Blinded Safety & Efficacy Placebo Controlled Study of Icatibant for Angiotensin Converting Enzyme Inhibitor Induced Angioedema

NCT01919801 | Completed Phase 3 Results DMC

• 2 other identifiers: HGT-FIR-0962014-001213-12
• Study Type: interventional
• Target: 118
• Locations: 4 countries
• Sites: 55

Brief Summary

This study is being conducted to compare the safety and efficacy of icatibant with placebo in the treatment for Angiotensin-Converting Enzyme Inhibitor (ACE-I)-Induced Angioedema in Adults.

Conditions

Angiotensin Converting Enzyme Inhibitor Induced Angioedema

Keywords

icatibant; Firazyr; ACE-I

Outcome Measures

Primary Outcomes (4)

• Time to Meeting Discharge Criteria (TMDC)

  TMDC was based on the investigator-assessed angioedema-associated upper airway symptom assessments. It was calculated from the time of study drug administration to the earliest time point at which the symptoms of difficulty breathing and difficulty swallowing were absent and the symptoms of voice change and tongue swelling were mild or absent and all subsequent assessments continued to satisfy these conditions. These symptoms were evaluated by the investigator using a 5-point grading scale (0=absent, 1=mild, 2=moderate, 3=severe, and 4=very severe). TMDC was analysed using Kaplan-Meier estimates.

  Day 0 up to Day 5

• Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.

  From start of study drug administration (Day 0) up to follow-up (Day 5)

• Number of Participants With Treatment Emergent Injection Site Reaction

  Injection site reaction included erythema, swelling, cutaneous pain, burning sensation, itching and warm sensation

  Day 0 to Day 5

• Number of Participants With Clinically Significant Changes in Laboratory Evaluation, Vital Signs, Electrocardiogram (ECG) and Physical Examination

  During laboratory evaluation, serum chemistry and hematology blood tests, and urinalysis were performed. Vital signs parameters included evaluation of pulse rate and systolic and diastolic blood pressure. Standard 12-lead ECGs were performed and ECG recordings were read locally at the study site by a cardiologist. Physical examination was performed with examination of major body systems per routine clinical practice.

  Day 0 to Day 5

Secondary Outcomes (5)

• Time to Onset of Symptom Relief (TOSR)

  Day 0 up to Day 5

• Number of Participants Experienced Airway Intervention Due to ACE-I-induced Angioedema

  Day 0 up to Day 5

• Number of Participants Admitted to Hospital or Intensive Care Unit (ICU)

  Day 0 up to Day 5

• Number of Participants Experienced ACE-I-induced Angioedema Attack Following Study Drug Administration

  Day 0 up to Day 5

• Percentage of Participants With Time to Meeting Discharge Criteria (TMDC) at Specified Time Points

  4, 6, and 8 hours post treatment

Other Outcomes (1)

• Area Under the Plasma Concentration Versus Time Curve (AUC) of Icatibant and Its Metabolites (M1 and M2)

  0.75 and 2 hours post-dose

Study Arms (2)

Icatibant

EXPERIMENTAL

Icatibant at a dose of 30 mg will be administered as a single subcutaneous injection

Drug: Icatibant

Placebo

PLACEBO COMPARATOR

Placebo will be administered as a single subcutaneous injection

Drug: Placebo

Interventions

Icatibant DRUG

Single dose of 30 mg icatibant administered within 12 hours of the onset of an acute attack of ACE-I-induced angioedema

Also known as: Firazyr

Icatibant

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female, 18 years of age or older.
• Patient is currently being treated with an ACE inhibitor.
• Patient presenting with an ACE inhibitor-induced angioedema attack of the head and/or neck region within 12 hours of onset (must be sufficiently less than 12 hours to allow study drug to be given with 12 hours of attack onset).
• Angioedema must be considered at least moderate in severity for at least one of the four angioedema-associated airway symptoms (difficulty breathing, difficulty swallowing, voice changes, tongue swelling).
• Patient must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient.
• Females must have a negative urine pregnancy test prior to administration of the study medication, with the exception of those females who have had a total hysterectomy or bilateral oophorectomy, or who are 2 years post-menopausal.

