Clinical trial NCT04848480: A Research Study to Compare a New Weekly Insulin, Insulin Icodec, and an Available Daily Insulin, Insulin Degludec, Both in Combination With Mealtime Insulin in People With Type 1 Diabetes (ONWARDS 6)
Official title: Efficacy and Safety of Once Weekly Insulin Icodec Compared to Once Daily Insulin Degludec 100 Units/mL, Both in Combination With Insulin Aspart, in Adults With Type 1 Diabetes. A 26-week, Randomised, Multicentre, Open-label, Active-controlled, Parallel Group, Two Armed, Treat-to-target Trial Investigating the Effect on Glycaemic Control and Safety of Treatment With Once Weekly Insulin Icodec Compared to Once Daily Insulin Degludec, Both in Combination With Insulin Aspart in Adults With Type 1 Diabetes, With a 26-week Extension Investigating Long Term Safety
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-04-19
Enrollment: 582
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study compares insulin icodec (a new insulin) to insulin degludec (an insulin already available on the market) in people with type 1 diabetes.

The study will look at how well insulin icodec taken weekly controls blood sugar compared to insulin degludec taken daily.

Participants will either get insulin icodec that participants will have to inject once a week on the same day of the week, or insulin degludec that participants will have to inject once a day at the same time every day. Which treatment participants get is decided at random. Participants will also get a mealtime insulin.

The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach.

The study will last for about 1 year and 2 months. Participants will have 28 clinic visits and 28 phone calls with the study doctor. At 11 clinic visits participants will have blood samples taken.

At 6 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit.

Participants will be asked to wear a sensor that measures your blood sugar all the time. Participants will be asked to wear it for a total of 57 weeks (around 1 year).

Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.


Eligibility criteria: Inclusion Criteria:

* Male or female aged greater than or equal to 18 years at the time of signing informed consent.
* Diagnosed with type 1 diabetes mellitus greater than or equal to 1 year prior to the day of screening.
* Treated with multiple daily insulin injections (basal and bolus insulin analogue regimes) greater than or equal to 1 year prior to the day of screening.
* HbA1c below10% at screening visit based on analysis from central laboratory.

Exclusion Criteria:

* Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
* Chronic heart failure classified as New York Heart Association (NYHA) Class IV at screening.
* Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Primary outcomes:
measure: Change in Glycosylated Haemoglobin (HbA1c) at Week 26
timeFrame: Baseline (week 0), week 26
Secondary outcomes:
measure: Change in Glycosylated Haemoglobin (HbA1c) at Week 52
timeFrame: Baseline (week 0), week 52
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: Baseline (week 0), week 26
measure: Percentage of Time in Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter [mg/dL]) Using Continuous Glucose Monitoring (CGM) System
timeFrame: From week 22 to week 26
measure: Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction
timeFrame: Baseline (week 0), week 26
measure: Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26
timeFrame: From baseline (week 0) to week 26
measure: Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57
timeFrame: From baseline (week 0) to week 57
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by Blood Glucose [BG] Meter): From Baseline (Week 0) to Week 26
timeFrame: From baseline (week 0) to week 26
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by BG Meter): From Baseline (Week 0) to Week 57
timeFrame: From baseline (week 0) to week 57
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26
timeFrame: From baseline (week 0) to week 26
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57
timeFrame: From baseline (week 0) to week 57
measure: Number of Nocturnal Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26
timeFrame: From baseline (week 0) to week 26
measure: Number of Nocturnal Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57
timeFrame: From baseline (week 0) to week 57
measure: Percentage of Time Spent Less Than (<) 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System
timeFrame: From week 22 to week 26
measure: Percentage of Time Spent Greater Than (>) 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System
timeFrame: From week 22 to week 26
measure: Mean Total Weekly Insulin Dose: From Week 24 to Week 26
timeFrame: From week 24 to week 26
measure: Mean Total Weekly Insulin Dose: From Week 50 to Week 52
timeFrame: From week 50 to week 52
measure: Change in Body Weight
timeFrame: Baseline (week 0), week 26
Other outcomes:
Locations:
city: Concord
country: United States
facility: John Muir Physicians Network Clinical Research Center
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: La Jolla
country: United States
facility: Scripps Whittier Diabetes Inst
state: California
city: La Mesa
country: United States
facility: Diabetes & Endocrine Associates
state: California
city: San Mateo
country: United States
facility: Mills-Peninsula Hlth Services
state: California
city: Denver
country: United States
facility: Creekside Endocrine Associates, PC
state: Colorado
city: Fleming Island
country: United States
facility: Northeast Research Institute
state: Florida
city: Fort Lauderdale
country: United States
facility: Center For Diabetes & Endo Care
state: Florida
city: Port Charlotte
country: United States
facility: Hanson Clinical Research Center
state: Florida
city: Saint Augustine
country: United States
facility: Northeast Research Institute
state: Florida
city: Lawrenceville
country: United States
facility: Physicians Research Assoc. LLC
state: Georgia
city: Roswell
country: United States
facility: Endo Res Solutions Inc
state: Georgia
city: Topeka
country: United States
facility: Cotton-O'Neil Diab & Endo Ctr
state: Kansas
city: Rockville
country: United States
facility: Endo and Metab Consultants
state: Maryland
city: Omaha
country: United States
facility: Methodist Physicians Clin
state: Nebraska
city: Las Vegas
country: United States
facility: Palm Research Center Inc-Vegas
state: Nevada
city: Nashua
country: United States
facility: Southern NH Diabetes and Endo_Nashua
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College - Div of Community Endocrinology
state: New York
city: Wilmington
country: United States
facility: Accellacare
state: North Carolina
city: Greenville
country: United States
facility: Prisma Health-Upstate
state: South Carolina
city: Chattanooga
country: United States
facility: Univ Diab & Endo Consultants
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Med Spec LLP
state: Texas
city: Austin
country: United States
facility: Texas Diab & Endo, P.A.
state: Texas
city: Austin
country: United States
facility: Texas Diab & Endo, P.A.
state: Texas
city: Dallas
country: United States
facility: Velocity Clinical Res-Dallas
state: Texas
city: Dallas
country: United States
facility: North Texas Endocrine Center
state: Texas
city: Houston
country: United States
facility: PlanIt Research, PLLC
state: Texas
city: San Antonio
country: United States
facility: NE Clin Res of San Antonio
state: Texas
city: Renton
country: United States
facility: Rainier Clin Res Ctr Inc
state: Washington
city: Graz
country: Austria
facility: Univ.-Klinik für Innere Medizin
city: Innsbruck
country: Austria
facility: Univ.-Klinik für Innere Medizin I
city: Saint Stefan
country: Austria
facility: Fließer-Görzer [Ordination]
city: Wien
country: Austria
facility: Klinik Landstraße
