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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03587116




Registration number
NCT03587116
Ethics application status
Date submitted
29/06/2018
Date registered
16/07/2018

Titles & IDs
Public 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%)
Scientific title
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)
Secondary ID [1] 0 0
2017-001271-23
Secondary ID [2] 0 0
C0371004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia B 0 0
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Standard of Care FIX Replacement therapy
Treatment: Drugs - Standard of Care FVIII Replacement therapy

Other: Standard of Care FIX replacement therapy -

Other: Standard of Care FVIII replacement therapy -


Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized bleeding rate (ABR)
Timepoint [1] 0 0
6 months
Primary outcome [2] 0 0
Incidence of serious adverse events
Timepoint [2] 0 0
6 months
Primary outcome [3] 0 0
Events of special interest (ESI):inhibitor against FIX or FVIII, thrombotic events, and FIX or FVIII hypersensitivity reactions
Timepoint [3] 0 0
6 months
Secondary outcome [1] 0 0
Annualized infusion rate (AIR)
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Dose and total factor consumption
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Number of bleeding events (spontaneous and/or traumatic)
Timepoint [3] 0 0
6 months

Eligibility
Key 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 must be on a stable FVIII prophylaxis replacement therapy (recombinant, plasma-derived or extended half-life FVIII product) at study entry and must have the intention to remain on FVIII prophylaxis replacement therapy for the duration of the study. This does not include nonfactor treatments, which are prohibited.
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.
Minimum age
18 Years
Maximum age
64 Years
Sex
Males
Can healthy volunteers participate?
No
Key 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 median stiffness 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. Participants using restricted therapies.
12. Any participant with a planned surgical procedure requiring FIX (hemophilia B) or FVIII (hemophilia A) surgical prophylactic factor treatment in the next 24 months.
13. 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).

Study design
Purpose of the study
Other
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/07/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
18/09/2024
Actual
Sample size
Target
Accrual to date
Final
213
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Mississippi
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Belgium
State/province [9] 0 0
Brussels
Country [10] 0 0
Brazil
State/province [10] 0 0
Espirito Santo
Country [11] 0 0
Brazil
State/province [11] 0 0
Para
Country [12] 0 0
Brazil
State/province [12] 0 0
SAO Paulo
Country [13] 0 0
Brazil
State/province [13] 0 0
SÃO Paulo
Country [14] 0 0
Brazil
State/province [14] 0 0
Rio de Janeiro
Country [15] 0 0
Brazil
State/province [15] 0 0
São Paulo
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
France
State/province [17] 0 0
Brest
Country [18] 0 0
France
State/province [18] 0 0
Bron
Country [19] 0 0
France
State/province [19] 0 0
Nantes Cedex 1
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
Bonn
Country [23] 0 0
Germany
State/province [23] 0 0
Frankfurt/Main
Country [24] 0 0
Germany
State/province [24] 0 0
Giessen
Country [25] 0 0
Germany
State/province [25] 0 0
Homburg/Saar
Country [26] 0 0
Greece
State/province [26] 0 0
Attica
Country [27] 0 0
Israel
State/province [27] 0 0
Tel-Hashomer
Country [28] 0 0
Italy
State/province [28] 0 0
BO
Country [29] 0 0
Italy
State/province [29] 0 0
Firenze
Country [30] 0 0
Italy
State/province [30] 0 0
Napoli
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
Japan
State/province [32] 0 0
Aichi
Country [33] 0 0
Japan
State/province [33] 0 0
Hokkaido
Country [34] 0 0
Japan
State/province [34] 0 0
Nara
Country [35] 0 0
Japan
State/province [35] 0 0
Saitama
Country [36] 0 0
Japan
State/province [36] 0 0
Tokyo
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Daegu
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul
Country [39] 0 0
Saudi Arabia
State/province [39] 0 0
Riyadh
Country [40] 0 0
Spain
State/province [40] 0 0
Murcia
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Spain
State/province [43] 0 0
Valladolid
Country [44] 0 0
Sweden
State/province [44] 0 0
Malmö
Country [45] 0 0
Taiwan
State/province [45] 0 0
Changhua
Country [46] 0 0
Taiwan
State/province [46] 0 0
Kaohsiung
Country [47] 0 0
Taiwan
State/province [47] 0 0
Taichung City
Country [48] 0 0
Taiwan
State/province [48] 0 0
Taichung
Country [49] 0 0
Taiwan
State/province [49] 0 0
Taipei City
Country [50] 0 0
Taiwan
State/province [50] 0 0
Taipei
Country [51] 0 0
Turkey
State/province [51] 0 0
I?zmir
Country [52] 0 0
Turkey
State/province [52] 0 0
Adana
Country [53] 0 0
Turkey
State/province [53] 0 0
Antalya
Country [54] 0 0
Turkey
State/province [54] 0 0
Gaziantep
Country [55] 0 0
Turkey
State/province [55] 0 0
Istanbul
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Tyne & Wear
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Glasgow
Country [58] 0 0
United Kingdom
State/province [58] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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/data_requests.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03587116