ClinicalTrials.gov
ClinicalTrials.gov Menu

Six Month lead-in Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03587116
Recruitment Status : Recruiting
First Posted : July 16, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
To establish a minimum of 6 months of prospective efficacy data of current FIX prophylaxis replacement therapy in the usual care setting of hemophilia B subjects, who are negative for NAb to AAV-Spark100, prior to the Phase 3 gene therapy study.

Condition or disease Intervention/treatment Phase
Hemophilia B Drug: Standard of Care FIX Replacement therapy Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Intervention Model: Single Group Assignment
Intervention Model Description: The data obtained from this 6 month lead-in study will serve as the control group for the subsequent Phase 3 gene therapy study.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open-label, Non-investigational Product, Multi-center, Lead-in Study To Evaluate At Least 6 Months Of Prospective Efficacy And Selected Safety Data Of Factor Ix (Fix) Prophylaxis Replacement Therapy In The Usual Care Setting Of Moderately Severe To Severe Adult Hemophilia B Subjects (Fix:c≤2%) Who Are Negative For Neutralizing Antibodies (Nab) To Adeno-associated Virus Vector (Aav)-spark100
Actual Study Start Date : July 26, 2018
Estimated Primary Completion Date : November 16, 2020
Estimated Study Completion Date : November 16, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Standard of Care FIX replacement therapy Drug: Standard of Care FIX Replacement therapy
There is no investigational product being administered. Subjects will be administering their own standard of care FIX replacement therapy.




Primary Outcome Measures :
  1. Annualized bleeding rate (ABR) [ Time Frame: 6 months ]
    The annualized bleeding rate (ABR) per subject will be calculated as the number of bleeds over number of days subject received FIX prophylaxis replacement therapy from baseline visit (Day 1) to end of study x 365.25 days. ABR will be summarized using descriptive statistics (n, mean, standard deviation, median, Q1, Q3, minimum, maximum).

  2. Incidence of serious adverse events [ Time Frame: 6 months ]
    The primary safety analysis will be performed on all subjects that sign the informed consent document and are subsequently identified as nAb negative and are enrolled (complete baseline visit) into the study.

  3. Events of special interest (ESI):inhibitor against FIX, thrombotic events, and FIX hypersensitivity reactions [ Time Frame: 6 months ]
    Frequency and percentage of these ESI events will be summarized by event. In addition any events leading to discontinuation from the study will be described.


Secondary Outcome Measures :
  1. Annualized infusion rate (AIR) [ Time Frame: 6 months ]
    The annualized infusion rate (AIR) per subject will be calculated as the number of infusions received over number of days subject received FIX prophylaxis replacement therapy from baseline visit (Day 1) to end of study x 365.25 days. AIR will be summarized using descriptive statistics (n, mean, standard deviation, median, Q1, Q3, minimum, maximum).

  2. Dose and total factor consumption [ Time Frame: 6 months ]
    The total factor IX replacement therapy consumption and the corresponding dose will be descriptively summarized by the categories of the replacement therapy, where appropriate. Infusion diary (electronic infusion diary) of the factor IX replacement therapy will be listed.

  3. Number of bleeding events (spontaneous and/or traumatic) [ Time Frame: 6 months ]
    The number of bleeding episodes will be summed up by spontaneous, traumatic and overall as defined as any bleed occurring >72 hours after stopping treatment from the original bleed for which treatment was initiated or a bleed occurring at a different site from the original bleed regardless of the time from last injection.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males ≥ 18 and < 65 years of age with moderate severe to severe hemophilia B and documented FIX activity (≤2%) within the last 12 months prior to baseline visit.
  • Willing and able to comply with scheduled visits, FIX prophylaxis treatment plan, laboratory tests and other study procedures.
  • Previous experience with FIX therapy (≥50 documented exposure days to a FIX protein product such as recombinant, plasma-derived or extended half-life FIX product)
  • Subjects as per usual care setting on FIX prophylaxis replacement therapy (recombinant, plasma-derived or extended half-life FIX product) must have the intention to remain on FIX prophylaxis replacement therapy for the duration of the study
  • No known hypersensitivity to FIX replacement product
  • No history of FIX inhibitor (clinical or laboratory-based assessment) defined as a titer ≥ to 0.6 BU/mL

Exclusion Criteria:

  • Anti-AAV-Spark100 neutralizing antibodies titer (above the lowest detectable titer) performed by a central laboratory during screening.
  • Lack of patient compliance with documentation of bleeds and/or FIX prophylaxis replacement therapy administration.
  • A subject is not eligible if either HbsAg is positive or HBV-DNA is positive/detectable.
  • A subject who is currently undergoing anti-viral therapy for hepatitis B is not eligible
  • A subject who is currently undergoing anti-viral therapy for chronic hepatitis C is not eligible.
  • A subject is not eligible if his HCV-RNA load assay result is positive/detectable.
  • Currently on antiviral therapy for hepatitis B or C.
  • A subject is not eligible if any of the following pre-existing diagnoses, which are indicative of significant underlying liver disease, are present in the medical record:

    • Portal hypertension; or
    • Splenomegaly; or
    • Hepatic encephalopathy
  • A subject is not eligible if the serum albumin level is below the testing laboratory's lower limit of normal; and

    • At least one of the following diagnostic tests for liver fibrosis indicating ≥ stage 3. The following results are indicative of fibrosis ≥ stage 3 and exclude the subject from participation:
    • FibroScan, with a score >8.3 kPa units;
    • FibroTest/FibroSURE with a result >0.48; or
    • AST-to-Platelet Ratio Index (APRI) >1.
  • Documented serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with Cluster of Differentiation 4 positive (CD4+) cell count ≤200 mm3 within the last 12 months prior to screening.
  • History of chronic infection or other chronic disease that the investigator deems an unacceptable risk. Any patient with a history of thrombotic events including but not limited to stroke or myocardial infarction. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation.
  • Participation in other studies involving investigational drug(s) within the last 3 months prior to study entry and/or during study participation or in a previous gene therapy clinical study within the last 12 months prior to screening.
  • Any subject with a planned surgical procedure requiring FIX surgical prophylactic factor treatment in the next 24 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03587116


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
United States, California
University of California San Francisco - UCSF HTC Not yet recruiting
San Francisco, California, United States, 94117
University of California, San Francisco Not yet recruiting
San Francisco, California, United States, 94117
University of California, San Francisco - Clinical Research Center Not yet recruiting
San Francisco, California, United States, 94143
University of California, San Francisco - Outpatient Hematology Clinic Not yet recruiting
San Francisco, California, United States, 94143
United States, Mississippi
Mississippi Center for Advanced Medicine Recruiting
Madison, Mississippi, United States, 39110
United States, Nevada
Alliance for Childhood Diseases/Cure 4 the Kids Foundation Not yet recruiting
Las Vegas, Nevada, United States, 89135
United States, Washington
Bloodworks NW Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03587116     History of Changes
Other Study ID Numbers: C0371004
2017-001271-23 ( EudraCT Number )
NAB PROTOCOL ( Other Identifier: Alias Study Number )
First Posted: July 16, 2018    Key Record Dates
Last Update Posted: November 2, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked