Hemophilia BPhase 1/2NCT04394286
A Phase 1/2 Study of SHP648, an Adeno-Associated Viral Vector for Gene Transfer in Hemophilia B Subjects
A Phase 1/2 study testing SHP648 in people with Hemophilia B, run by Baxalta now part of Shire at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- SHP648
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 13 May 2020to 3 May 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 40Show fewer
- 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.
- Known immune disorder (including myeloma and lymphoma).
- Concurrent chemotherapy or biological therapy for treatment of neoplastic disease or other disorders.
- An absolute neutrophil count lesser than < 1000 cells per cubic millimetre (cells/mm^3).
- Markers of hepatic inflammation or cirrhosis as evidenced by 1 or more of the following:
- Platelet count < 150,000/microliter (μL)
- Albumin <= 3.5 gram per deciliter (g/dL)
- Total bilirubin > 1.5x ULN and direct bilirubin >= 0.5 milligram per deciliter (mg/dL)
- ALT or Aspartate aminotransferase (AST) > 1.0x ULN
- Alkaline phosphatase > 2.0x ULN
- History of liver biopsy or imaging indicating moderate or severe fibrosis (Metavir staging of F2 or greater)
- History of ascites, varices, variceal hemorrhage, or hepatic encephalopathy
- FibroSURE Score >= 0.4
- Prothrombin time international normalized ratio (INR) >= 1.4
- Serum creatinine > 1.5 mg/dL.
- Human immunodeficiency virus (HIV) if cluster of differentiation 4 (CD4)+ cell count <= 200 mm^3 and/or viral load > 20 copies per milliliter (copies/mL).
- Urine protein > 30 mg/dL.
- Body mass index > 38.
- Orthopedic or other major surgery planned within 6 months after enrollment.
- Acute or chronic disease that, in the opinion of the Investigator, would adversely affect participant safety or compliance or interpretation of study results.
- Received an AAV vector previously or any other gene transfer agent in the previous 12 months prior to Study Day 0.
- Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease).
- History of arterial or venous thrombosis / thromboembolism, or a known pro-thrombotic condition.
- Recent history of psychiatric illness or cognitive dysfunction (including drug or alcohol abuse) that, in the opinion of the Investigator, is likely to impair participants ability to comply with protocol mandated procedures.
- Participation in another study involved with an investigational agent.
- Participant is family member or employee of the Investigator.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: 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
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.
Read the detailed description
This study will consists of 3 dose cohorts with 2-7 participants in each of the three ascending dose cohorts. Initially 2 participants will be dosed in Cohort 1, followed by dosing of up to 5 additional participants if the cohort is expanded. Participants in cohort 2 and 3 will receive 2-fold or 3-fold dose escalation to their respective preceding cohort doses if required.
- Conditions
- Hemophilia B
- Being tested
- SHP648
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHP648Genetic
Also called TAK748, AAV8.ss-3xCRM8-TTR-FIX_R338Lopt
Participants will receive a single IV infusion of SHP648 in Cohort 1, 2, 3 on Day 0.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Cohort 1 participants will receive a single intravenous (IV) infusion of SHP648 on the day of dosing (Day 0). Receives: Genetic: SHP648 |
| Cohort 2 | Experimental | Cohort 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). Receives: Genetic: SHP648 |
| Cohort 3 | Experimental | Cohort 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). Receives: Genetic: SHP648 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From study start date to Month 12
Secondary outcomes (8)
Plasma Factor IX (FIX) Levels Before and After SHP648 Infusion
Plasma FIX levels before and after SHP648 infusion were planned to be reported.
Measured: From study start date to Month 12
Annualized Bleed Rate (ABR) Before and After SHP648 Infusion
ABR was to be assessed based upon each individual bleeding episode. A bleed episode was defined as subjective (example, pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FIX. ABR before and after SHP648 administration was planned to be reported.
