525/2017
`
`Subcutaneous CIN RYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks - Full Text \fiew - ClinicalTrials.gov
`
`C[in icalTrials.gov
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`
`Subcutaneous CINRYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks
`
`This study has been completed.
`
`Sponsor:
`Shire
`
`I
`Collaborator:
`Halozyme Therapeutlt?s
`Information provided by (Responslble Party):
`Shire
`
`Clinicifielagov Identifier:
`NCT01 7561 57
`
`First received: June 29, 2012
`Last updated: May 29. 2015
`Last verified: June 2014
`History of Changes
`
`CSL EXHIBIT 103 5
`
`Full Text View
`
`Tabular \fiow
`
`Study Results
`
`Disclaimer
`
`How to Read a Study Record
`
`D Purpose
`
`The primary objectives of the study are to evaluate the safety, tolerability. and efficacy of two doses of CINRYZE with recombinant human
`hyaluronldase (rHuPH20) administered by subcutaneous (SC) injection to prevent angioedema attacks.
`
`Condition
`
`Intervention
`
`Hereditary Angioedema
`
`Biological: CIN RYZE with rHuPHZO
`
`Interventional
`Study Type:
`Study Design: Allocation: Randomized
`Intervention Model: Crossover Assignment
`Masking: Double Bind (Participant, Care Provider. Investigator, Outcomes Assessor)
`Primary Purpose: Prevention
`
`Official Title:
`
`A Phase 2, Randomized, Double-Blind, Multicenter, Dose-Ranging, Crossover Study to Evaluate the Safety and Efficacy of
`Subcutaneous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) With Recombinant Human Hyaluronidase
`(rHuPH20) for the Prevention of Angioedema Attacks in Adolescents and Adults Vifith Hereditary Angioedema
`
`Resource Ilnks provlded by NLM:
`
`Genetics Home Reference related topics: hereditary angioedema
`
`Drug Information available for: Hyaluronidase SERPING1 protein. human
`
`Genetic and Rare Diseases Information Center resources: Hereditary Angioedema
`U.S. FDA Resources
`
`Further study details as provided by Shire:
`
`Primary Outcome Measures:
`
`- Normalized Number of Angioedema Attacks During the Treatment Period [Time Frame: From \fisit 1 (Week 1) up to \fisit 16 (Week 8) during
`each treatment period ]
`
`Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following
`a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another. prior to complete
`resolution. was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered
`one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks
`was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
`
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`Page 1 of 4
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`CSL EXHIBIT 1035
`CSL v. Shire
`
`

`

`525/2017
`
`Subcutaneous CIN RYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks - Full Text \fiew - ClinicalTrials.gov
`
`Secondary Outcome Measures:
`
`- Cumulative Attack-severity During the Treatment Period [Time Frame: From \fisit 1 (Week 1) up to \fisit 16 (Week 8) during each treatment
`period ]
`
`Cumulative Daily-severity During the Treatment Period [Time Frame: From Wait 1 (Week 1) up to WSit 16 (Week 8) during each treatment
`period ]
`
`Cumulative Daily-severity score was the sum of the severity scores recorded for every day of reported symptoms during the treatment
`period. Severity scores were recorded as None=0, Mild=1, Moderate=2, and Severe=3. None: no angioedema attack symptom; Mild: the
`angioedema attack symptom was noticeable to the participant but was easily tolerated and did not interfere with routine activities; Moderate:
`the angioedema attack symptom interfered with work/school or the abilty to participate in family life and social activities; Severe: the
`angioedema attack symptom significantly limited the participant's ability to attend work/school or participate in family life and social activities.
`Cumulative daily severity was normalized for the number of days participants participated in a given period and expressed as the monthly
`frequency. The scores ranged from 0 to 168 and higher scores represent worse symptoms.
`
`Cumulative Symptomatic Days During the Treatment Period [Time Frame: From Visit 1 (Week 1) up to Wait 16 (Week 8) during each
`treatment period ]
`
`Cumulative symptomatic days was defined as the sum of the symptomatic days of each angioedema attack reported during the treatment
`period. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. Cumulative symptomatic days
`was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
`
`Number of Angioedema Attacks Requiring Acute Treatment During the Treatment Period [Time Frame: From Visit 1 (Week 1) up to \fisit 16
`(Week 8) during each treatment period ]
`
`Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location folbwing
`a report of no swelfing or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete
`resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered
`one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks
`was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
`
`Cumulative Attack-severity score was the sum of maximum symptom severity recorded for each angioedema attack. determined on the last
`day of symptoms and recorded as None=0. Mild=1, Moderate=2. and Severe=3 and summing over the unique attacks. yields a Cumulative
`Attack-severity score. None: no angioedema attack symptom; Mild: the angioedema attack symptom was noticeable to the participant but
`was easily tolerated and did not interfere with routine activities; Moderate: the angioedema attack symptom interfered with work/school or the
`ability to participate In family Ife and social activities; Severe: the angloedema attack symptom significantly limited the participant's ability to
`attend work/school or participate in family life and social activities. Cumulative attack-severity was normalized for the number of days
`participants participated in a given period and expressed as the monthly frequency. The scores ranged from 0 to 168 and higher scores
`represent worse symptoms.