You may not qualify if:

• Patient has a diagnosis of angioedema of other etiology (eg, hereditary or acquired angioedema, allergic angioedema \[eg, food, insect bite or sting, evident clinical response to antihistamines and/or corticosteroids\], anaphylaxis, trauma, abscess or infection or associated disease, local inflammation, local tumor, post-operative or post-radiogenic edema, salivary gland disorders, other \[non-ACE inhibitor\] drug-induced angioedema).
• Patients with a family history of recurrent angioedema.
• Patients who have had a previous episode(s) of angioedema while not on ACE inhibitor therapy.
• Patients with acute urticaria (itchy, erythematous wheals).
• Patients who have an intervention to support the airway (eg, intubation, tracheotomy, cricothyrotomy) due to the current attack of angioedema.
• Patient has any of the following vascular conditions that, in the judgment of the investigator, would be a contraindication to participation in the study.
• Unstable angina pectoris or acute myocardial ischemia
• Hypertensive urgency or emergency (diastolic blood pressure \[DBP\] \>120 mm Hg or systolic blood pressure \[SBP\] \>180 mm Hg)
• Within 1 month of a stroke or transient ischemic attack
• New York Heart Association (NYHA) heart failure class IV
• Patient has a serious or acute condition or illness that, in the judgment of the investigator, would interfere with evaluating the safety and/or efficacy assessments of the study (eg, a condition or illness requiring hemodialysis).
• Patient is pregnant or breast feeding.
• Patient has participated in another investigational study in the past 30 days.
• Patient is unable to understand the nature, scope, and possible consequences of the protocol, or is unlikely or unable to comply with the protocol assessments, or is unlikely to complete the study for any reason.
• Patients who are not suitable for the study in the opinion of the investigator.

Sponsors & Collaborators

• Shire: lead
• PPD Development, LP: collaborator

Study Sites (55)

University of California San Diego Medical Center

La Jolla, California, 92037, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

UF Health Shands Hospital

Gainesville, Florida, 32610, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Federal Health Care Center

Chicago, Illinois, 60064-3048, United States

Location

Cook County Hospital

Chicago, Illinois, 60612, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

Detroit Receiving Hospital and University Health Center

Detroit, Michigan, 48201, United States

Location

Sinai Grace Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

William Beaumont Hospital

Troy, Michigan, 48085, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University

St Louis, Missouri, 63141, United States

Location

Inspira Health Network

Vineland, New Jersey, 08360, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Kings County Hospital Center

Brooklyn, New York, 11203, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

East Carolina University

Greenville, North Carolina, 27835, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Hospital - East

Gahanna, Ohio, 43230, United States

Location

Summit Health

Chambersburg, Pennsylvania, 17201, United States

Location

Hahnemann University Hospital

Philadelphia, Pennsylvania, 19102, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15143, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of South Carolina School of Medicine

Columbia, South Carolina, 29203, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

John Peter Smith Hospital

Fort Worth, Texas, 76104, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0561, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Hotel Dieu Hospital

Kingston, Ontario, K7L 5G2, Canada

Location

Soroka University Medical Center

Beersheba, 84101, Israel

Location

Bnai Zion Medical Center

Haifa, 31048, Israel

Location

Ziv Medical Center

Safed, 13100, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Brighton and Sussex University Hospitals NHS Trust

Brighton, BN2 5BE, United Kingdom

Location

Royal Devon and Exeter Hospital NHS Trust

Exeter, EX2 5DW, United Kingdom

Location

University Hospital Aintree

Liverpool, L9 7AL, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Queen's Medical Centre

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• Sinert R, Levy P, Bernstein JA, Body R, Sivilotti MLA, Moellman J, Schranz J, Baptista J, Kimura A, Nothaft W; CAMEO study group. Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1402-1409.e3. doi: 10.1016/j.jaip.2017.03.003. Epub 2017 May 25.

  PMID: 28552382 RESULT

MeSH Terms

Interventions

icatibant

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2013
• First Posted: August 9, 2013
• Study Start: December 2, 2013
• Primary Completion: August 22, 2015
• Study Completion: August 22, 2015
• Last Updated: June 8, 2021
• Results First Posted: October 10, 2016

Record last verified: 2021-05

Locations

IL (4); CA (3); GB (5); US (43)