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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03587116
Ethics application status
Date submitted
29/06/2018
Date registered
16/07/2018
Date last updated
8/08/2019

Titles & IDs
Public title
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%)
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) - 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).
The annualized bleeding rate (ABR) per subject will be calculated as the number of bleeds over number of days subject received FVIII 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).
Timepoint [1] 0 0
6 months
Primary outcome [2] 0 0
Incidence of serious adverse events - 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.
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 - 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.
Timepoint [3] 0 0
6 months
Secondary outcome [1] 0 0
Annualized infusion rate (AIR) - 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).
The annualized infusion rate (AIR) per subject will be calculated as the number of infusions received over number of days subject received FVIII 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).
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Dose and total factor consumption - 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.
The total factor VIII 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 VIII replacement therapy will be listed.
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Number of bleeding events (spontaneous and/or traumatic) - 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.
Timepoint [3] 0 0
6 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
64 Years
Gender
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Ronald Sawers Haemophilia Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
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
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Belgium
State/province [10] 0 0
Brussels
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
Rio de Janeiro
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
France
State/province [15] 0 0
Bron
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Bonn
Country [19] 0 0
Greece
State/province [19] 0 0
Attica
Country [20] 0 0
Israel
State/province [20] 0 0
Tel-Hashomer
Country [21] 0 0
Italy
State/province [21] 0 0
Firenze
Country [22] 0 0
Italy
State/province [22] 0 0
Napoli
Country [23] 0 0
Italy
State/province [23] 0 0
Roma
Country [24] 0 0
Japan
State/province [24] 0 0
Aichi
Country [25] 0 0
Japan
State/province [25] 0 0
Nara
Country [26] 0 0
Japan
State/province [26] 0 0
Tokyo
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Saudi Arabia
State/province [28] 0 0
Riyadh
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Spain
State/province [31] 0 0
Valencia
Country [32] 0 0
Sweden
State/province [32] 0 0
Malmö
Country [33] 0 0
Taiwan
State/province [33] 0 0
Kaohsiung
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taichung
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taipei
Country [36] 0 0
Turkey
State/province [36] 0 0
I?zmir
Country [37] 0 0
Turkey
State/province [37] 0 0
Adana
Country [38] 0 0
Turkey
State/province [38] 0 0
Antalya
Country [39] 0 0
Turkey
State/province [39] 0 0
Gaziantep
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Tyne & Wear
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Glasgow

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

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03587116
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
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
ClinicalTrials.gov_Inquiries@pfizer.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03587116