Investigating the Efficacy and Safety ICATIBANT For The Treatment of Patients With SARS-CoV-2 (COVID-19) Infection

NCT04978051 | Completed Phase 2

• 1 other identifier: HUB-MdI-ICAT·COVID-201
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

To study the efficacy and safety of icatibant in adult patients admitted to hospitalization units for pneumonia caused by COVID-19, without mechanical ventilation, 10±1 days after starting treatment or discharge from hospital if this occurs before 10 days.

Conditions

COVID-19 Pneumonia

Keywords

icatibant

Outcome Measures

Primary Outcomes (2)

• Efficacy of experimental treatment

  Number of patients reaching grade 2 (inpatient, no longer requiring supplemental oxygen and no longer requiring care or grade 1 (hospital discharge) of the ordinal scale of the clinical state of the patient for 48 hours.

  up to 10 days

• Safety of experimental treatment

  Number of patients without an adverse reaction scoring 3, 4 or 5 according to the Criteria of Adverse Event Terminology (CTC-AE).

  up to 10 days

Secondary Outcomes (18)

• Long-term efficacy

  up to 10 days

• Time to achive a clinical response

  up to 40 days

• Time to achive an afebrile state

  up to 40 days

• time from symptom onset to treatment

  up to day 1

• Responders

  up to 40 days

Study Arms (2)

Standard of Care (SoC)

ACTIVE COMPARATOR

Other: SoC

SoC + Icatibant

EXPERIMENTAL

Drug: Firazyr; Other: SoC

Interventions

Firazyr DRUG

Icatibant 10 MG/ML Prefilled Syringe

SoC + Icatibant

SoC OTHER

The SoC could include respiratory support measures, fluid therapy, antipyretic treatment, postural measures, low-molecular-weight-heparins, corticosteroids, such as dexamethasone, remdesivir and other therapeutic options

SoC + Icatibant; Standard of Care (SoC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult patients (18 years or older), both sexes
• Sars-CoV-2 infection confirmed by PCR less than 4 days before randomization
• hospitalized with a diagnosis of SARS-CoV-2 pneumonia
• radiographic evidence of pulmonary infiltrates
• grade 4 or 5 on the ordinal scale for the evaluation of the patient's clinical condition
• pO2/FiO2 \<380
• men and women of childbearing age who have heterosexual relations must be agreement to use the safe method(s) of contraception
• obtaining the informed consent of the patient or the legal representative.

You may not qualify if:

• imminent death (life expectancy less than 72h)
• known hypersensitivity or known adverse reactions to the study drug, or its metabolites or excipients of the formulation
• invasive mechanical ventilation
• participation in any other clinical trial
• ALT or AST \> 5 x ULN
• creatinine clearance \<50 mL/min using the Cockcroft-Gault formula for participants '18 years old \[Cockcroft 1976\]
• patients with recent acute coronary syndrome (\<1 month)
• patients with a history of stroke
• positive pregnancy test
• pregnant or lactating woman

Sponsors & Collaborators

• Sebastian Videla: lead

Study Sites (1)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Related Publications (16)

• Bova M, Guilarte M, Sala-Cunill A, Borrelli P, Rizzelli GM, Zanichelli A. Treatment of ACEI-related angioedema with icatibant: a case series. Intern Emerg Med. 2015 Apr;10(3):345-50. doi: 10.1007/s11739-015-1205-9. Epub 2015 Feb 10.

  PMID: 25666515 BACKGROUND

• Busse PJ, Christiansen SC. Hereditary Angioedema. N Engl J Med. 2020 Mar 19;382(12):1136-1148. doi: 10.1056/NEJMra1808012. No abstract available.

  PMID: 32187470 BACKGROUND

• Bygum A, Caballero T, Grumach AS, Longhurst HJ, Bouillet L, Aberer W, Zanichelli A, Botha J, Andresen I, Maurer M; IOS Study Group. Elderly versus younger patients with hereditary angioedema type I/II: patient characteristics and safety analysis from the Icatibant Outcome Survey. Clin Transl Allergy. 2019 Jul 19;9:37. doi: 10.1186/s13601-019-0272-9. eCollection 2019.

  PMID: 31360439 BACKGROUND

• Cicardi M, Banerji A, Bracho F, Malbran A, Rosenkranz B, Riedl M, Bork K, Lumry W, Aberer W, Bier H, Bas M, Greve J, Hoffmann TK, Farkas H, Reshef A, Ritchie B, Yang W, Grabbe J, Kivity S, Kreuz W, Levy RJ, Luger T, Obtulowicz K, Schmid-Grendelmeier P, Bull C, Sitkauskiene B, Smith WB, Toubi E, Werner S, Anne S, Bjorkander J, Bouillet L, Cillari E, Hurewitz D, Jacobson KW, Katelaris CH, Maurer M, Merk H, Bernstein JA, Feighery C, Floccard B, Gleich G, Hebert J, Kaatz M, Keith P, Kirkpatrick CH, Langton D, Martin L, Pichler C, Resnick D, Wombolt D, Fernandez Romero DS, Zanichelli A, Arcoleo F, Knolle J, Kravec I, Dong L, Zimmermann J, Rosen K, Fan WT. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):532-41. doi: 10.1056/NEJMoa0906393.

