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Clinical Trial
. 2023 Feb;25(2):331-341.
doi: 10.1111/dom.14871. Epub 2022 Oct 14.

Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes

Athena Philis-Tsimikas  1 , Harpreet S Bajaj  2   3 , Kamilla Begtrup  4 , Roman Cailleteau  4 , Amoolya Gowda  4 , Ildiko Lingvay  5   6 , Chantal Mathieu  7 , David Russell-Jones  8   9 , Julio Rosenstock  10
Affiliations
Clinical Trial

Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes

Athena Philis-Tsimikas et al. Diabetes Obes Metab. 2023 Feb.

Abstract

Aim: To describe the phase 3a ONWARDS clinical development programme investigating insulin icodec (icodec), a once-weekly basal insulin, including the design and rationale for each of the ONWARDS 1-6 trials.

Materials and methods: Six randomized controlled trials have been initiated in adults with type 2 diabetes (T2D) (insulin-naive: ONWARDS 1, 3 and 5; previously insulin-treated: ONWARDS 2 and 4) and type 1 diabetes (T1D) (ONWARDS 6). Each trial will investigate icodec use in a unique clinical scenario, with consideration of long-term safety and varied comparator treatments (insulin glargine U100 or U300 or insulin degludec). ONWARDS 5 will incorporate real-world elements and a digital dose titration solution to guide icodec dosing. The primary objective for each of the trials is to compare the change in HbA1c from baseline to week 26 or week 52 between icodec and comparator arms. Secondary objectives include investigating other glycaemic control and safety parameters, such as fasting glucose, time in glycaemic range and hypoglycaemia. Patient-reported outcomes will assess treatment satisfaction.

Conclusions: The ONWARDS 1-6 trials will evaluate the efficacy and safety of once-weekly icodec compared with currently available daily basal insulin analogues in T2D and T1D. These trials will generate comprehensive evidence of icodec use in diverse populations across the spectrum of diabetes progression and treatment experience.

Keywords: basal insulin; phase III study; type 1 diabetes; type 2 diabetes.

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Conflict of interest statement

A.P.‐T. performs research and serves as an advisor on behalf of her employer for Abbott, Dexcom, Lilly, Medtronic, Novo and Sanofi. There are no direct or indirect transfers of funds. H.S.B. reports trial fees paid to his institution by Novo Nordisk during the conduct of ONWARDS 3 and 5; and trial fees paid to his institution by Amgen, AstraZeneca, Boehringer Ingelheim, Ceapro, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals Co. Ltd, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sanofi and Tricida, outside the submitted work. K.B., R.C. and A.G. are employees of Novo Nordisk A/S and may hold stock in Novo Nordisk A/S. I.L. received research funding, advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, GI Dynamics, Eli Lilly, Intarcia, Intercept, Janssen, Merck, Mannkind, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, TARGETPharma, Valeritas and Zealand Pharma. C.M. serves or has served on the advisory panel for Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Imcyse, Insulet, Zealand Pharma, Avotres, Mannkind, Sandoz and Vertex. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for C.M. from Medtronic, Imcyse, Novo Nordisk, Sanofi and ActoBio Therapeutics; C.M. serves or has served on the speakers bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, Astra Zeneca and Novartis. Financial compensation for these activities has been received by KU Leuven. D.R.‐J. has received research funding, speaker or advisory board fees from Eli Lilly, Novo Nordisk, Takeda, Novartis, AstraZeneca, Sanofi, Dexcom and Pfizer. J.R. has served on advisory panels for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia, Novo Nordisk, Oramed, Hanmi, Sanofi and Zealand and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Novartis, Intarcia, Merck, Novo Nordisk, Oramed, Pfizer and Sanofi.

Figures

FIGURE 1
FIGURE 1
Study designs for the ONWARDS trials Following the end‐of‐treatment visit, participants will be transferred to a suitable marketed product at the discretion of the investigator. T1D, type 1 diabetes; T2D, type 2 diabetes
FIGURE 2
FIGURE 2
Confirmatory hypotheses in the ONWARDS 1–6 trials: hierarchicalapproach to adjust for multiplicity. Aspart, insulin aspart; degludec; insulindegludec; glargine, insulin glargine; HbA1c, glycated haemoglobin; icodec, insulin icodec; TIR, time intarget range (3.9–10.0 mmol/L [70–180 mg/dL])
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References

    1. Draznin B, Aroda VR, Bakris G, et al. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes‐2022. Diabetes Care. 2022;45(Suppl 1):S125‐S143. - PubMed
    1. Yen F‐S, Hwu C‐M. Challenges of optimizing insulin therapy for patients with type 2 diabetes mellitus. J Diabetes Investig. 2021;12(9):1523‐1525. - PMC - PubMed
    1. Nyenwe EA, Jerkins TW, Umpierrez GE, Kitabchi AE. Management of type 2 diabetes: evolving strategies for the treatment of patients with type 2 diabetes. Metabolism. 2011;60(1):1‐23. - PMC - PubMed
    1. Peyrot M, Rubin RR, Lauritzen T, et al. Resistance to insulin therapy among patients and providers: results of the cross‐national diabetes attitudes, wishes, and needs (DAWN) study. Diabetes Care. 2005;28(11):2673‐2679. - PubMed
    1. Khunti K, Gomes MB, Pocock S, et al. Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: a systematic review. Diabetes Obes Metab. 2018;20(2):427‐437. - PMC - PubMed

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