CINRYZE for the Treatment of Hereditary Angioedema Attacks in Children Under the Age of 12

Each subject received CINRYZE for treatment of a single acute angioedema attack.

• CINRYZE (Biological), also known as C1 inhibitor [human]

Primary outcomes

• Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom [Within 4 hours following treatment]

Secondary outcomes

• Time to Unequivocal Beginning of Relief of the Defining Attack Symptom [Within 4 hours following treatment]
• Time to Complete Resolution of the Attack [Within 1 week following treatment]
• Change in C1 Inhibitor (C1 INH) Antigen and Functional C1 INH Concentrations [Pre-dose, 2, 4, 8 hours post dose on Day 1; Day 2, 3, 5, 8]: Data was not reported due to change in planned analysis.

Sex: All, ages: 2 Years to 11 Years

Inclusion Criteria:

To be eligible for this protocol, subjects must:

1. Be at least 10 kg of body weight.
2. Have a confirmed diagnosis of HAE.
3. Have an acute HAE attack and be able to initiate treatment within 8 hours after onset of symptoms.

Exclusion Criteria:

To be eligible for this protocol, subjects must not:

1. Have any active infectious illness.
2. Have had a prior HAE attack and/or received any C1 INH product within 7 days prior to dosing with study drug.
3. Have received therapy with antifibrinolytics (e.g., tranexamic acid), androgens (e.g., danazol, oxandrolone, stanozolol, or testosterone), ecallantide (Kalbitor®), or icatibant (Firazyr®) within 7 days prior to dosing with study drug.
4. Have a history of allergic reaction to C1 INH products, including CINRYZE (or any of the components of CINRYZE), or other blood products.
5. Have participated in any other investigational drug evaluation within 30 days prior to dosing with study drug, or have previously received treatment with CINRYZE in this study at any time.

Participant flow

Outcome results

• Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom (Primary), Number, participants: 500 U CINRYZE (10-25 kg Body Weight) 3; 1000 U CINRYZE (>25 kg Body Weight) 3; 1500 U CINRYZE (>25 kg Body Weight) 3
• Time to Unequivocal Beginning of Relief of the Defining Attack Symptom (Secondary), Median, hours: 500 U CINRYZE (10-25 kg Body Weight) 1.25 (0.25 to 1.75); 1000 U CINRYZE (>25 kg Body Weight) 0.25 (0.25 to 0.50); 1500 U CINRYZE (>25 kg Body Weight) 0.50 (0.25 to 2.50)
• Time to Complete Resolution of the Attack (Secondary), Median, hours: 500 U CINRYZE (10-25 kg Body Weight) 13.58 (11.48 to 37.35); 1000 U CINRYZE (>25 kg Body Weight) 10.00 (1.57 to 22.33); 1500 U CINRYZE (>25 kg Body Weight) 29.07 (1.58 to 102.33)
• Change in C1 Inhibitor (C1 INH) Antigen and Functional C1 INH Concentrations (Secondary)

Adverse events

Time frame: Adverse events were collected through 1 week following the dose of study drug.

Other adverse events by term

Limitations and caveats: Change in C1 INH antigen and functional C1 INH concentrations endpoint was not analyzed as no participants agreed to additional and optional blood sampling. As a result, no PK parameters were calculated for this study.

• Results publication: Lumry W, Soteres D, Gower R, Jacobson KW, Li HH, Chen H, Schranz J. Safety and efficacy of C1 esterase inhibitor for acute attacks in children with hereditary angioedema. Pediatr Allergy Immunol. 2015 Nov;26(7):674-80. doi: 10.1111/pai.12444. Epub 2015 Aug 11. PMID 26171584

• Study Director, Study director, Takeda