Study Stopped
Takeda has decided to not further develop the SHP648 (TAK-748) program. No subjects have been dosed with SHP648. The decision to terminate study SHP648-101 is not due to any safety concerns.
A Phase 1/2 Study of SHP648, an Adeno-Associated Viral Vector for Gene Transfer in Hemophilia B Subjects
An Open-Label, Multinational, Phase 1/2 Study of the Safety and Dose Escalation of SHP648, an Adeno-Associated Virus Serotype 8 (AAV8) Vector Expressing FIX Padua in Hemophilia B Subjects
2 other identifiers
interventional
2
2 countries
2
Brief Summary
The purpose of this study is to evaluate the safety and dose escalation of SHP648 an adeno-associated viral vector for gene transfer in hemophilia B participants.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2020
2 active sites
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
Study Start
First participant enrolled
May 13, 2020
CompletedFirst Submitted
Initial submission to the registry
May 15, 2020
CompletedFirst Posted
Study publicly available on registry
May 19, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 3, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 3, 2021
CompletedResults Posted
Study results publicly available
May 19, 2022
CompletedMay 19, 2022
April 1, 2022
12 months
May 15, 2020
April 27, 2022
May 17, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With SHP648 Related Serious and Non- Serious Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this investigational product (IP) or medicinal product. A Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly.
From study start date to Month 12
Secondary Outcomes (8)
Plasma Factor IX (FIX) Levels Before and After SHP648 Infusion
From study start date to Month 12
Annualized Bleed Rate (ABR) Before and After SHP648 Infusion
From study start date to Month 12
Number of Participants With Positive Binding Antibody Titers to Adeno-Associated Virus (AAV8)
From study start date to Month 12
Number of Participants With Positive Neutralizing Antibody Titers to AAV8
From study start date to Month 12
Number of Participants With T-cell Response to AAV8
From study start date to Month 12
- +3 more secondary outcomes
Study Arms (3)
Cohort 1
EXPERIMENTALCohort 1 participants will receive a single intravenous (IV) infusion of SHP648 on the day of dosing (Day 0).
Cohort 2
EXPERIMENTALCohort 2 participants will receive a single IV infusion of SHP648 at a 2 to 3-fold escalation of Cohort 1 on the day of dosing (Day 0).
Cohort 3
EXPERIMENTALCohort 3 participants will receive a single IV infusion of SHP648 at a 2 to 3-fold escalation of Cohort 2 on the day of dosing (Day 0).
Interventions
Participants will receive a single IV infusion of SHP648 in Cohort 1, 2, 3 on Day 0.
Eligibility Criteria
You may qualify if:
- Male, aged 18 to 75 years at the time of screening.
- Established severe or moderately severe hemophilia B (plasma FIX activity lesser than or equal to \[\<=\] 2 percent (%) measured following greater than or equal to \[\>=\] 5 half-lives of most recent exposure to exogenous FIX) and either \>= 3 hemorrhages per year requiring treatment with exogenous FIX or use of prophylactic therapy.
- History of greater than (\>) 50 exposure days to exogenously administered FIX concentrates or cryoprecipitates.
- Sexually active men must agree to use barrier contraception (combination of a condom and spermicide) or limit sexual intercourse to post-menopausal, surgically sterilized, or contraception-practicing partners for a minimum of 6 months after administration of SHP648, or until SHP648 genomes are no longer detected in the semen (whichever is sooner).
- Signed informed consent.
You may not qualify if:
- Bleeding disorder(s) other than hemophilia B.
- Documented laboratory evidence of having developed inhibitors (\>= 0.6 Bethesda Units \[BU\] on any single test) to FIX proteins at any time.
- Documented prior allergic reaction to any FIX product.
- Anti-AAV8 neutralizing antibody titer \>= 1:5.
- Known hypersensitivity to prednisolone or prednisone, or to any of the excipients.
- Having a disease in which treatment with prednisolone or prednisone is not tolerated (including, but not limited to osteoporosis with vertebral fractures, severe labile hypertension, and brittle diabetes).
- Evidence of markers of potential underlying risk for autoimmune mediated hepatic disease:
- Anti-smooth muscle antibody (ASMA) titer \>= 1:40. Values of 1:31 to 1:39 will be flagged as possibly abnormal and the Investigator and Medical Monitor will evaluate the participant for eligibility
- Elevated anti-liver-kidney microsomal antibody type 1 (LKM1) titers
- Total Immunoglobulin G (IgG) \> 1.5x upper limit of normal (ULN)
- Antinuclear antibody (ANA) titer \> 1:320 OR ANA titer \> 1:80 if demonstrated concurrently with alanine aminotransferase (ALT) that is \> ULN
- Active Hepatitis C: as indicated by detectable hepatitis C virus ribonucleic acid (HCV RNA) by polymerase chain reaction (PCR).
- Hepatitis B: If surface hepatitis B virus (HBV) antigen is positive.
- Receiving chronic systemic antiviral and/or interferon therapy within 4 weeks prior to enrollment.
- Clinically significant infections (e.g., systemic fungal infections) requiring systemic treatment.
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Hospital Universitario Virgen de la Arrixaca
El Palmar, 30120, Spain
Ege University Medical Faculty
Izmir, 35100, Turkey (Türkiye)
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The study was terminated by the Sponsor. Only 2 participants were screened and signed informed consent but none received any treatment during this study. No participants were evaluated, and no data was collected to be reported here, in order to protect and maintain participant's privacy/confidentiality.
Results Point of Contact
- Title
- Study Director
- Organization
- Shire
Study Officials
- STUDY DIRECTOR
Study Director
Shire
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 15, 2020
First Posted
May 19, 2020
Study Start
May 13, 2020
Primary Completion
May 3, 2021
Study Completion
May 3, 2021
Last Updated
May 19, 2022
Results First Posted
May 19, 2022
Record last verified: 2022-04
Data Sharing
- IPD Sharing
- Will not share
De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites)