525/2017 A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Mninistered C1-esterase Inhibitor in the Prevention of Heredtary Ang’oedema - F...
`
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`A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneoust Administered C1 -esterase Inhibitor
`in the Prevention of Hereditary Angioedema
`
`This study has been completed.
`
`Sponsor:
`
`CSL Behring
`
`Information provided by (Responsible Party):
`CSL Behring
`
`CIinlcaITflalsgov Identifier:
`NCT01 91 2456
`
`First received: July 29, 2013
`Last updated: April 25. 2017
`Last verified. November 2015
`History of Changes
`
`Full Text View
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`Tabular Wow
`
`No Study Results Posted
`
`Disclaimer
`
`How to Read a Study Record
`
`D Purpose
`
`The aim of this study is to assess the efficacy of C1-esterase inhibitor in preventing hereditary angioedema attacks when it is administered under
`the skin of subjects with hereditary angioedema. The safety of C1-esterase inhibitor will also be assessed. Each subject will enter a run-in period
`of up to 8—weeks. Subjects who complete the run-in period and who are eligible will then enter the treatment phase which comprises two
`sequential treatment periods. In the treatment phase. subjects will be randomized to one of four arms consisting at treatment with low- or higher-
`volume C1-esterase inhibitor in one treatment period and treatment with Iow- or higher-volume placebo in the other treatment period. The study
`will measure the number of hereditary angioedema attacks that subjects experience while receiving each treatment.
`
`CSL EXHIBIT 1021
`
`Condition
`
`Intervention
`
`Hereditary Angioedema Types I and II
`
`Biological: Low-vohme C1 -esterase inhibitor
`Biological: Higher-volume C1-esterase inhibitor
`Biological: Low-vohme placebo
`Biological: Higher-volume placebo
`
`lnterventional
`Study Type:
`Study Design: Allocation: Randomized
`Intervention Model: Crossover Assignment
`Masking: Participant, Care Provider. Investigator, Outcomes Assessor
`Primary Purpose: Prevention
`
`Official Title:
`
`A Double-blind. Randomized, PIacebo-controled. Cross-over Study to Evaluate the Clinical Efficacy and Safety of Subcutaneous
`Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema
`
`Resource links provided by NLM:
`
`Genetics Home Reference related topics: hereditary angioedema
`
`Drug Information available for: SERPING1 protein, human
`
`Genetic and Rare Diseases Information Center resources: Hereditary Angioedema
`
`U.S. FDA Resources
`
`Further study details as provided by CSL Behring:
`
`Primary Outcome Measures:
`- The time-normalized number of hereditary angioedema attacks [Time Frame: During the treatment phase. up to 32 weeks.]
`
`Secondary Outcome Measures:
`
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`Page 1 of 4
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`CSL EXHIBIT 1021
`CSL v. Shire
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`5/25/2017 A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Heredtary Ang’oedema - F...
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`- Percentage of subjects with a 2 50% reduction in the number of hereditary angioedema attacks [Time Frame; During the treatment phase.
`up to 32 weeks. ]
`
`The percentage of subjects with a 2 50% relative reduction in the time-normalzed number of hereditary angioedema attacks during
`treatment with C1 -esterase inhibitor compared with placebo
`
`Number of uses of rescue medication [Time Frame: During the treatment phase, up to 32 weeks. ]
`
`The time-normalized number of uses of rescue medication during treatment with C1 -esterase inhibitor or placebo
`
`Percentage of subjects with adverse events (AE5). [Time Frame: Vtfithin 24 hours of C1-esterase inhibitor or placebo administration.]
`Percentage of subjects with AEs or other specified safety events. [Time Frame: During the treatment phase, up to 32 weeks,]
`
`The percentage of subjects with unsolicited AEs, serious AEs. or other specified safety events during treatment with C1-esterase inhibitor or
`placebo.
`
`Percentage of subjects experiencing solicited AEs [Time Frame: During the treatment phase, up to 32 weeks. ]
`
`The percentage of subjects experiencing solicited AEs (injection site reactions) during treatment with C1-esterase inhibitor or placebo.
`
`Percentage of investigational product injections resulting in solicited AEs [Time Frame: During the treatment phase, up to 32 weeks.]
`
`The percentage of Injections of C1-esterase inhibitor or placebo that result in solicited AEs (injection site reactions).
`
`httpszl/cliricalt’lals.govlct2/show/NCT01912456
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`- Males or females aged 12 years or older.
`- A clinical diagnosis of hereditary angioedema type I or II.
`- Hereditary angioedema attacks over a consecutive 2-month period that required acute treatment, medical attention, or caused significant
`functional impairment.
`
`90
`Enrollment:
`January 2014
`Study Start Date:
`October 2015
`Study Completion Date:
`Primary Completion Date: October 2015 (Final data colection date for primary outcome measure)
`
`Arms
`
`Experimental: Higher-volume phoebe, then low-volume C1-esterase inhibitor
`A higher-vohme dose of placebo will be administered subcutaneously twice a week for up to 16
`weeks. then a low-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a
`week for up to 16 weeks.
`
`Assigned Interventions
`
`Biological: Low—volume C1-
`9513359 inhibitor Biologicali
`Higher-Volume Placebo
`
`Experimental: Low-volime C1 -esterase inhibitor, then higher-volume placebo
`A low-volume dose of Ct -esterase inhibitor will be administered subcutaneously twice a week for up to
`16 weeks, then a higher-volume dose of placebo wil be administered subcutaneously twice a week far
`up to 16 weeks.
`
`Biological: Low-volume C1-
`9515353 inhibitor BiObgicali
`Higher-Volume PlacebO
`
`Experimental: Low-volume placebo, then higher-volume C1-esterase inhibitor
`A low-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks
`then a higher-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week
`for up to 16 weeks.
`
`Biological: Higher-volume C1-
`9513359 inhibnor Bi°|°9i°a|3 LOW-
`V0lume Placebo
`
`Experimental: Higherwolume C1-esterase inhibitor, then low-volume placebo
`A higher-vohme dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up
`to 16 weeks, then a low-volime dose of placebo will be administered subcutaneoust twice a week for
`up to 16 weeks.
`
`Biological: Higher-volume C1-
`SS‘SI’ESG mhibitor BiObgicali LOW-
`V0lume Placebo
`
`D Eligibility
`
`Ages Eligible for Study:
`Sexes Eligible for Study:
`Accepts Healthy Volunteers:
`
`12 Years and older
`All
`No
`
`(Child, Adult, Senior)
`
`Criteria
`
`Inclusion Criteria:
`
`Run-In Period Inclusion Criteria:
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`5/25/2017 A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema - F...
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`- For subjects who have used oral therapy for prophylaxis against HAE attacks within 3 months of Screening: use of a stable regimen within 3
`months of Screening, with no plans to change.
`
`Eligibility Criteria for Entering Treatment Period 1:
`
`- Laboratory confirmation of type lor type II hereditary angioedema, including C1-esterase inhibitor functional activity less than 50% AND C4
`antigen level below the laboratory reference range.
`No clinically significant abnormalities as assessed using laboratory parameters.
`During participation in the run-in period, subjects must have experienced hereditary angioedema attacks that required acute treatment,
`required medical attention, or caused significant functional impairment.
`Exclusion Criteria:
`
`Run-In Period Exclusion Criteria:
`
`F Contacts and Locations
`
`Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a
`study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general
`information, see Learn About Clinical Studies.
`
`Please refer to this study by its ClinicalTrials.gov identifier: NCT01912456
`
`- History of clinical significant arterial or venous thrombosis, or current history of a clinically significant prothrombotic risk.
`-
`Incurable malignancies at screening.
`- Any clinical condition that will interfere with the evaluation of C1-esterase inhibitor therapy.
`- Clinically significant history of poor response to C1-esterase therapy for the management of hereditary angioedema.
`Receiving therapy prohibited by the protocol, including medications for hereditary angioedema prophylaxis.
`Female subjects who started taking or changed dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e.,
`estrogen/progesterone-containing products) within 3 months prior to the screening visit.
`
`httpszllcli nicaltrials.gov/ct2lshow/NCT01912456
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`il Show 39 Study Locations
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`Sponsors and Collaborators
`
`CSL Behring
`
`Investigators
`
`Study Director: Global Clinical Program Director CSL Behring
`
`F More Information
`
`Publications:
`
`Longhurst H, Cicardi M, Craig T, Bork K, Grattan C, Baker J, Li HH, Reshef A, Bonner J, Bernstein JA, Anderson J, Lumry WR, Farkas H,
`K
`
`Responsible Party:
`ClinicalTrials.gov Identifier:
`Other Study ID Numbers:
`
`CSL Behring
`
`_
`
`fies:
`
`Study First Received:
`Last Updated:
`
`2013-006916-10 ( EudraCT Number)
`July 29, 2013
`April 25, 2017
`
`Keywords provided by CSL Behring:
`Hereditary Angioedema
`
`Additional relevant MeSH terms:
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`Page 3 of 4
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`525/2017 A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneoust Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema - F...
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`Hypersensitivity
`Immune System Diseases
`Complement C1s
`Complement Ct Inhibitor Protein
`Complement Ct lnactivator Proteins
`Immunologic Factors
`Physiological Effects of Drugs
`Complement lnactivating Agents
`Immunosuppressive Agents
`
`ClinicalTrials.gov processed this record on May 24, 2017
`
`Angioedemas, Hereditary
`Angioedema
`Hereditary Angioedema Types I and II
`Vascular Diseases
`Cardiovascular Diseases
`Genetic Diseases, Inborn
`Urticaria
`Skin Diseases, Vascular
`Skin Diseases
`Hypersensitivity. Immediate
`
`https://clinicallrials.gov/ct2/show/NCT01912456
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`Page 4 of 4
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