A Gene Therapy Study for Hemophilia B

• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

A Phase 1/2, Open-Label, Non-Randomized, Dose-Escalation Study of SPK-9001 in Subjects with Hemophilia B.

Condition or disease	Intervention/treatment	Phase
Hemophilia B	Biological: SPK-9001	Phase 2

Detailed Description:

Hemophilia B, or Christmas disease, is a genetic bleeding disorder resulting in the lack of ability to produce blood-clotting factor IX (FIX). Individuals with hemophilia B suffer repeated bleeding events, which can cause chronic joint disease and sometimes leads to death due to the inability for blood to clot efficiently. This chronic joint disease can have significant physical, psychosocial, and quality-of-life effects, including financial burden. The current treatment is intravenous infusion of FIX protein products, either prophylactically or in response to bleeding.

The approach being tested in this study uses a novel recombinant adeno-associated virus (AAV), which in nature causes no disease, to deliver the human factor IX (hFIX) gene to the liver cells where FIX is normally made. Recent data of a gene therapy study showed preliminary encouraging results with the approach of using an AAV vector carrying the factor IX gene. This study will seek to determine the safety and kinetics of a single IV infusion of SPK-9001 (a novel AAV vector carrying a high specific activity factor IX variant).

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	15 participants
Intervention Model:	Sequential Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	GENE THERAPY, OPEN-LABEL, DOSE-ESCALATION STUDY OF SPK-9001 [ADENO-ASSOCIATED VIRAL VECTOR WITH HUMAN FACTOR IX GENE] IN SUBJECTS WITH HEMOPHILIA B
Actual Study Start Date :	November 18, 2015
Estimated Primary Completion Date :	April 2, 2019
Estimated Study Completion Date :	April 2, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: SPK-9001; Single intravenous (i.v.) infusion of SPK-9001 [an adeno-associated viral (AAV) vector with human factor IX gene] Intervention: Gene Therapy / Gene Transfer	Biological: SPK-9001; A novel, bioengineered adeno-associated viral vector carrying human factor IX variant

Outcome Measures

Primary Outcome Measures :

1. Number of participants experiencing drug-related adverse events [ Time Frame: 1 year ]
   As assessed by physical exam, vital signs, standard clinical labs, and Bethesda assay for FIX inhibitor

Secondary Outcome Measures :

1. Changes from baseline in circulating FIX activity (IU/dL or % normal) [ Time Frame: 1 Year ]
   FIX activity

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Male
Gender Based Eligibility:	Yes
Gender Eligibility Description:	Genetic Males
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Able to provide informed consent and comply with requirements of the study
• Males ≥18 y.o. with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous factor IX)
• Received ≥50 exposure days to factor IX products
• A minimum average of 4 bleeding events per year requiring episodic treatment of factor IX infusions or prophylactic factor IX infusions
• No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein
• Agree to use reliable barrier contraception until 3 consecutive samples are negative for vector sequences

Exclusion Criteria:

• Evidence of active hepatitis B or C
• Currently on antiviral therapy for hepatitis B or C
• Have significant underlying liver disease
• Have serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (* subjects who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll)
• Have detectable antibodies reactive with AAV-Spark100
• Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational drug within the last 12 weeks
• Unable or unwilling to comply with study assessments

Contacts and Locations

Locations

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United States, California
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
UC Davis CTSC Clinical Research Center
Sacramento, California, United States, 95817
UC Davis Investigational Pharmacy
Sacramento, California, United States, 95817
UC Davis Medical Center
Sacramento, California, United States, 95817
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
Mississippi Center for Advanced Medicine
Madison, Mississippi, United States, 39110
United States, New York
Weill Cornell Medicine - New York Presbyterian Hospital
New York, New York, United States, 10065
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050

Sponsors and Collaborators

Pfizer

Investigators

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Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J, Cuker A, Sullivan LM, Majumdar S, Teitel J, McGuinn CE, Ragni MV, Luk AY, Hui D, Wright JF, Chen Y, Liu Y, Wachtel K, Winters A, Tiefenbacher S, Arruda VR, van der Loo JCM, Zelenaia O, Takefman D, Carr ME, Couto LB, Anguela XM, High KA. Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant. N Engl J Med. 2017 Dec 7;377(23):2215-2227. doi: 10.1056/NEJMoa1708538.

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Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT02484092 History of Changes
Other Study ID Numbers:	C0371005; SPK-9001-101 ( Other Identifier: Alias Study Number )
First Posted:	June 29, 2015
Last Update Posted:	February 6, 2019
Last Verified:	February 2019
Individual Participant Data (IPD) Sharing Statement:
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/data_requests.
URL:	https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Pfizer:

Hemophilia B; Blood Coagulation Disorders; Gene Therapy; Gene Transfer; Factor IX Deficiency	Factor IX Gene; Factor IX Protein; Vector; AAV

Additional relevant MeSH terms:

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Hemophilia A; Hemophilia B; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases	Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked