Sickle Cell DiseasePhase 1RAISENCT03997760
A Study of SHP655 (rADAMTS13) in Sickle Cell Disease
A Phase 1 study testing TAK-755 in people with Sickle Cell Disease, run by Shire at 14 sites in United States.
Trial summary
TAK-755 (previously known as SHP655) is a medicine used to treat sickle cell disease (SCD). The main aim of the study is to measure the safety and tolerability of TAK-755 in SCD participants. Study participants will receive TAK-755 or placebo on Day 1. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- TAK-755
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 14 sitesUnited States
- Study dates
- 21 Oct 2019to 26 Oct 2022
- Phase
- Phase 1
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years at the time of signing the informed consent.
- An understanding, ability, and willingness to fully comply with study procedures and requirements.
- Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent to participate in the study.
- Male or female with a documented history of HbSS or HbSβo thalassemia (based on clinical record of genetic, electrophoresis, or high-performance liquid chromatography testing).
- Participant currently taking hydroxyurea must be on a stable dosing for 3 months at screening.
Who cannot join
- The participant was diagnosed with acute VOC in the 21 days before dosing on Day 1.
- The participant has undergone blood transfusion within the last 30 days or blood transfusion on greater than or equal to (>=) 2 occasions in the last 90 days, at Screening Visit.
- The participant has a history of acquired or congenital thrombotic thrombocytopenic purpura.
- The participant has serum creatinine level greater than (>) 1.2 milligrams per deciliter (mg/dL).
- The participant has alanine transaminase >3* upper limit of normal (based on clinical laboratory normal range), direct bilirubin level >2 mg/dL, or indirect bilirubin level >5 mg/dL at the Screening Visit.
- The participant has a hemoglobin level <5 grams per deciliter (g/dL) at the Screening Visit.
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- The participant has a platelet count of <100 000/cubic millimeter (mm^3) at the Screening Visit.
- Signs or symptoms of infection requiring treatment with IV antibiotics during the Screening Period.
- The participant has fever with body temperature of >=38.5 degree Celsius (ºC) (101.3 degree Fahrenheit [ºF]) at the Screening Visit or before dosing on Day 1.
- The participant has Acute Chest Syndrome (ACS), diagnosed or strongly suspected, as evidenced by a new infiltrate on chest radiograph, and one or more of the following criteria:
- Fever with body temperature >39°C (102.2°F)
- Hypoxia (confirmed by arterial blood gases with partial pressure of arterial oxygen (PaO2) <70 millimeter of mercury [mmHg])
- Chest pain
- Suspicious findings on physical examination (tachypnea, intercostal retraction, wheezing, and/or rales)
- The participant has recently (within the past 28 days, from Screening Visit) undergone major surgery, requires hospitalization, documented serious bacterial infection requiring antibiotic treatment, or significant bleeding.
- The participant has had a recent (within the past 90 days, from Screening Visit) episode of stroke, transient ischemic attack, symptomatic pulmonary hypertension, or seizure.
- Any history of hemorrhagic stroke or bleeding diathesis.
- The participant has received any of the following protocol-restricted medicines: a) systemic steroid therapy within 48 hours before dosing, or there is the expectation that such therapy may be given during the study (inhaled or topical steroids are allowed); b) Anticoagulant or antiplatelet therapy within the past 3 weeks before dosing; c) crizanlizumab within the past 30 days before dosing; d) voxelotor within the past 14 days before dosing.
- For participants receiving chronic or long-acting opioids, a change in dose or pain requiring medical attention in the past 14 days before dosing.
- The participant has a medical or psychiatric condition that, in the opinion of the investigator, may pose a risk to the participant for participation or interfere with the conduct or results of the study.
- The participant has received or plans to receive any other investigational agent within the 4 weeks prior to the study screening visit or during the course of the study.
- There is the expectation that the participant will not be able to be followed for the duration of the study.
- The participant is pregnant or lactating or a female of childbearing potential or male unable or unwilling to comply with birth control methods or abstinence until the end of study visit.
