Brief Title
A 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 (FVIII:C≤1%)
Official Title
AN OPEN-LABEL, NON-INVESTIGATIONAL PRODUCT, MULTI-CENTER, LEAD-IN STUDY TO EVALUATE 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 NEUTRALIZING 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 baseline 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 baseline prospective efficacy data of current FVIII prophylaxis replacement
therapy in the usual care setting of hemophilia A subjects, who are negative for nAb to AAV6,
prior to the Phase 3 gene therapy study.
The enrollment for hemophilia A participants is completed. At this time participants are only
being enrolled for hemophilia B cohort.
Detailed Description
AN OPEN-LABEL, NON-INVESTIGATIONAL PRODUCT, MULTI-CENTER, LEAD-IN STUDY TO EVALUATE
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 6 (AAV6), PRIOR TO THE RESPECTIVE THERAPEUTIC PHASE 3 GENE
THERAPY STUDIES
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Annualized bleeding rate (ABR)
Secondary Outcome
Annualized infusion rate (AIR)
Condition
Hemophilia B
Intervention
Standard of Care FIX Replacement therapy
Study Arms / Comparison Groups
Standard of Care FIX replacement therapy
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
250
Start Date
July 26, 2018
Completion Date
November 8, 2023
Primary Completion Date
November 8, 2023
Eligibility Criteria
Inclusion Criteria:
Hemophilia B Population:
1. Evidence of a signed and dated informed consent document indicating that the
participant 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. Participants 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. Participants will not be required to undergo diagnostic
evaluation of inhibitor status to participate in the study.
Hemophilia A Population:
1. Evidence of a signed and dated informed consent document indicating that the
participant 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. Participants 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. Participants 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 the established threshold
performed by a central laboratory during screening in hemophilia B subjects or
Anti-AAV6 neutralizing antibody titer above the established threshold performed by a
central laboratory during screening in hemophilia A subjects.
2. Lack of participant 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 participants 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 participant is not eligible if either HbsAg is positive or HBV-DNA is
positive/detectable.
- Anti-HBc must be obtained in all participants for determination of whether
the participant 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 participant who is currently undergoing anti-viral therapy
for hepatitis B is not eligible.
2. Hepatitis C (acute or chronic):
- A participant who is currently undergoing anti-viral therapy for chronic
hepatitis C is not eligible.
- Participants 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 participants (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 participants with prior known chronic
hepatitis C who have completed treatment with anti-viral therapy.
- A participant is not eligible if his HCV-RNA load assay result is
positive/detectable.
4. Currently on antiviral therapy for hepatitis B or C.
5. Significant liver disease, as defined by pre-existing diagnosis of portal
hypertension, splenomegaly, or hepatic encephalopathy.
All participants 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: a serum albumin
level below normal limits and/or significant liver fibrosis by any of the following
diagnostic modalities: FibroScan score >8 kPa units OR FibroTest/FibroSURE >0.48*.
* NOTE: If there is concern regarding the validity of any of the liver fibrosis test
results please contact the medical monitor to discuss whether any additional testing
needs to be performed (ie, either repeating any test or performing another fibrosis
test). Also, note, if a participant 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. Participants 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. Participants 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. In addition, any participant with conditions associated with
increased thromboembolic risk such as known inherited or acquired thrombophilia, or a
history of thrombotic events including but not limited to stroke, myocardial
infarction, and/or venous thromboembolism, is excluded.
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 participant inappropriate for entry into
this study. In addition, any participant with a history of a neoplasm (including
hepatic malignancy) that required treatment (eg, chemotherapy, radiotherapy,
immunotherapy), is excluded, except for adequately treated basal or squamous cell
carcinoma of the skin or a surgically removed benign neoplasm not requiring
chemotherapy, radiotherapy and/or immunotherapy. Any other neoplasm that has been
cured by resection should be discussed between the investigator and sponsor.
9. Participation in other studies if involving administration of investigational
product(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.
• Participants already enrolled in this lead-in study (C0371004) may be allowed to
participate in the screening and baseline periods of either C0371002 or C3731003
protocols prior to their completion of the end of study visit in this lead-in study.
10. Any participant who previously received fidanacogene elaparvovec (hemophilia B) or
giroctocogene fitelparvovec (hemophilia A) or any AAV gene-based therapy.
11. Any participant 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
participants who are Pfizer employees, including their family members, directly
involved in the conduct of the study.
NOTE: The sponsor's medical team should be contacted if there are any questions regarding
any of the inclusion or exclusion criteria (Sections: 4.1 and 4.2).
Gender
Male
Ages
18 Years - 64 Years
Accepts Healthy Volunteers
No
Contacts
Pfizer CT.gov Call Center, 1-800-718-1021, [email protected]
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03587116
Organization ID
C0371004
Secondary IDs
2017-001271-23
Responsible Party
Sponsor
Study Sponsor
Pfizer
Study Sponsor
Pfizer CT.gov Call Center, Study Director, Pfizer
Verification Date
March 2023