure or any of the following cardiovascular conditions in the past 3 months prior to screening: acute myocardial infarction, cerebrovascular accident (stroke), or coronary bypass surgery.
• Have undergone gastric bypass (bariatric) surgery, restrictive bariatric surgery, or sleeve gastrectomy within 1 year prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Insulin Glargine + Insulin Lispro; Participants will be given insulin glargine by SC injection along with insulin lispro	Drug: Insulin Lispro (U100); Administered SC; Other Names: Humalog; Drug: Insulin Glargine (U100); Administered SC; Other Names: Basaglar
Experimental: Insulin Efsitora Alfa + Insulin Lispro; Participants will be given insulin efsitora alfa by subcutaneous (SC) injection along with insulin lispro	Drug: Insulin Lispro (U100); Administered SC; Other Names: Humalog; Drug: Insulin Efsitora Alfa; Administered SC; Other Names: LY3209590 and Basal Insulin-FC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in HbA1c	Change from Baseline in HbA1c of insulin efsitora alfa compared to insulin glargine on glycemic control in adult participants with type 2 diabetes on multiple daily injections.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving HbA1c <7% without Nocturnal Hypoglycemia	Percentage of participants achieving HbA1c <7% without nocturnal hypoglycemia milligram/deciliter (mg/dL) [3.0 millimole/Liter (mmol/L) or severe] during treatment phase up to week 26.	Week 26
Nocturnal Hypoglycemia Event Rate	The event rate of participant-reported clinically significant nocturnal hypoglycemia <54 mg/dL (3.0 mmol/L) or severe) measured during treatment phase up to week 26.	Baseline to Week 26
Change from Baseline in Fasting Glucose	Change from baseline in fasting glucose measured by small monitoring blood glucose (SMBG)	Baseline, Week 26
Time in Glucose Range	Time in glucose range between 70 and 180 mg/dL (3.9 and 10.0 mmol/L), inclusive measured during the continuous glucose monitoring (CGM) session	Week 22 to Week 26
Time in Hypoglycemia Range	Time in hypoglycemia range with glucose <54 mg/dL (3.0 mmol/L), measured by CGM	Week 22 to Week 26
Time in Hyperglycemia Range	Time in hyperglycemia range with glucose >180 mg/dL (10.0 mmol/L), measured by CGM	Week 22 to Week 26
Glucose Variability	Glucose variability measured during the CGM session	Week 22 to Week 26
Basal Insulin Dose		Week 26
Bolus Insulin Dose		Week 26
Total Insulin Dose		Week 26
Basal Insulin Dose to Total Insulin Dose Ratio		Week 26
Hypoglycemia Event Rate	Incidence and rate of composite of level 2 and 3 hypoglycemia event	Baseline to Week 26
Change from Baseline in Body Weight		Baseline, Week 26
Treatment Experience for Diabetes Injection Device at Week 26 - Experience Questionnaire (DID-EQ)	The DID-EQ is a self-administered 10-item questionnaire designed to assess participants' perceptions of diabetes injection delivery systems for T2D. Each item is rated on a four-point Likert scale. Scores are transformed and range from 0 to 100. Higher scores indicate more positive perceptions of injection device characteristics.	Week 26

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) Mon- Fri 9 AM -5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY3209590 as a Weekly Basal Insulin Compared to Insulin Glargine in Adult Participants With Type 2 Diabetes on Multiple Daily Injections (QWINT-4)

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Actual): February 27, 2024
• Study Completion (Actual): February 27, 2024

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro
• Other Study ID Numbers: 18260; I8H-MC-BDCV (Other Identifier: Eli Lilly and Company); 2021-005878-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No