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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02484092




Registration number
NCT02484092
Ethics application status
Date submitted
18/06/2015
Date registered
29/06/2015
Date last updated
16/06/2020

Titles & IDs
Public title
A Gene Therapy Study for Hemophilia B
Scientific 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
Secondary ID [1] 0 0
SPK-9001-101
Secondary ID [2] 0 0
C0371005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia B 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: Other - SPK-9001

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


Treatment: Other: SPK-9001
A novel, bioengineered adeno-associated viral vector carrying human factor IX variant
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings
Assessment method [1] 0 0
Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.
Timepoint [1] 0 0
Baseline up to Week 52
Primary outcome [2] 0 0
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Assessment method [2] 0 0
Vital signs (temperature, respiratory rate, pulse rate, height, weight, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs was determined at the investigator's discretion.
Timepoint [2] 0 0
Baseline up to Week 52
Primary outcome [3] 0 0
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAE
Assessment method [3] 0 0
Following parameters were analyzed for laboratory examination: hematology (neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell \[RBC\] count, hemoglobin, hematocrit, platelet count); liver function (albumin, total bilirubin, total protein, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, GGT); Lipid panel (HDL, VLDL, triglycerides, total cholesterol); clinical chemistry (sodium, potassium, chloride, bicarbonate, glucose, phosphate, serum creatinine, BUN); urinalysis (specific gravity, pH, glucose, protein, blood, ketones; coagulation, immunology, etc. Investigators determined which laboratory abnormalities were reported as treatment-emergent adverse events (TEAEs).
Timepoint [3] 0 0
Baseline up to Week 52
Primary outcome [4] 0 0
Number of Participants With Drug -Related TEAEs and Serious Adverse Events (SAEs)
Assessment method [4] 0 0
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. An AE was regarded as TEAE if the start date was on or after the infusion of SPK-9001 but before participant's last visit on study (or the date of withdrawal/the date of being lost to follow-up). Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.
Timepoint [4] 0 0
Baseline up to Week 52
Primary outcome [5] 0 0
Number of Participants With Positive Immune Reponses Against Adeno-associated Virus Vector (AAV) Capsid
Assessment method [5] 0 0
Peripheral blood mononuclear cells (PBMC) results by interferon gamma enzyme-linked immunospot assay (ELISPOT) to assess cellular immune responses to AAV capsid and to FIX were presented. The ELISPOT is a type of assay that focuses on quantitatively measuring the frequency of cytokine secretion for a single cell. The positive ELISPOT results suggested a T-cell reaction to capsid protein.
Timepoint [5] 0 0
Baseline up to Week 52
Primary outcome [6] 0 0
Number of Participants Who Reached > 150% Vector-derived FIX:C Activity Level After SPK-9001 Infusion
Assessment method [6] 0 0
Based on non-clinical studies in non-human primates (NHPs), it was not predicted that vector-derived FIX:C activity levels \>150% of normal would be achieved in this study. However, thrombin antithrombin (TAT) levels as thrombotic potential were to be measured if vector derived FIX:C activity levels \>150% of normal were achieved in any participant during the study. Blood samples for TAT at Day 0 visit (prior to FIX protein product infusion) were used to establish baseline value.
Timepoint [6] 0 0
Baseline up to Week 52
Primary outcome [7] 0 0
Number of Participants With FIX Inhibitor
Assessment method [7] 0 0
FIX inhibitors were measured using the Bethesda assay from the central and local laboratory. The Bethesda assay measures the amount of factor (FIX) inactivated when the plasma from the patient is incubated with an external source of factor for 2 hours at 37ºC. Inhibitor levels are quantified in Bethesda units (BU). An inhibitor titer of = 0.6 BU/ml is to be taken as clinically significant.
Timepoint [7] 0 0
Baseline up to Week 52
Primary outcome [8] 0 0
Incremental Recovery of FIX Product
Assessment method [8] 0 0
Incremental recovery was determined as the peak factor level recorded within the first 3 hours after infusion and was reported as (IU/ml)/(IU/kg), using the formula:(\[Activity IU/mL peak post infusion\] - \[Activity IU/mL pre-infusion\]) / (IU/kg infused).
Timepoint [8] 0 0
Day 0 and Week 52
Secondary outcome [1] 0 0
FIX:C Activity
Assessment method [1] 0 0
All samples collected from participants for plasma FIX activity levels were analyzed and used to determine peak and steady-state vector-derived circulating FIX activity levels. The vector-derived endogenous (not affected by intercurrent FIX product infusions) FIX:C activity levels were characterized by post-treatment population mean. Dose escalation and dose level expansion strategies were employed in the study based on vector-derived FIX activity levels as well as any immune responses against AAV capsid. Steady-state levels were based on 2 separate vector-derived FIX:C activity level measurements (at least 2 weeks apart) starting from Week 8-12 with adequate washout.
Timepoint [1] 0 0
Baseline up to Week 52
Secondary outcome [2] 0 0
Change From Baseline in FIX:C Antigen Level at Steady State
Assessment method [2] 0 0
The vector-derived endogenous (not affected by intercurrent FIX product infusions) FIX:C activity antigen levels were characterized by post-treatment population mean.
Timepoint [2] 0 0
Week 12 up to Week 52

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
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
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/04/2019
Sample size
Target
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown/Sydney
Recruitment postcode(s) [1] 0 0
2050 - Camperdown/Sydney
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
Mississippi
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
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
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02484092