- The participant with active use of illicit drugs (excluding marijuana) and/or alcohol dependence, as determined by the investigator.
- The participant has been administered SHP655 previously.
- Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of SHP655.
- The participant has a positive test result for hepatitis B surface antigen, or hepatitis C antibody, or human immunodeficiency virus (HIV) antigen/antibody, at the Screening Visit. However, a participant with a hepatitis C antibody and a negative hepatitis C virus ribonucleic acid (RNA) polymerase chain reaction test is not excluded.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of Colorado Sickle Cell Treatment and Research Center
Aurora, Colorado, 80045
Johns Hopkins University School Of Medicine
Baltimore, Maryland, 21218
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
Levine Cancer Institute
Charlotte, North Carolina, 28204
University of Illinois
Chicago, Illinois, 60612-4325
Ohio State University Medical Center
Columbus, Ohio, 43210
Sickle Cell Center
Denver, Colorado, 80262
Duke University Medical Center
Durham, North Carolina, 27705
East Carolina University
Greenville, North Carolina, 27858
Arkansas Children's Hospital
Little Rock, Arkansas, 77202
University of Tennessee -- Memphis
Memphis, Tennessee, 38163-2116
Ochsner Health System
New Orleans, Louisiana, 70121
VCU Health - Research Parent
Richmond, Virginia, 23298
About this study
Official title: A Phase 1 Randomized, Double-blind, Placebo-controlled, Multicenter, Ascending Dose, Safety and PK/PD Study of SHP655 (rADAMTS13) in Sickle Cell Disease at Baseline Health
TAK-755 (previously known as SHP655) is a medicine used to treat sickle cell disease (SCD). The main aim of the study is to measure the safety and tolerability of TAK-755 in SCD participants.
Study participants will receive TAK-755 or placebo on Day 1. Their SCD will be treated by their doctor according to their doctor's usual clinical practice.
During the study, participants will be asked to follow-up on 13 days following SHP655 or placebo administration for safety assessment. Maximum duration of participation is expected to be about 2 months.
- Conditions
- Sickle Cell Disease
- Being tested
- TAK-755, Placebo
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-755Drug
Also called recombinant ADAMTS13, BAX 930, SHP655
Participants will receive TAK-755 as a single IV infusion at one of the 3 dose levels of 40 IU/kg, 80 IU/kg, or 160 IU/kg.
PlaceboOther
Participants will receive placebo matched to TAK-755 of the 3 dose levels of 40 IU/kg, 80 IU/kg, and 160 IU/kg as single IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| TAK-755 | Experimental | Participants with SCD at their baseline health will receive a single intravenous (IV) infusion at one of the 3 dose levels of 40, 80 and 160 International units per kilogram (IU/kg) in a dose escalation manner. Receives: Drug: TAK-755 |
| Placebo | Placebo comparator | Participants with SCD at their baseline health will receive placebo matched to TAK-755 of the 3 dose levels of 40 IU/kg, 80 IU/kg, and 160 IU/kg as single IV infusion. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product (IP) or medicinal product. TEAEs were defined as AEs that started or worsened in severity on or after the infusion of IP. A serious TEAEs was any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which resulted in death, was life-threatening, required inpatient hospitalization, prolongation of hospitalization, was an important medical event. TEAEs included both serious and non-serious AEs.
Measured: From date of signing informed consent up to end of study visit (Day 28)
Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755
Measurement of Anti-ADAMTS13 antibodies can be used to assess whether the body's immune system has been stimulated to react to TAK-755. Binding Anti-ADAMTS13 antibodies measure antibodies that are able to bind to ADAMTS13, whether or not the antibodies have an effect on how well ADAMTS13 works. An inhibitory Anti-ADAMTS13 antibody is antibody that both binds to ADAMTS13 and able to affect how well ADAMTS13 works. Binding and Inhibitory anti-ADAMTS13 antibodies were categorized as pre-existing, treatment-induced, and treatment-boosted. Pre-existing: anti-ADAMTS13 antibodies were detected in the baseline sample prior to infusion with TAK-755. Treatment-induced: no anti-ADAMTS13 antibodies were detected in baseline sample but were detected in any sample drawn after TAK-755 infusion. Treatment-boosted: anti-ADAMTS13 antibodies were pre-existing and were detected at any time after TAK-755 infusion at titers that were at least 4 steps higher than the titers detected before TAK-755 infusion.
Measured: From date of signing informed consent up to end of study visit (Day 28)
Secondary outcomes (16)
Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
IR was defined as the ratio of maximum increase in plasma ADAMTS13 antigen or activity level to TAK-755 dose per body weight. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. Here "IU/mL/IU/kg" refers to "International units per milliliter per international units per kilogram".
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Cmax was a measure of the maximum amount of drug in the plasma after the dose was given. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Tmax was a measure of the time to reach the maximum concentration in the plasma after the drug dose. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
t1/2 was the time required for a given drug concentration in the plasma to decrease by 50%. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
The MRT is the average time that the study product stays in the body (or plasma). The MRT0-Inf is defined as the average time from zero (pre-dose) extrapolated to infinite time (MRT0-inf). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Mean Residence Time From Zero to 72 Hours Post-dose (MRT0-72) of ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
The MRT is the average time that the study product stays in the body (or plasma) and The MRT0-72 is defined as the average time from zero (predose) to 72 hours post-dose (MRT0-72). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-Last was an area under the concentration-time curve from zero (pre-dose) to time of last quantifiable concentration. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-72 was an area under the concentration-time curve from zero (predose) to 72 hours post-dose (AUC0-72). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-inf was area under the concentration-time curve from zero (pre-dose) extrapolated to infinite time. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by MRT(0-inf)*CL. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints
Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together to stop bleeding within the body. VWF:Ag measures the level of von Willebrand factor protein in the blood. The change from baseline in VWF:Ag concentration was measured at different time points. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints
Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together, to stop bleeding within the body. VWF:RCo assay is a test that measures the activity of the VWF in a plasma sample in terms of how well it is able to clump platelets together in the presence of the antibiotic ristocetin. Change from baseline in vWF:RCo concentration was measured at different timepoints. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Measured: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Platelet Count at Specified Timepoints
Blood samples were collected to analyze platelet count. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Thechange from baseline was calculated by subtracting the baseline value from the post-dose value.
Measured: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints
The plasma free hemoglobin test measures the level of hemoglobin in the plasma (that is, not contained within the red blood cells). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Measured: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints
Change from baseline in plasma thrombospondin levels over time was reported. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Measured: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 288, and 648 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2019
- Study start21 Oct 2019
- Primary completion26 Oct 2022
- Study completion26 Oct 2022
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 Sickle Cell DiseaseStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03997760
- Sponsor's protocol ID
- SHP655-101
- Acronym
- RAISE
- Status last verified
- Apr 2024
- First submitted
- 14 Jun 2019
- Last updated
- 23 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Randomized, Double-blind, Placebo-controlled, Multicenter, Ascending Dose, Safety and PK/PD Study of SHP655 (rADAMTS13) in Sickle Cell Disease at Baseline Health
- ClinicalTrials.gov ID
- NCT03997760
- Acronym / sponsor ID
- RAISE / SHP655-101
- Conditions
- Sickle Cell Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 21 Oct 2019 (actual)
- Primary completion
- 26 Oct 2022 (actual)
- Study completion
- 26 Oct 2022 (actual)
- First posted
- 25 Jun 2019 (actual)
- Results
- Posted 23 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
TAK-755 (previously known as SHP655) is a medicine used to treat sickle cell disease (SCD). The main aim of the study is to measure the safety and tolerability of TAK-755 in SCD participants.
Study participants will receive TAK-755 or placebo on Day 1. Their SCD will be treated by their doctor according to their doctor's usual clinical practice.
