Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A

NCT02093897 | Completed Phase 3 Results DMC

• 2 other identifiers: CSL627_30022012-001336-65
• Study Type: interventional
• Target: 84
• Locations: 18 countries
• Sites: 36

Brief Summary

This is an international, multicenter, open-label study to assess the efficacy, safety, and pharmacokinetic (PK) profile of rVIII-SingleChain in pediatric patients with severe hemophilia A. A minimum of 25 previously treated subjects ≥ 6 to \< 12 years of age and at least 25 subjects \< 6 years of age who have undergone \> 50 exposure days (EDs) with a previous Factor VIII (FVIII) product are planned to be enrolled. Subjects will be assigned to either an on-demand or prophylaxis treatment regimen and will receive rVIII-SingleChain at a dose to be determined by the investigator. Hemostatic efficacy will be assessed by the subject/caregiver and the investigator who will assess overall efficacy by a 4-point scale.

Conditions

Congenital Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Treatment Success

  Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.

  Up to 1 year

Secondary Outcomes (12)

• Annualized Bleeding Rate

  Up to 1 year

• Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis.

  Up to 1 year

• Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month

  Up to 1 year

• Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year

  Up to 1 year

• Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event

  Up to 1 year

Study Arms (1)

rVIII-SingleChain

EXPERIMENTAL

Subjects will be assigned to either an on-demand or prophylaxis regimen and will receive rVIII-SingleChain as an intravenous (IV) infusion. Subjects assigned to a prophylaxis regimen will be treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode is based on the recommendations of the World Federation of Hemophilia (WFH), with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects will receive a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.

Biological: rVIII-SingleChain

Interventions

rVIII-SingleChain BIOLOGICAL

Also known as: Recombinant Factor VIII single chain, CSL627

rVIII-SingleChain

Eligibility Criteria

• Age: Up to 11 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of severe hemophilia A defined as \< 1% Factor VIII (FVIII) concentration (FVIII:C) documented in medical records,
• Males \< 12 years of age,
• Subjects who have received \> 50 EDs with a FVIII product,
• Prior PK data (at least incremental recovery and half-life) from previous FVIII exposure for subjects participating in the PK part
• Investigator believes that the subject is willing and able to adhere to all protocol requirements. Investigator believes that the subject's parent(s) or legally acceptable representative(s) is / are willing and able to adhere to all protocol requirements.

You may not qualify if:

• Any history of or current FVIII inhibitors
• Use of an Investigational Medical Product (IMP) within 30 days prior to the first rVIII-SingleChain administration,
• Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain,
• Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein,
• Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment,
• Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values \>5 times (x) the upper limit of normal (ULN) at Screening,
• Subjects with serum creatinine values \>2 x ULN at Screening,
• Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months before Day 1,
• Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months before rVIII-SingleChain administration.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (37)

Study Site

Aurora, Colorado, 80045, United States

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Chicago, Illinois, 60612, United States

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Melbourne, Victoria, 3052, Australia

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Linz, 4020, Austria

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Vienna, 1090, Austria

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Brest, 29609, France

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Le Kremlin-Bicêtre, 94270, France

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Lille, 59037, France

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Nantes, 44093, France

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Paris, 75015, France

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Tbilisi, 0177, Georgia

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Bonn, 53127, Germany

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Bremen, 28177, Germany

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Frankfurt am Main, 60590, Germany

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Hanover, 30159, Germany

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Milan, 20122, Italy

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Beirut, 11072240, Lebanon

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Kuala Lumpur, 50400, Malaysia

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Amsterdam, 1105 AZ, Netherlands

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Njmegen, 6525 GA, Netherlands

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Utrecht, 3584 CX, Netherlands

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Cebu City, 6000, Philippines

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Davao City, 8000, Philippines

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Rzeszów, 35-310, Poland

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Porto, 4202-451, Portugal

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Timișoara, 300011, Romania

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Madrid, 28046, Spain

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Lucerne, 6000, Switzerland

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Bangkok, 10330, Thailand

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Khon Kaen, 40002, Thailand

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Songkhla, 90110, Thailand

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Adana, 01330, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Lviv, 79044, Ukraine

Location

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Clinical Trial Disclosure Manager
• Organization: CSL Behring

clinicaltrials@cslbehring.com

Use email contact

Study Officials

• Program Director

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2014
• First Posted: March 21, 2014
• Study Start: March 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: January 27, 2017
• Results First Posted: January 27, 2017

Record last verified: 2016-12

Locations

GE (1); MY (1); US (2); AU (2); CH (1); ES (1); RO (1); TH (5); DE (4); TU (3); PT (1); UA (1); PL (1); IT (1); PH (2); FR (5); NL (3); LE (1)