Brief Summary

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

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_2

Timeline

Completed

Started Nov 2015

Typical duration for phase_2

Geographic Reach

2 countries

10 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.4 years study duration

First Submitted

Initial submission to the registry

June 18, 2015

Completed

11 days until next milestone

First Posted

Study publicly available on registry

June 29, 2015

Completed

5 months until next milestone

Study Start

First participant enrolled

November 18, 2015

Completed

3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 8, 2019

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 8, 2019

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

May 19, 2020

Completed

Last Updated

June 16, 2020

Status Verified

June 1, 2020

Enrollment Period

3.4 years

First QC Date

June 18, 2015

Results QC Date

April 4, 2020

Last Update Submit

June 3, 2020

Conditions

Hemophilia B

Keywords

Hemophilia BBlood Coagulation DisordersGene TherapyGene TransferFactor IX DeficiencyFactor IX GeneFactor IX ProteinVectorAAV

Outcome Measures

Primary Outcomes (8)

Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings
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.
Baseline up to Week 52
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
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.
Baseline up to Week 52
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAE
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).
Baseline up to Week 52
Number of Participants With Drug -Related TEAEs and Serious Adverse Events (SAEs)
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.
Baseline up to Week 52
Number of Participants With Positive Immune Reponses Against Adeno-associated Virus Vector (AAV) Capsid
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.
Baseline up to Week 52
Number of Participants Who Reached > 150% Vector-derived FIX:C Activity Level After SPK-9001 Infusion
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.
Baseline up to Week 52
Number of Participants With FIX Inhibitor
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.
Baseline up to Week 52
Incremental Recovery of FIX Product
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).
Day 0 and Week 52

Secondary Outcomes (2)

FIX:C Activity
Baseline up to Week 52
Change From Baseline in FIX:C Antigen Level at Steady State
Week 12 up to Week 52

Study Arms (1)

SPK-9001

EXPERIMENTAL

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

Interventions

SPK-9001BIOLOGICAL

A novel, bioengineered adeno-associated viral vector carrying human factor IX variant

SPK-9001

Eligibility Criteria

Age18 Years+

Sexmale(Gender-based eligibility)

Gender Eligibility DetailsGenetic Males

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.