`
`https://cllrilcaltrlals.govlct2/show/NCT01756157
`
`47
`Enrollment:
`December 2012
`Study Start Date:
`September 2013
`Study Completion Date:
`Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
`
`Arms
`
`Experimental: SC CINRYZE with rHuPH20 Dose Level 1 followed by Dose Level 2
`sc CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks followed by so CINRYZE
`with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks.
`
`Experimental: SC CINRYZE with rHuPH20 Dose Level 2 followed by Dose Level 1
`SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE
`with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) far 8 weeks.
`
`Assigned Interventions
`
`Biological: CINRYZE
`with rHuPH20
`Other Names:
`- C1 esterase
`inhibitor (human)
`- Recombinant
`human
`hyaluronidase
`
`Biological: CINRYZE
`With THUPHZO
`Other Names:
`- C1 esterase
`inhibitor (human)
`- Recombinant
`human
`hyaluronidase
`
`Page 2 of 4
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`525/2017
`
`Subcutaneous CIN RYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks - Full Text \fiew - ClinicalTrials.gov
`
`D Eligibility
`
`Ages Eligible tor Study:
`Sexes Eligible for Study:
`Accepts Healthy Volunteers:
`Crlterla
`
`Inclusion Criteria:
`
`12 Years and older
`All
`No
`
`(Child, Adult. Senior)
`
`- Be 212 years of age.
`- Have a confirmed diagnosis of Hereditary Angioedema.
`Exclusion Criteria:
`
`- Receipt of any C1 inhibitor (C1 INH) therapy or any blood products for treatment or prevention of an angicedema attack within 7 days before
`the first dose of study drug.
`Be receiving prophylactic intravenous CINRYZE that exceeds 1000 units every 3 or 4 days (maximum weekly dose 2000 units).
`Have received any androgen therapy (e.g.. danazol, oxandrolone. stanczolol, testosterone) within 7 days prior to the first dose of study drug.
`If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e.,
`estrogen/progestin containing products) within 3 months prior to the first dose of study drug.
`History of allergic reaction to Ct INH products, including CINRYZE or other blood products.
`History of abnormal blood clotting.
`Have a known alergy to hyaluronidase or any other ingredient in the study formulation.
`
`' 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
`Informatlon. see Wigwam.
`
`Please refer to this study by its ClinicalTriaIS.gov identifier: NCT01756157
`
`:H Show 23 Study Locations
`
`Sponsors and Collaborators
`Shire
`
`Halozyme Therapeutics
`
`Investigators
`
`Study Director:
`
`Jennifer Schranz. MD WroPharma
`
`' More Information
`
`httpszllcllrtcalt’lals.govlct2/show/NCT01756157
`
`Shire
`Responsible Party:
`Clinical'l’rials.gov Identifier: NCT01756157
`Other Study ID Numbers:
`0624-206
`2012-000083-24 ( EudraCT Number )
`June 29, 2012
`May 29. 2015
`May 29. 2015
`
`Study First Received:
`Results First Received:
`Last Updated:
`
`History of Changes
`
`Keywords provided by Shire:
`Crossover
`Prevention
`Hereditary Angioedema
`C1 esterase inhibitor
`
`Additional relevant MeSH terms:
`
`C1 inhibitor
`Subcutaneous
`Recombinant human hyaluronidase
`
`Page 3 of 4
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`5/25/2017
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`Subcutaneols CINRYZE With Reoomblmrt Harm Hydu'onlchsefor Prevention ofAnooerbma Attacks - Full Text View - CllnlcalTrials.gov
`
`Angloedemas. Heredltary
`Angloedema
`Vascular Diseases
`Cardiovascular Dlseases
`Genetlc Dlseases. lnbom
`Urticeria
`Skin Diseases, Vascular
`Skin Diseases
`Hypersensitivity. Immediate
`
`Clinicarl'r'ials.gov processed this record on May 24. 2017
`
`Hypersensltlvlty
`Immune System Diseases
`Complement C1 lnhlbltor Protein
`Complement C1 lnactivator Proteins
`Complement C1s
`Complement lnactivating Agents
`Immunosuppressive Agents
`Immunologic Factors
`Physiological Effects of Drugs
`
`husz/cllricaltrlalsgwlcti’lshowlNCT01756157
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`Page 4 of 4
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