Clinical trial NCT02484092: A Gene Therapy Study for Hemophilia B
Official title: Gene Therapy, Open-label, Dose-escalation Study of PF-06838435 (SPK-9001) [Adeno-associated Viral Vector With Human Factor IX Gene] in Subjects With Hemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia B
Keywords: Hemophilia B
Blood Coagulation Disorders
Gene Therapy
Gene Transfer
Factor IX Deficiency
Factor IX Gene
Factor IX Protein
Vector
AAV
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-06-29
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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).

Eligibility 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)
* Neutralizing antibodies reactive with AAV-Spark100 above and/or below a defined titre
* 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

Primary outcomes:
measure: Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings
timeFrame: Baseline up to Week 52
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to Week 52
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAE
timeFrame: Baseline up to Week 52
measure: Number of Participants With Drug -Related TEAEs and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 52
measure: Number of Participants With Positive Immune Reponses Against Adeno-associated Virus Vector (AAV) Capsid
timeFrame: Baseline up to Week 52
measure: Number of Participants Who Reached > 150% Vector-derived FIX:C Activity Level After SPK-9001 Infusion
timeFrame: Baseline up to Week 52
measure: Number of Participants With FIX Inhibitor
timeFrame: Baseline up to Week 52
measure: Incremental Recovery of FIX Product
timeFrame: Day 0 and Week 52
Secondary outcomes:
measure: FIX:C Activity
timeFrame: Baseline up to Week 52
measure: Change From Baseline in FIX:C Antigen Level at Steady State
timeFrame: Week 12 up to Week 52
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis CTSC Clinical Research Center
state: California
city: Sacramento
country: United States
facility: UC Davis Ellison Ambulatory Care Clinic
state: California
city: Sacramento
country: United States
facility: UC Davis Investigational Pharmacy
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Madison
country: United States
facility: Mississippi Center for Advanced Medicine
state: Mississippi
city: New York
country: United States
facility: Weill Cornell Medicine - New York Presbyterian Hospital
state: New York
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Camperdown/Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.