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)

NCT04015492 | Completed Phase 1 FDA Drug

• 2 other identifiers: 197422018-000507-16
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (2)

• Area under the concentration versus time curve from time 0 to the last data point (AUC(0-tlast)) for BAY 94-9027

  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

  Pre-dose to 120 hours after the end of the infusion

Study Arms (2)

BAY94-9027 / Adynovi

EXPERIMENTAL

Treatment sequence A-B with washout before each treatment

Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi); Biological: Rurioctocog alfa pegol (Adynovi)

Adynovi / BAY94-9027

EXPERIMENTAL

Treatment sequence B-A with washout before each treatment

Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi); Biological: Rurioctocog alfa pegol (Adynovi)

Interventions

Damoctocog-alfa-pegol (BAY94-9027, Jivi) BIOLOGICAL

Single dose, 50 IU/kg BAY94-9027 (IU: international Units)

Adynovi / BAY94-9027; BAY94-9027 / Adynovi

Rurioctocog alfa pegol (Adynovi) BIOLOGICAL

Single dose, 50 IU/kg Adynovi

Adynovi / BAY94-9027; BAY94-9027 / Adynovi

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD

Sofia, 1756, Bulgaria

Location

Related Publications (1)

• 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.

  PMID: 32974838 DERIVED

Related Links

• Click here to find results for studies related to Bayer products

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; BAX 855

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

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 11, 2019
• Study Start: August 8, 2019
• Primary Completion: October 25, 2019
• Study Completion: January 29, 2020
• Last Updated: December 21, 2020

Record last verified: 2020-12

Locations

BU (1)