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出境医 / 临床实验 / Study to Compare How the Body Distributes and Excretes the Drugs Jivi (BAY 94-9027) and Adynovi in Patients With Severe Hemophilia A (Bleeding Disorder Resulting From a Lack of Blood Clotting Factor VIII)

Study to Compare How the Body Distributes and Excretes the Drugs Jivi (BAY 94-9027) and Adynovi in Patients With Severe Hemophilia A (Bleeding Disorder Resulting From a Lack of Blood Clotting Factor VIII)

Study Description
Brief Summary:

This study is being conducted to compare how the body distributes and excretes the drugs Jivi (BAY 94-9027) and Adynovi. Jivi is a recently approved blood clotting Factor VIII (FVIII) medication for the treatment of hemophilia A (bleeding disorder resulting from a lack of FVIII). Both drugs are FVIII products which have been manufactured via recombinant technology and have an extended half-live, i.e. they will stay longer in the body than other FVIII products. Therefore these products act longer in the body which reduces the frequency of drug injections. To compare the two drugs, a cross-over design was chosen, i.e. each patient will receive both products one after another.

Patients participating in this study will receive one dose of Jivi and one dose of Adynovi. Both drugs are injected into a vein. Observation will last for about 10 weeks, and blood samples will be taken from the participants to measure the blood levels of FVIII. Generic name of Jivi is Damoctocog-alfa-pegol, generic name of Adynovi is Rurioctocog alfa pegol.


Condition or disease Intervention/treatment Phase
Hemophilia A Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi) Biological: Rurioctocog alfa pegol (Adynovi) Phase 1

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single Dose, Open Label, Randomized, Cross-over Study in Participants With Severe Hemophilia A Comparing Pharmacokinetic Parameters of BAY 94-9027 and Adynovi
Actual Study Start Date : August 8, 2019
Actual Primary Completion Date : October 25, 2019
Actual Study Completion Date : January 29, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: BAY94-9027 / Adynovi
Treatment sequence A-B with washout before each treatment
 Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi)
Single dose, 50 IU/kg BAY94-9027 (IU: international Units)

Biological: Rurioctocog alfa pegol (Adynovi)
Single dose, 50 IU/kg Adynovi
Experimental: Adynovi / BAY94-9027
Treatment sequence B-A with washout before each treatment
 Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi)
Single dose, 50 IU/kg BAY94-9027 (IU: international Units)

Biological: Rurioctocog alfa pegol (Adynovi)
Single dose, 50 IU/kg Adynovi
Outcome Measures
Primary Outcome Measures :
  1. Area under the concentration versus time curve from time 0 to the last data point (AUC(0-tlast)) for BAY 94-9027 [ Time Frame: Pre-dose to 120 hours after the end of the infusion ]
  2. Area under the concentration versus time curve from time 0 to the last data point (AUC(0-tlast)) for Adynovi [ Time Frame: Pre-dose to 120 hours after the end of the infusion ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with severe hemophilia A (baseline FVIII activity FVIII:C <1%), determined by measurement at the time of screening (following a washout period of at least 72 h after their last FVIII treatment for standard half-life FVIII products or of 120 h for extended half-life FVIII products) or from reliable prior documentation (e.g. measurement in other clinical studies, result from approved clinical laboratory or diagnostic genetic testing).
  • ≥150 exposure days with FVIII concentrate(s) (plasma-derived or recombinant) as supported by medical records.
  • Body mass index (BMI) within the range 18 kg/m2 to 29.9 kg/m2 (inclusive).

Exclusion Criteria:

  • Inability to stop FVIII treatment to complete a minimum of 72 h washout for standard half-life FVIII product or 120 h washout for extended half-life FVIII product
  • Evidence of current or past inhibitor antibody
  • History of any congenital or acquired coagulation disorders other than hemophilia A
  • Platelet count <75,000/mm3
  • Human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4+) lymphocyte count of <200/mm3
  • Abnormal renal function (serum creatinine >2x the upper limit of the normal range [ULN])
  • Active liver disease verified by medical history or persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5x ULN or severe liver disease as evidenced by, but not limited to any of the following: International Normalized Ratio >1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices
  • Requirement of any pre-medication to tolerate FVIII treatment (e.g. anti-histamines)
  • Prior treatment with immunomodulatory agents or chemotherapy within the last 3 months prior to study entry or requirement of treatment during the study. The following drugs are allowed: α interferon, PEG interferon, highly active anti-retroviral therapy for HIV, and/or a total of two courses of pulse treatment with steroid for a maximum of 7 days at 1 mg/kg or less
Contacts and Locations

