History of Changes for Study: NCT03587116

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%)

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Study Record Versions

Version	Submitted Date	Changes
1	July 2, 2018	None (earliest Version on record)
2	August 31, 2018	Recruitment Status, Arms and Interventions, Study Status, Oversight and Contacts/Locations
3	October 4, 2018	Contacts/Locations and Study Status
4	November 1, 2018	Study Status and Contacts/Locations
5	December 10, 2018	Contacts/Locations and Study Status
6	January 4, 2019	Contacts/Locations, IPDSharing, Study Status and Study Identification
7	February 4, 2019	Contacts/Locations and Study Status
8	March 3, 2019	References, Contacts/Locations and Study Status
9	April 2, 2019	Study Status and Contacts/Locations
10	May 1, 2019	Contacts/Locations and Study Status
11	June 3, 2019	Study Status and Contacts/Locations
12	July 3, 2019	Contacts/Locations and Study Status
13	August 6, 2019	Contacts/Locations, Study Status, Outcome Measures, Arms and Interventions, Study Description, Study Identification, References, Eligibility, Study Design and Conditions
14	October 27, 2019	References, Contacts/Locations and Study Status
15	December 2, 2019	Study Status and Contacts/Locations
16	February 26, 2020	Study Status and Contacts/Locations
17	April 14, 2020	Study Status, Contacts/Locations and Study Identification
18	June 3, 2020	Study Status and Contacts/Locations
19	July 17, 2020	Contacts/Locations and Study Status
20	August 16, 2020	Contacts/Locations and Study Status
21	October 12, 2020	Study Status and Contacts/Locations
22	December 8, 2020	Contacts/Locations, Study Status and Study Identification
23	January 25, 2021	Study Status, Contacts/Locations and Study Identification
24	March 2, 2021	Contacts/Locations and Study Status
25	April 19, 2021	Contacts/Locations and Study Status
26	June 12, 2021	Study Status, Contacts/Locations, Eligibility and Study Identification
27	July 14, 2021	Study Status, Contacts/Locations, Study Description and Study Identification
28	August 25, 2021	Study Status, Contacts/Locations and Study Identification
29	October 18, 2021	Study Status, Contacts/Locations and Study Identification
30	December 2, 2021	Study Status and Contacts/Locations
31	December 10, 2021	Contacts/Locations and Study Status
32	February 4, 2022	Recruitment Status, Study Status, Contacts/Locations, Study Design and Study Identification
33	March 10, 2022	Recruitment Status, Study Status, Contacts/Locations, Study Design and Study Identification
34	April 14, 2022	Contacts/Locations and Study Status
35	September 13, 2022	Contacts/Locations, Study Design, Study Description, Study Status, Study Identification and Eligibility
36	October 4, 2022	Contacts/Locations and Study Status
37	November 16, 2022	Contacts/Locations, Study Status and Study Design
38	December 5, 2022	Study Status and Contacts/Locations
39	December 29, 2022	Study Status and Contacts/Locations
40	February 6, 2023	Study Status and Contacts/Locations
41	March 16, 2023	Study Status
42	April 12, 2023	Study Status and Contacts/Locations
43	May 17, 2023	Study Status and Contacts/Locations
44	June 5, 2023	Recruitment Status, Study Status, Contacts/Locations and Study Design
45	July 16, 2023	Study Status
46	August 21, 2023	Study Status
47	September 11, 2023	Study Status
48	March 19, 2024	Study Status and Eligibility
49	April 29, 2024	Study Status, Contacts/Locations and Study Identification

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	C0371004
Brief 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%)
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
Secondary IDs:	2017-001271-23 [EudraCT Number] NAB PROTOCOL [Alias Study Number]

Study Status


Record Verification:	July 2018
Overall Status:	Not yet recruiting
Study Start:	July 26, 2018
Primary Completion:	November 16, 2020 [Anticipated]
Study Completion:	November 16, 2020 [Anticipated]

First Submitted:	June 29, 2018
First Submitted that Met QC Criteria:	July 2, 2018
First Posted:	July 16, 2018 [Actual]

Last Update Submitted that Met QC Criteria:	July 2, 2018
Last Update Posted:	July 16, 2018 [Actual]

Sponsor/Collaborators


Sponsor:	Pfizer
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:

Study Description


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.
Detailed Description:

Conditions


Conditions:	Hemophilia B
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Other
Study Phase:	Phase 3
Interventional Study Model:	Single Group Assignment
	The data obtained from this 6 month lead-in study will serve as the control group for the subsequent Phase 3 gene therapy study.
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	110 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Standarad of Care FIX replacement therapy	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.

Outcome Measures


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.

Eligibility


Minimum Age:	18 Years
Maximum Age:	64 Years
Sex:	Male
Gender Based:	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.

Contacts/Locations


Central Contact Person:	Pfizer CT.gov Call Center Telephone: 1-800-718-1021 Email: ClinicalTrials.gov_Inquiries@pfizer.com
Study Officials:	Pfizer CT.gov Call Center Study Director Pfizer
Locations:

IPDSharing


Plan to Share IPD:	Yes 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
	Supporting Information:
	Time Frame:
	Access Criteria:
	URL: