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Review
. 2022 Sep 19;10(9):2330.
doi: 10.3390/biomedicines10092330.

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma

Luigino Calzetta  1 , Marina Aiello  1 , Annalisa Frizzelli  1 , Elena Pistocchini  2 , Beatrice Ludovica Ritondo  2 , Paola Rogliani  2 , Alfredo Chetta  1
Affiliations
Review

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma

Luigino Calzetta et al. Biomedicines. .

Abstract

Inhaled corticosteroids (ICS) remain the mainstay of asthma treatment, along with bronchodilators serving as control agents in combination with ICS or reliever therapy. Although current pharmacological treatments improve symptom control, health status, and the frequency and severity of exacerbations, they do not really change the natural course of asthma, including disease remission. Considering the highly heterogeneous nature of asthma, there is a strong need for innovative medications that selectively target components of the inflammatory cascade. The aim of this review was to systematically assess current investigational agents in Phase I and II randomised controlled trials (RCTs) over the last five years. Sixteen classes of novel therapeutic options were identified from 19 RCTs. Drugs belonging to different classes, such as the anti-interleukin (IL)-4Rα inhibitors, anti-IL-5 monoclonal antibodies (mAbs), anti-IL-17A mAbs, anti-thymic stromal lymphopoietin (TSLP) mAbs, epithelial sodium channel (ENaC) inhibitors, bifunctional M3 receptor muscarinic antagonists/β2-adrenoceptor agonists (MABAs), and anti-Fel d 1 mAbs, were found to be effective in the treatment of asthma, with lung function being the main assessed outcome across the RCTs. Several novel investigational molecules, particularly biologics, seem promising as future disease-modifying agents; nevertheless, further larger studies are required to confirm positive results from Phase I and II RCTs.

Keywords: Phase I; Phase II; RCT; asthma; efficacy; investigational.

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Conflict of interest statement

L.C. reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, nonfinancial support from AstraZeneca, grants from Chiesi Farmaceutici, grants from Almirall, personal fees from ABC Farmaceutici, personal fees from Edmond Pharma, grants and personal fees from Zambon, personal fees from Verona Pharma, personal fees from Ockham Biotech. M.A. has no conflicts of interest to declare. A.F. has no conflicts of interest to declare. E.P. has no conflicts of interest to declare. B.L.R. has no conflicts of interest to declare. P.R. reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, personal fees from AstraZeneca, grants and personal fees from Chiesi Farmaceutici, grants and personal fees from Almirall, grants from Zambon, personal fees from Biofutura, personal fees from GlaxoSmithKline, personal fees from Menarini, and personal fees from Mundipharma. A.C. received grants from Menarini and Astra Zeneca and a personal fee from Chiesi.

Figures

Figure 1
Figure 1
PRISMA 2020 flow diagram for the identification of the RCTs included in the qualitative and quantitative syntheses. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT: randomised controlled trial.
Figure 2
Figure 2
Assessment of the risk of bias via the Cochrane RoB 2 tool displayed by means of a traffic light plot of the risk of bias of the included RCTs (A), and weighted plot for the distribution of the overall risk of bias within each bias domain via the Cochrane RoB 2 tool (B) (n = 18 RCTs). Traffic light plot reports five risk of bias domains: D1, bias arising from the randomisation process; D2, bias due to deviations from intended intervention; D3, bias due to missing outcome data; D4, bias in measurement of the outcome; D5, bias in selection of the reported result. Yellow circle indicates some concerns on the risk of bias, green circle represents low risk of bias, and blue circle indicates no information. NA: not available; RCT: randomised controlled trial; RoB: risk of bias.
See this image and copyright information in PMC

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