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Klinik Hietzing
city: Winnipeg
country: Canada
facility: Winnipeg Clinic
state: Manitoba
city: St. Johns
country: Canada
facility: Eastern Health Authority
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Nova Scotia Hlth Halifax
state: Nova Scotia
city: Toronto
country: Canada
facility: Centricity Research LMC
state: Ontario
city: Laval
country: Canada
facility: Ctr de rech Clin de Laval
state: Quebec
city: Berlin
country: Germany
facility: Medizinisches Versorgungszentrum Am Bahnhof Spandau GbR
city: Essen
country: Germany
facility: InnoDiab Forschung GmbH
city: Falkensee
country: Germany
facility: Zentrum für klinische Forschung, Dr. med. Lüdemann
city: Lingen
country: Germany
facility: Diabetologische Gemeinschaftspraxis Dr. Staudenmeyer und Dr. Schiwietz
city: Ludwigshafen
country: Germany
facility: Die Praxis am Ludwigsplatz
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Medizinischen Klinik I am Campus Lübeck
city: Münster
country: Germany
facility: Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
city: Oldenburg I. Holst
country: Germany
facility: RED-Institut für medizinische Studien und Fortbildung GmbH
city: Saint Ingbert-Oberwürzbach
country: Germany
facility: Zentrum für klinische Studien Alexander Segner
city: Ahmedabad
country: India
facility: Diacare diabetes Hormonal Clinic
state: Gujarat
city: Kozhikode
country: India
facility: Calicut Medical College
state: Kerala
city: New Dehli
country: India
facility: All India Institute of Medical Sciences
state: New Delhi
city: Hyderabad
country: India
facility: Care Hospital
city: New Delhi
country: India
facility: Lady Hardinge Medical College
city: Thriruvananthapuram
country: India
facility: Jothydev's Diabetes & Research Center
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia;Ospedale S. Maria della Misericordia
state: Umbria
city: Catanzaro
country: Italy
facility: Policlinico Mater Domini Università di Catanzaro
city: Milano
country: Italy
facility: Osp. San Raffaele Diabetes Research Institute, Dibit 1
city: Roma
country: Italy
facility: Policlinico Umberto I Clinica Medica DH Diabetologia
city: Rome
country: Italy
facility: Policlinico A. Gemelli
city: Koriyama-shi
country: Japan
facility: Seino Internal Medicine Clinic
state: Fukushima, Japan
city: Sapporo-shi, Hokkaido
country: Japan
facility: Manda Memorial Hospital
state: Hokkaido, Japan
city: Kumamoto-shi
country: Japan
facility: Jinnouchi Hospital
state: Kumamoto, Japan
city: Chuo-ku, Tokyo
country: Japan
facility: The Institute of Medical Science, Asahi Life Foundation
city: Kanagawa
country: Japan
facility: H.E.C Science Clinic
city: Sapporo-shi, Hokkaido
country: Japan
facility: Yuri Ono Clinic
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen Apeldoorn
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Moscow
country: Russian Federation
facility: National Medical Research Center of Endocrinology
city: Moscow
country: Russian Federation
facility: Endocrinological Dispensary of Department of healthcare ser.
city: Moscow
country: Russian Federation
facility: Endocrinology Dpt,Post-Graduate Medical Education Faculty
city: Saint Petersburg
country: Russian Federation
facility: SPb SBHI "Snegirev Maternity Hospital No. 6"
city: Saint-Petersburg
country: Russian Federation
facility: City Consultative & Diagnostic Centre #1
city: Saratov
country: Russian Federation
facility: SHI Saratov City Clinical Hospital #9
city: Saratov
country: Russian Federation
facility: Saratov regional clinical hospital
city: St. Petersburg
country: Russian Federation
facility: SPb SBHI City Multifield Hospital #2
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Clinical Consultive-diagnostic Centre
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Málaga
country: Spain
facility: Hospital Clínico Virgen de la Victoria
city: Oviedo
country: Spain
facility: Hospital Univ. Central de Asturias
city: Sevilla
country: Spain
facility: Clínica Nuevas Tecnologías en Diabetes y Endocrinología
city: Adana
country: Turkey
facility: Cukurova Universitesi Tip Fakultesi
city: Aydin
country: Turkey
facility: Adnan Menderes Universitesi Uygulama ve Arastirma Hastanesi
city: Istanbul
country: Turkey
facility: Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi
city: Istanbul
country: Turkey
facility: TC SB Ist.İl Sag.Müd.Prof.Dr.Cemil Tascioglu Sehir Hastanesi
city: Istanbul
country: Turkey
facility: Haydarpasa Numune Egitim Arastirma Hastanesi Endokrinoloji
city: Kayseri
country: Turkey
facility: Erciyes Universitesi Tip Fakultesi
city: Malatya
country: Turkey
facility: İnönü Üniversitesi Turgut Özal Tıp Merkezi
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital_Cambridge
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Stevenage
country: United Kingdom
facility: Lister Hospital
city: Swansea
country: United Kingdom
facility: Joint Clinical Research Facility - Swansea
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (1452)
role: STUDY_DIRECTOR
References:
citation: Philis-Tsimikas A, Bajaj HS, Begtrup K, Cailleteau R, Gowda A, Lingvay I, Mathieu C, Russell-Jones D, Rosenstock J. Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes. Diabetes Obes Metab. 2023 Feb;25(2):331-341. doi: 10.1111/dom.14871. Epub 2022 Oct 14.