Locations
Layout table for location information
Bulgaria
SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD
Sofia, Bulgaria, 1756
Sponsors and Collaborators
Bayer
Tracking Information
First Submitted Date  ICMJE July 9, 2019
First Posted Date  ICMJE July 11, 2019
Last Update Posted Date December 21, 2020
Actual Study Start Date  ICMJE August 8, 2019
Actual Primary Completion Date October 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
  • Area under the concentration versus time curve from time 0 to the last data point (AUC(0-tlast)) for BAY 94-9027 [ Time Frame: Pre-dose to 120 hours after the end of the infusion ]
  • Area under the concentration versus time curve from time 0 to the last data point (AUC(0-tlast)) for Adynovi [ Time Frame: Pre-dose to 120 hours after the end of the infusion ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Compare How the Body Distributes and Excretes the Drugs Jivi (BAY 94-9027) and Adynovi in Patients With Severe Hemophilia A (Bleeding Disorder Resulting From a Lack of Blood Clotting Factor VIII)
Official Title  ICMJE Single Dose, Open Label, Randomized, Cross-over Study in Participants With Severe Hemophilia A Comparing Pharmacokinetic Parameters of BAY 94-9027 and Adynovi
Brief Summary

This study is being conducted to compare how the body distributes and excretes the drugs Jivi (BAY 94-9027) and Adynovi. Jivi is a recently approved blood clotting Factor VIII (FVIII) medication for the treatment of hemophilia A (bleeding disorder resulting from a lack of FVIII). Both drugs are FVIII products which have been manufactured via recombinant technology and have an extended half-live, i.e. they will stay longer in the body than other FVIII products. Therefore these products act longer in the body which reduces the frequency of drug injections. To compare the two drugs, a cross-over design was chosen, i.e. each patient will receive both products one after another.

Patients participating in this study will receive one dose of Jivi and one dose of Adynovi. Both drugs are injected into a vein. Observation will last for about 10 weeks, and blood samples will be taken from the participants to measure the blood levels of FVIII. Generic name of Jivi is Damoctocog-alfa-pegol, generic name of Adynovi is Rurioctocog alfa pegol.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia A
Intervention  ICMJE
  • Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi)
    Single dose, 50 IU/kg BAY94-9027 (IU: international Units)
  • Biological: Rurioctocog alfa pegol (Adynovi)
    Single dose, 50 IU/kg Adynovi
Study Arms  ICMJE
  • Experimental: BAY94-9027 / Adynovi
    Treatment sequence A-B with washout before each treatment
    Interventions:
    • Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi)
    • Biological: Rurioctocog alfa pegol (Adynovi)
  • Experimental: Adynovi / BAY94-9027
    Treatment sequence B-A with washout before each treatment
    Interventions:
    • Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi)
    • Biological: Rurioctocog alfa pegol (Adynovi)
Publications * Solms A, Shah A, Berntorp E, Tiede A, Iorio A, Linardi C, Ahsman M, Mancuso ME, Zhivkov T, Lissitchkov T. Direct comparison of two extended half-life PEGylated recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A. Ann Hematol. 2020 Nov;99(11):2689-2698. doi: 10.1007/s00277-020-04280-3. Epub 2020 Sep 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 9, 2019) 		18
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 29, 2020
Actual Primary Completion Date October 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants with severe hemophilia A (baseline FVIII activity FVIII:C <1%), determined by measurement at the time of screening (following a washout period of at least 72 h after their last FVIII treatment for standard half-life FVIII products or of 120 h for extended half-life FVIII products) or from reliable prior documentation (e.g. measurement in other clinical studies, result from approved clinical laboratory or diagnostic genetic testing).
  • ≥150 exposure days with FVIII concentrate(s) (plasma-derived or recombinant) as supported by medical records.
  • Body mass index (BMI) within the range 18 kg/m2 to 29.9 kg/m2 (inclusive).

Exclusion Criteria:

  • Inability to stop FVIII treatment to complete a minimum of 72 h washout for standard half-life FVIII product or 120 h washout for extended half-life FVIII product
  • Evidence of current or past inhibitor antibody
  • History of any congenital or acquired coagulation disorders other than hemophilia A
  • Platelet count <75,000/mm3
  • Human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4+) lymphocyte count of <200/mm3
  • Abnormal renal function (serum creatinine >2x the upper limit of the normal range [ULN])
  • Active liver disease verified by medical history or persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5x ULN or severe liver disease as evidenced by, but not limited to any of the following: International Normalized Ratio >1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices
  • Requirement of any pre-medication to tolerate FVIII treatment (e.g. anti-histamines)
  • Prior treatment with immunomodulatory agents or chemotherapy within the last 3 months prior to study entry or requirement of treatment during the study. The following drugs are allowed: α interferon, PEG interferon, highly active anti-retroviral therapy for HIV, and/or a total of two courses of pulse treatment with steroid for a maximum of 7 days at 1 mg/kg or less
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04015492
Other Study ID Numbers  ICMJE 19742
2018-000507-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bayer
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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