You are here

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%)

Last updated on October 9, 2019

FOR MORE INFORMATION
Study Location
General Hospital of Athens "Hippokration"
Athens, Attica, 11527 Greece
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Hemophilia B
Sex
Male
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-64 years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Males ≥ 18 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

- 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.

NCT03587116
Pfizer
Recruiting
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%)

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

call now

Try a new search

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.
Descriptive Information
Brief Title  ICMJE 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%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FIX:C?1%)
Official Title  ICMJE AN OPEN-LABEL, NON-INVESTIGATIONAL PRODUCT, LEAD-IN STUDY TO EVALUATE AT LEAST 6 MONTHS OF PROSPECTIVE EFFICACY AND SAFETY DATA OF FACTOR IX OR FACTOR VIII PROPHYLAXIS REPLACEMENT THERAPY IN THE USUAL CARE SETTING OF MODERATELY SEVERE TO SEVERE ADULT HEMOPHILIA B SUBJECTS (FIX:C?2%) WHO ARE NEGATIVE FOR nAb TO AAV VECTOR-SPARK100 AND MODERATELY SEVERE TO SEVERE HEMOPHILIA A ADULT SUBJECTS (FVIII:C?1%) WHO ARE NEGATIVE FOR nAb to AAV VECTOR SB-525 CAPSID (AAV6), PRIOR TO THE RESPECTIVE THERAPEUTIC PH 3 GENE THERAPY STUDIES (See Detailed Description Section for Official Protocol Title)
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.

To establish a minimum of 6 months of prospective efficacy data of current FVIII prophylaxis replacement therapy in the usual care setting of hemophilia A subjects, who are negative for nAb to SB-525 capsid (AAV6), prior to the Phase 3 gene therapy study.

The enrollment for hemophilia B participants is completed. At this time participants are only being enrolled for hemophilia A cohort.

Detailed DescriptionAN OPEN-LABEL, NON-INVESTIGATIONAL PRODUCT, MULTI-CENTER, LEAD-IN STUDY TO EVALUATE AT LEAST 6 MONTHS OF PROSPECTIVE EFFICACY AND SELECTED SAFETY DATA OF CURRENT FACTOR IX (FIX) OR FACTOR VIII (FVIII) 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 TO ADENO-ASSOCIATED VIRUS VECTOR-SPARK100 (BENEGENE-1) AND MODERATELY SEVERE TO SEVERE HEMOPHILIA A ADULT SUBJECTS (FVIII:C?1%) WHO ARE NEGATIVE FOR NEUTRALIZING ANTIBODIES TO ADENO-ASSOCIATED VIRUS VECTOR SB-525 CAPSID (AAV6), PRIOR TO THE RESPECTIVE THERAPEUTIC PHASE 3 GENE THERAPY STUDIES
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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

Condition  ICMJE
  • Hemophilia B
  • Hemophilia A
Intervention  ICMJE
  • 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.
  • Drug: Standard of Care FVIII Replacement therapy
    There is no investigational product being administered. Subjects will be administering their own standard of care FVIII replacement therapy.
Study Arms  ICMJE
  • Standard of Care FIX replacement therapy
    Intervention: Drug: Standard of Care FIX Replacement therapy
  • Standard of Care FVIII replacement therapy
    Intervention: Drug: Standard of Care FVIII Replacement therapy
Publications *Not Provided


*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 6, 2019)
250
Original Estimated Enrollment  ICMJE
 (submitted: July 2, 2018)
110
Estimated Study Completion Date  ICMJE October 5, 2021
Estimated Primary Completion DateOctober 5, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Hemophilia B Population:

  1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  2. Willing and able to comply with scheduled visits, FIX prophylaxis treatment plan, laboratory tests and other study procedures.
  3. Males ? 18 and <65 years of age with moderately severe to severe hemophilia B and documented FIX activity (?2%) prior to baseline visit.
  4. 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).
  5. Subjects 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.
  6. No known hypersensitivity to FIX replacement product.
  7. No history of FIX inhibitor (clinical or laboratory-based assessment) defined as a titer

    • 0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay. Clinically, no signs or symptoms of decreased response to FIX administration. Subjects will not be required to undergo diagnostic evaluation of inhibitor status to participate in the study.

Hemophilia A Population:

  1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  2. Willing and able to comply with scheduled visits, FVIII prophylaxis treatment plan, laboratory tests and other study procedures.
  3. Males ?18 and <65 years of age with moderately severe to severe hemophilia A and documented FVIII activity (?1%) prior to baseline visit.
  4. Previous experience with FVIII therapy (?150 documented exposure days to a FVIII protein product such as recombinant, plasma-derived or extended half-life FVIII product).
  5. Subjects on FVIII prophylaxis replacement therapy (recombinant, plasma-derived or extended half-life FVIII product) must have the intention to remain on FVIII prophylaxis replacement therapy for the duration of the study.
  6. No known hypersensitivity to FVIII replacement product.
  7. No history of FVIII inhibitor (clinical or laboratory-based assessment) defined as a titer ?0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay. Clinically, no signs or symptoms of decreased response to FVIII administration. Subjects will not be required to undergo diagnostic evaluation of inhibitor status to participate in the study.