Measured: From study start date to Month 12
Number of Participants With Positive Binding Antibody Titers to Adeno-Associated Virus (AAV8)
Number of participants with positive binding antibodies titers to AAV8 was planned to be reported.
Measured: From study start date to Month 12
Number of Participants With Positive Neutralizing Antibody Titers to AAV8
Number of participants with positive neutralizing antibodies to AAV8 was planned to be reported.
Measured: From study start date to Month 12
Number of Participants With T-cell Response to AAV8
Number of participants with T-cell response to AAV8 was planned to be reported.
Measured: From study start date to Month 12
Number of Participants With T-cell Response to FIX Transgene Products
Number of participants with T-cell response to FIX transgene products was planned to be reported.
Measured: From study start date to Month 12
Duration of SHP648 Genomes Present in Bodily Fluids
Duration of SHP648 genomes present in bodily fluids such as serum, blood, saliva, urine, stool, and semen was planned to be reported.
Measured: From study start date to Month 12
Percent Change in Consumption of FIX Before and After Gene Transfer
Percent change in consumption of exogenous FIX before and after gene transfer was planned to be reported.
Measured: From study start date to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start13 May 2020
- Primary completion3 May 2021
- Study completion3 May 2021
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04394286
- Sponsor's protocol ID
- SHP648-101
- Other IDs
- 2018-004024-11, 2018
- Status last verified
- Apr 2022
- First submitted
- 15 May 2020
- Last updated
- 19 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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)
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04394286
- Acronym / sponsor ID
- SHP648-101
- Conditions
- Hemophilia B
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 13 May 2020 (actual)
- Primary completion
- 3 May 2021 (actual)
- Study completion
- 3 May 2021 (actual)
- First posted
- 19 May 2020 (actual)
- Results
- Posted 19 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will consists of 3 dose cohorts with 2-7 participants in each of the three ascending dose cohorts. Initially 2 participants will be dosed in Cohort 1, followed by dosing of up to 5 additional participants if the cohort is expanded. Participants in cohort 2 and 3 will receive 2-fold or 3-fold dose escalation to their respective preceding cohort doses if required.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Genetic: SHP648Cohort 1 participants will receive a single intravenous (IV) infusion of SHP648 on the day of dosing (Day 0). |
| Cohort 2 | Experimental | Genetic: SHP648Cohort 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 | Experimental | Genetic: SHP648Cohort 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (40 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SHP648Also: TAK748, AAV8.ss-3xCRM8-TTR-FIX_R338LoptParticipants will receive a single IV infusion of SHP648 in Cohort 1, 2, 3 on Day 0. | Genetic | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Number of Participants With SHP648 Related Serious and Non- Serious Adverse Events (AEs)
Time frame: From study start date to Month 12
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.
8 secondary outcomes
Plasma Factor IX (FIX) Levels Before and After SHP648 Infusion
Time frame: From study start date to Month 12
Annualized Bleed Rate (ABR) Before and After SHP648 Infusion
Time frame: From study start date to Month 12
Number of Participants With Positive Binding Antibody Titers to Adeno-Associated Virus (AAV8)
Time frame: From study start date to Month 12
Number of Participants With Positive Neutralizing Antibody Titers to AAV8
Time frame: From study start date to Month 12
Number of Participants With T-cell Response to AAV8
Time frame: From study start date to Month 12
Number of Participants With T-cell Response to FIX Transgene Products
Time frame: From study start date to Month 12
Duration of SHP648 Genomes Present in Bodily Fluids
Time frame: From study start date to Month 12
Percent Change in Consumption of FIX Before and After Gene Transfer
Time frame: From study start date to Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain more information on the study, click here/on this linkLink provided by the sponsor.
- Individual participant dataSharing planned: No. 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Shire
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SHP648 in people with Hemophilia B, run by Baxalta now part of Shire at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain, Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With SHP648 Related Serious and Non- Serious Adverse Events (AEs) (time frame: From study start date to Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2022; AzTrials last refreshed its copy on 7 Nov 2026.