Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B

Pfizer

Status and phase: Active, not recruiting; Phase 2

Conditions: Hemophilia B

Treatments: Biological: PF-06838435 (formerly SPK-9001)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03307980

C0371003

SPK-9001-LTFU-101 (Other Identifier)

Details and patient eligibility

About

Long-term safety and efficacy follow-up for participants with Hemophilia B who were previously treated in the C0371005 (formerly SPK-9001-101) study, and a dose-escalation sub-study evaluating safety, tolerability, and kinetics of a higher dose with long-term safety and efficacy follow-up. Participants in the substudy do not need to have participated in C0371005.

Full description

Evaluation of the long-term level of persistence and potential late or delayed adverse events associated with PF-06838435 (formerly SPK-9001), assessment of the durability of the transgene expression, and determination of the effects of PF-06838435 on clinical outcomes in individuals who have previously received a single administration of PF-06838435 in the C0371005 study. Amendment 2 of this study incorporates a dose-escalation substudy to evaluate the safety, tolerability, and kinetics of a single IV infusion of PF-06838435 at a higher dose than that used in the C0371005 study. The dose-escalation participants will also be followed for long-term safety and efficacy.

Enrollment: 21 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

This study is currently only enrolling into the dose-escalation substudy with subsequent long-term follow-up. The Eligibility Criteria for entry into the dose-escalation substudy is presented below:

Inclusion Criteria:

1. Able to provide informed consent and comply with requirements of the study
2. Males age 18 to 65 years with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous factor IX)
3. Received ≥50 exposure days to factor IX products
4. No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein
5. Agree to refrain from donating sperm and either abstain from intercourse or use reliable barrier contraception until 3 consecutive semen samples are negative for vector sequences

Exclusion Criteria:

1. Evidence of active hepatitis B or C
2. Currently on antiviral therapy for hepatitis B or C
3. Have significant underlying liver disease
4. Serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (* participants who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll)
5. Neutralizing antibody titers to the capsid portion of PF-06838435 above the established threshold
6. Sensitivity to heparin or heparin induced thrombocytopenia; sensitivity to any of the study interventions, or components thereof, or drug or other allergy
7. Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 3 months of screening visit
8. Any concurrent clinically significant major disease or condition
9. Unable or unwilling to comply with the study procedures

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 1 patient group

PF-06838435 Dose-Escalation

Experimental group

Description:

Single intravaneous infusion of PF-06838435. After 2 participants receive initial dose, data will be evaluated and a decision will be made to escalate or reduce the dose being evaluated, increase the number of participants receiving the dose, or stop dosing. Multiple iterations may be undertaken.

Treatment:

Biological: PF-06838435 (formerly SPK-9001)