Exclusion Criteria:

  1. Anti-AAV-Spark100 neutralizing antibody titer above or equal to 1:1 performed by a central laboratory during screening in hemophilia B subjects or Anti- SB-525 capsid (AAV6) neutralizing antibody titer (above or equal to the lowest detectable titer) performed by a central laboratory during screening in hemophilia A subjects.
  2. Lack of patient compliance with documentation of bleeds and/or prophylaxis replacement therapy administration.
  3. If there is no documentation regarding hepatitis status, as defined below, within the last 12 months prior to screening for hepatitis B and 6 months prior to screening for hepatitis C, then subjects will be required to have the following hepatitis testing performed at screening:

    1. Hepatitis B screening (acute and chronic):

      HBsAg (also referred to as Hepatitis B surface antigen), HBV-DNA viral assay (also referred to as a nucleic acid test for Hepatitis B virus DNA), and Anti-HBc (also referred to as Total Hepatitis B core antibody).

      • A subject is not eligible if either HbsAg is positive or HBV-DNA is positive/detectable.
      • Anti-HBc must be obtained in all subjects for determination of whether the subject had prior hepatitis B. If the anti-HBc is positive and both HBsAg and HBV DNA are negative this would be consistent with a prior infection and the subject would be eligible for the study. Anti-HBc must be obtained in all subjects to discriminate between those with no prior hepatitis B and those with prior infection in the event of reactivation. FDA has noted reactivation of hepatitis B virus exists.
      • One documented negative HBV-DNA viral load is sufficient to assess eligibility. A subject who is currently undergoing anti-viral therapy for hepatitis B is not eligible.
    2. Hepatitis C (acute or chronic):

      • A subject who is currently undergoing anti-viral therapy for chronic hepatitis C is not eligible.
      • Subjects treated with anti-viral therapy for chronic hepatitis C, must have completed anti-viral therapy at least 6 months prior to screening and have a negative HCV-RNA at least 6 months prior to screening.
      • All subjects (who are not currently undergoing anti-viral therapy for chronic hepatitis C) must have a single HCV-RNA load assay (also referred to as a nucleic acid test [NAT] for HCV RNA) obtained during the 6 months preceding screening. This includes subjects with prior known chronic hepatitis C who have completed treatment with anti-viral therapy.
      • A subject is not eligible if his HCV-RNA load assay result is positive/detectable.
  4. Currently on antiviral therapy for hepatitis B or C.
  5. 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.

    All subjects who do not have the listed pre-existing diagnoses above must have the following assessments performed within the last 12 months prior to screening and if not will need to be tested for liver fibrosis status at screening:

    • Measurement of serum albumin. A subject is not eligible if the serum albumin level is below the testing laboratory's lower limit of normal; and
    • One of the following diagnostic tests for liver fibrosis. The following results are indicative of fibrosis 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.

      • Please note, if a subject has a known history of Gilbert's syndrome, a FibroTest cannot be used for fibrosis testing.
  6. 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. Subjects who are HIV positive and stable, have an adequate CD4 count (>200/mm3) and undetectable viral load (<50 gc/mL) documented within the preceding 12 months, and are on an antiretroviral drug regimen are eligible to enroll. Subjects who have not been tested within the prior 12 months of screening will need to be tested for HIV status at screening.
  7. 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.
  8. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation or other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  9. 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.
  10. Any subject who previously received fidanacogene elaparvovec (SPK-9001) (hemophilia B) or SB-525 (hemophilia A) or any AAV gene-based therapy.
  11. Any subject with a planned surgical procedure requiring FIX (hemophilia B) or FVIII (hemophilia A) surgical prophylactic factor treatment in the next 24 months.
  12. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study:Male
Gender Based Eligibility:Yes
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Canada,   France,   Germany,   Greece,   Israel,   Italy,   Japan,   Korea, Republic of,   Saudi Arabia,   Spain,   Sweden,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03587116
Other Study ID Numbers  ICMJE C0371004
2017-001271-23 ( EudraCT Number )
NAB PROTOCOL ( Other Identifier: Alias Study Number )
Has Data Monitoring CommitteeNot Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product:Yes
Studies a U.S. FDA-regulated Device Product:No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/da....
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/da...
Responsible PartyPfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS AccountPfizer
Verification DateAugust 2019

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

BY PHONE

Pfizer Clinical Trials Contact Center

1-800-718-1021

BY EMAIL

Contact

[email protected]

Call Now