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Also known as rADAMTS-13, TAK-755, recombinant ADAMTS13, BAX 930
SHP655 · 7 trials · 5 indications
TEAE: any adverse event emerging or manifesting at or after the initiation of treatment with TAK-755 or any existing adverse event that worsens in either intensity or frequency following exposure to TAK-755. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
The Heidelberg Bleeding Classification System is used to determine whether an Intracranial Hemorrhage (ICH) is symptomatic (sICH) or asymptomatic (aICH). It uses a structured 7-step approach that integrates imaging findings with clinical deterioration. This algorithm includes anatomic description of hemorrhage, adjudication of neurological deterioration, and relatedness between ICH and clinical deterioration. Percentage of participants who develop sICH will be reported.
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event. Adverse events of special interest include major thrombotic events and treatment-related bleeding events.
ADAMTS-13 Activity Levels was assessed by fluorescence resonance energy transfer (FRETS) ADAMTS13 activity, with or without SHP655 Supplementation. Schedule A (Days 1, 2, 3, 4, 6, 8, 11, and every 3 days thereafter) or Schedule B (Days 1, 2, 3, 5, 7, 9, 12, and every 3 days thereafter). Data is reported for multiple timepoints as Within 15 minutes pre-PEX and post-PEX; Within 15 minutes, 0.5-3 hours, 4-6 hours post end of investigational product (IP) infusion 1; Within 15 minutes, 0.5-3 hours post end IP infusion 2; 30 minutes pre-IP infusion 2 of Schedule A and Schedule B (up to Day 11 or 12).
The platelet counts are reported in units of 10\^9 per liter blood.
The lactate dehydrogenase levels are reported.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Prophylactic Cohort: TAK-755 | EXPERIMENTAL | All participants will receive prophylactic treatment with 40 IU/kg TAK-755 intravenous (IV) infusions once every week or once every other week for the duration of the study. Participants who are naïve will receive an initial IV dose of 40 IU/kg TAK-755 to allow measurement of the pharmacokinetics of TAK-755, followed by prophylactic treatment with 40 IU/kg TAK-755 by IV infusion once every week or once every other week for the duration of the study. |
| On-Demand Cohort: TAK-755 | EXPERIMENTAL | Participants will receive daily IV infusions of TAK-755 when experiencing an acute thrombotic thrombocytopenic purpura (TTP) event until 2 days after the acute TTP event is resolved. Participants will receive 40 IU/kg TAK-755 on the first day, followed by 20 IU/kg on Day 2, and then 15 IU/kg daily until 2 days after the acute TTP event has resolved. Upon resolution of the acute TTP event, participants may choose to move to the prophylactic cohort of the study or discontinue entirely from the study. |
| Prophylaxis Cohort I: TAK-755 Then SoC | EXPERIMENTAL | Participants received a single intravenous (IV) infusion of 40 international units per kilogram (IU/kg) rADAMTS13 manufactured in Orth, Austria (TAK-755 ORT), every 2 weeks (Q2W) for 6 months in Period 1 followed by standard of care (SoC) for 6 months in Period 2. Thereafter participants received rADAMTS13 manufactured in Singapore (TAK-755 SIN), dose IV infusion of 40 IU/kg Q2W for 6 months in Period 3. TAK-755 ORT could be replaced with TAK-755 SIN and vice versa depending on availability and other criteria. |
| Prophylaxis Cohort II: SoC Then TAK-755 | EXPERIMENTAL | Participants received SoC for 6 months in Period 1 followed by IV infusions of 40 IU/kg dose of TAK-755 ORT Q2W in Period 2 for the next 6 months. Thereafter participants received TAK-755 SIN dose IV infusions of 40 IU/kg Q2W for another 6 months in Period 3. TAK-755 ORT could be replaced with TAK-755 SIN and vice versa depending on availability and other criteria. |
| On Demand Cohort I: TAK-755 | EXPERIMENTAL | Participants experiencing an acute TTP event who met all other inclusion criteria and entered the study through the TAK-755 cohort of the Urgent Treatment Period received initial dose of IV infusion 40 IU/kg \[+/- 4 IU/kg\] TAK-755 ORT or TAK-755 SIN on Day 1 followed by a subsequent dose IV infusions of 20 IU/kg \[+/- 2 IU/kg\] TAK-755 ORT or TAK-755 SIN on Day 2 and an additional daily dose IV infusions of 15 IU/kg \[+/- 1.5 IU/kg\] TAK-755 on Day 3 until 2 days after the acute event was resolved. Upon resolution of the acute TTP event, participants had the option to either move to the prophylaxis cohort of the study or discontinue entirely. |
| On Demand Cohort II: SoC | EXPERIMENTAL | Participants experiencing an acute TTP event who met all other inclusion criteria and entered the study through the SoC cohort of the Urgent Treatment Period received the investigator-recommended SoC and dosing regimen until the acute event was resolved. Upon resolution of the acute TTP event, participants had the option to either move to the prophylaxis cohort of the study or discontinue entirely. |
| Part A: TAK-755 | EXPERIMENTAL | Participants will receive a single intravenous (IV) infusion of TAK-755 on Day 1 of Part A. All participants will be followed for up to 90 days post treatment. |