  PMID: 20818888 BACKGROUND

• Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.

  PMID: 1244564 BACKGROUND

• Yang G, Tan Z, Zhou L, Yang M, Peng L, Liu J, Cai J, Yang R, Han J, Huang Y, He S. Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients With COVID-19 and Hypertension: A Single-Center Retrospective Study. Hypertension. 2020 Jul;76(1):51-58. doi: 10.1161/HYPERTENSIONAHA.120.15143. Epub 2020 Apr 29.

  PMID: 32348166 BACKGROUND

• Hess R, Wujak L, Hesse C, Sewald K, Jonigk D, Warnecke G, Fieguth HG, de Maat S, Maas C, Bonella F, Preissner KT, Weiss B, Schaefer L, Kuebler WM, Markart P, Wygrecka M. Coagulation factor XII regulates inflammatory responses in human lungs. Thromb Haemost. 2017 Oct 5;117(10):1896-1907. doi: 10.1160/TH16-12-0904. Epub 2017 Aug 17.

  PMID: 28816340 BACKGROUND

• Leach JK, Spencer K, Mascelli M, McCauley TG. Pharmacokinetics of single and repeat doses of icatibant. Clin Pharmacol Drug Dev. 2015 Mar;4(2):105-11. doi: 10.1002/cpdd.138. Epub 2015 Feb 2.

  PMID: 27128215 BACKGROUND

• Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020 May;39(5):405-407. doi: 10.1016/j.healun.2020.03.012. Epub 2020 Mar 20. No abstract available.

  PMID: 32362390 BACKGROUND

• Van De Veerdonk FL, Netea MG, van Deuren M, van der Meer JWM, de Mast Q, Brüggemann RJ, van der Hoeven H. Kinins and cytokines in COVID-19: a comprehensive pathophysiological approach. 10.20944/preprints202004.0023.v1.

  BACKGROUND

• Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, Fang C, Huang D, Huang LQ, Huang Q, Han Y, Hu B, Hu F, Li BH, Li YR, Liang K, Lin LK, Luo LS, Ma J, Ma LL, Peng ZY, Pan YB, Pan ZY, Ren XQ, Sun HM, Wang Y, Wang YY, Weng H, Wei CJ, Wu DF, Xia J, Xiong Y, Xu HB, Yao XM, Yuan YF, Ye TS, Zhang XC, Zhang YW, Zhang YG, Zhang HM, Zhao Y, Zhao MJ, Zi H, Zeng XT, Wang YY, Wang XH; , for the Zhongnan Hospital of Wuhan University Novel Coronavirus Management and Research Team, Evidence-Based Medicine Chapter of China International Exchange and Promotive Association for Medical and Health Care (CPAM). A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020 Feb 6;7(1):4. doi: 10.1186/s40779-020-0233-6.

  PMID: 32029004 BACKGROUND

• Zanichelli A, Maurer M, Aberer W, Caballero T, Longhurst HJ, Bouillet L, Fabien V, Andresen I; IOS Study Group. Long-term safety of icatibant treatment of patients with angioedema in real-world clinical practice. Allergy. 2017 Jun;72(6):994-998. doi: 10.1111/all.13103. Epub 2017 Mar 13.

  PMID: 27926986 BACKGROUND

• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.

  PMID: 31978945 BACKGROUND

• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

  PMID: 32171076 BACKGROUND

• Malchair P, Giol J, Garcia V, Rodriguez O, Ruibal JC, Zarauza A, Llopis F, Matellan L, Bernal T, Solis B, Otero A, Carnaval T, Jofre H, Jacob J, Solanich X, Antoli A, Rocamora G, Videla S. Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial. Clin Infect Dis. 2023 May 24;76(10):1784-1792. doi: 10.1093/cid/ciac984.

  PMID: 36610464 DERIVED

• Malchair P, Otero A, Giol J, Solanich X, Carnaval T, Fernandez-Nistal A, Sanchez-Gabriel A, Montoto C, Lleonart R, Videla S; ICAT-COVID team. A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID). Trials. 2022 Apr 12;23(1):303. doi: 10.1186/s13063-022-06219-7.

  PMID: 35413921 DERIVED

Related Links

• COVID19, WHO
• Icatibant (Firazyr®). Ficha técnica, Febrero 2019.

MeSH Terms

Interventions

icatibant

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of the Clinical Research Support Unit

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 27, 2021
• Study Start: April 12, 2021
• Primary Completion: November 30, 2021
• Study Completion: March 17, 2022
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

ES (1)