During the study, participants will be asked to follow-up on 13 days following SHP655 or placebo administration for safety assessment. Maximum duration of participation is expected to be about 2 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAK-755 | Experimental | Drug: TAK-755Participants with SCD at their baseline health will receive a single intravenous (IV) infusion at one of the 3 dose levels of 40, 80 and 160 International units per kilogram (IU/kg) in a dose escalation manner. |
| Placebo | Placebo comparator | Other: PlaceboParticipants with SCD at their baseline health will receive placebo matched to TAK-755 of the 3 dose levels of 40 IU/kg, 80 IU/kg, and 160 IU/kg as single IV infusion. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 to 65 years at the time of signing the informed consent.
- An understanding, ability, and willingness to fully comply with study procedures and requirements.
- Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent to participate in the study.
- Male or female with a documented history of HbSS or HbSβo thalassemia (based on clinical record of genetic, electrophoresis, or high-performance liquid chromatography testing).
- Participant currently taking hydroxyurea must be on a stable dosing for 3 months at screening.
Key exclusion criteria (27 listed)
- The participant was diagnosed with acute VOC in the 21 days before dosing on Day 1.
- The participant has undergone blood transfusion within the last 30 days or blood transfusion on greater than or equal to (>=) 2 occasions in the last 90 days, at Screening Visit.
- The participant has a history of acquired or congenital thrombotic thrombocytopenic purpura.
- The participant has serum creatinine level greater than (>) 1.2 milligrams per deciliter (mg/dL).
- The participant has alanine transaminase >3* upper limit of normal (based on clinical laboratory normal range), direct bilirubin level >2 mg/dL, or indirect bilirubin level >5 mg/dL at the Screening Visit.
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 |
|---|---|---|
| TAK-755Also: recombinant ADAMTS13, BAX 930, SHP655Participants will receive TAK-755 as a single IV infusion at one of the 3 dose levels of 40 IU/kg, 80 IU/kg, or 160 IU/kg. | Drug | TAK-755 |
| PlaceboParticipants will receive placebo matched to TAK-755 of the 3 dose levels of 40 IU/kg, 80 IU/kg, and 160 IU/kg as single IV infusion. | Other | Placebo |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs)
Time frame: From date of signing informed consent up to end of study visit (Day 28)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product (IP) or medicinal product. TEAEs were defined as AEs that started or worsened in severity on or after the infusion of IP. A serious TEAEs was any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which resulted in death, was life-threatening, required inpatient hospitalization, prolongation of hospitalization, was an important medical event. TEAEs included both serious and non-serious AEs.
Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755
Time frame: From date of signing informed consent up to end of study visit (Day 28)
Measurement of Anti-ADAMTS13 antibodies can be used to assess whether the body's immune system has been stimulated to react to TAK-755. Binding Anti-ADAMTS13 antibodies measure antibodies that are able to bind to ADAMTS13, whether or not the antibodies have an effect on how well ADAMTS13 works. An inhibitory Anti-ADAMTS13 antibody is antibody that both binds to ADAMTS13 and able to affect how well ADAMTS13 works. Binding and Inhibitory anti-ADAMTS13 antibodies were categorized as pre-existing, treatment-induced, and treatment-boosted. Pre-existing: anti-ADAMTS13 antibodies were detected in the baseline sample prior to infusion with TAK-755. Treatment-induced: no anti-ADAMTS13 antibodies were detected in baseline sample but were detected in any sample drawn after TAK-755 infusion. Treatment-boosted: anti-ADAMTS13 antibodies were pre-existing and were detected at any time after TAK-755 infusion at titers that were at least 4 steps higher than the titers detected before TAK-755 infusion.
16 secondary outcomes
Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Mean Residence Time From Zero to 72 Hours Post-dose (MRT0-72) of ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Platelet Count at Specified Timepoints
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 288, and 648 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2024.
- 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: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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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
Takeda
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAK-755 in people with Sickle Cell Disease, run by Shire at 14 sites in United States.
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 27 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: finished, as of the sponsor's last update on 23 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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 23 Apr 2024). 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 Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) (time frame: From date of signing informed consent up to end of study visit (Day 28)). The study lists 2 primary outcomes in all. 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 23 Apr 2024.