| Part B: TAK-755 | EXPERIMENTAL | Participants will receive a single IV infusion of TAK-755 on Day 1 of Part B. All participants will be followed for up to 90 days post treatment. |
| Part A and B: Placebo | PLACEBO_COMPARATOR | Participants will receive a single IV infusion of TAK-755 matching placebo on Day 1 of Parts A and B. All participants will be followed for up to 90 days post treatment. |
| Part 1: TAK-755 Dose 1 in Acute Phase and Dose 2 in Post-acute Phase | EXPERIMENTAL | TAK-755 Dose 1, IV infusion, in the acute phase until clinical response is achieved. All participants achieving clinical response will receive TAK-755 at Dose 2, for up to 6 weeks during the post-acute phase. |
| Part 1: TAK-755 Dose 2 in Both Acute and Post-Acute Phase | EXPERIMENTAL | TAK-755 Dose 2, IV infusion, in the acute phase until clinical response is achieved. All participants achieving clinical response will receive TAK-755 at Dose 2, for up to 6 weeks during the post-acute phase. |
| Part 2: TAK-755 Dose 3 in Acute Phase and Dose 2 in Post-acute Phase | EXPERIMENTAL | TAK-755 Dose 3, IV infusion, in the acute phase until 48-hour platelet response is achieved. All participants achieving platelet response will receive TAK-755 at Dose 2, 4 times per week for Week 1 and 3 times per week for Week 2 and 3 during the post-acute phase based on investigator judgement as high-risk for developing iTTP recurrence. |
| Standard of Care (SoC) + Placebo | PLACEBO_COMPARATOR | Participants received SoC daily PEX followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months). |
| SoC + SHP655 + Placebo | EXPERIMENTAL | Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months). |
| SoC + SHP655 | EXPERIMENTAL | Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months). |
| 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. |
| 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. |
| Recombinant ADAMTS13 | EXPERIMENTAL | The study is comprised of 3 dose cohorts and two dose escalation steps \[Cohort 1: 3 subjects; Cohort 2: 3 subjects; Cohort 3: 8 subjects\]. Subjects will be enrolled and dosed sequentially. Subjects will be recruited to the next dose level only after short-term safety has been demonstrated and reviewed by an independent Data Monitoring Committee (DMC) at the preceding dose level. The first 2 subjects in any cohort will be ≥ 18 years of age. The effects of the investigational product on vital signs, hematology, and clinical chemistry parameters (up to 96 ± 2 hrs blood sampling timepoint) will determine short-term safety. The DMC will recommend whether to proceed with the study or in case of a safety concern recommend remedial actions and/or to discontinue the study. Subject participation will continue until 28 ± 3 days after infusion of the investigational product. Subject participation in one Dose Cohort (1-3) is expected to be approximately 6-8 weeks. |
| Name | Type | Description |
|---|---|---|
| TAK-755 | BIOLOGICAL | TAK-755 IV infusion |
| Standard of care | BIOLOGICAL | Participants will receive Investigator-recommended Standard of care (SoC). |
| Placebo | OTHER | TAK-755 matching placebo IV infusion. |
| SHP655 | DRUG | Participants will receive injection of SHP655. |
| Recombinant ADAMTS13 | DRUG | rADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is a lyophilized formulation for intravenous injection. The lyophilized rADAMTS13 is reconstituted with sterile water for injection. Subjects will receive an intravenous injection with rADAMTS13 at a dose of either 5 U/kg bodyweight (Cohort 1), or 20 U/kg bodyweight (Cohort 2), or 40 U/kg bodyweight (Cohort 3). |
Inclusion Criteria: Participants who have completed TAK-755 Phase 3 pivotal Study 281102 (NCT03393975) in the prophylactic cohort and who meet all of the following criteria are eligible for this study: * Participants or legally authorized representative has provided signed informed consent \>=18 y...
SHP655 is an investigational small molecule being studied for the treatment of Acquired Thrombotic Thrombocytopenic Purpura (aTTP), a rare blood disorder. It is currently in Phase 2 clinical development and has not been approved by regulatory authorities.
SHP655 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The drug is an investigational small molecule in Phase 2 clinical development for Acquired Thrombotic Thrombocytopenic Purpura (aTTP).
SHP655 is in Phase 2 clinical development. It is an investigational drug for Acquired Thrombotic Thrombocytopenic Purpura (aTTP) and has not been approved by regulatory authorities. One Phase 2 trial has been completed.
SHP655 has one completed Phase 2 clinical trial, NCT03922308, titled "Study of rADAMTS-13 (SHP655) in the Treatment of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)." The trial enrolled 28 participants across the United States, Canada, France, Germany, Italy, Spain, and the United Kingdom.
Yes, SHP655 is also known as rADAMTS-13. The clinical trial NCT03922308 refers to the drug as rADAMTS-13 (SHP655) in its title, confirming that both names refer to the same investigational drug for Acquired Thrombotic Thrombocytopenic Purpura (aTTP).