A Gene Therapy Study for Hemophilia B

Browse trials for

• Hemophilia A 866
• Hemophilia B 271

Keywords

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

Hemophilia A

866 studies on the registry are indexed under Hemophilia A; 137 are open to participants now.

This study's enrollment of 15 is below the median of 28 across 512 interventional studies indexed under Hemophilia A.

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Study arms

• 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

Interventions

• BiologicalSPK-9001

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

Primary outcomes

1. 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.

   Time frame: Baseline up to Week 52

2. 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.

   Time frame: Baseline up to Week 52

3. 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).

   Time frame: Baseline up to Week 52

4. 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.

   Time frame: Baseline up to Week 52

5. 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.

   Time frame: Baseline up to Week 52

6. 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.

   Time frame: Baseline up to Week 52

7. 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.

   Time frame: Baseline up to Week 52

8. 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).

   Time frame: Day 0 and Week 52

Secondary outcomes

1. FIX:C Activity

   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.

   Time frame: Baseline up to Week 52

2. Change From Baseline in FIX:C Antigen Level at Steady State

   The vector-derived endogenous (not affected by intercurrent FIX product infusions) FIX:C activity antigen levels were characterized by post-treatment population mean.

   Time frame: Week 12 up to Week 52

Baseline characteristics

Publications

• 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. PubMed 29211678 ↗

Study documents

• Statistical analysis plan · Nov 1, 2019
• Study protocol · Jun 14, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.