Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Conditions
Brief summary
The purpose of this study is to evaluate the pharmacokinetics, safety, and efficacy of rADAMTS-13 (SHP655) administered in addition to standard of care (SoC) treatment of acquired thrombotic thrombocytopenic purpura (aTTP) participants.
Interventions
OTHERPlacebo
Participants will receive injection of placebo matched to SHP655.
DRUGSHP655
Participants will receive injection of SHP655.
OTHERStandard of Care
Participants will receive PEX as Standard of Care (SOC).
Sponsors
Takeda Development Center Americas, Inc.
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participant or legally authorized representative voluntarily signs informed consent. For participants unable to provide consent, a fully recognized medical proxy may be used according to local laws. * Participant is 18 to 75 years old at the time of screening. * Participant has been diagnosed with primary or secondary autoimmune acquired thrombotic thrombocytopenic purpura (aTTP) based on the following criteria: a) Thrombocytopenia \[drop in platelet count \>=50% or platelet count \<100,000/microlitre (μL)\] i) No more than 3 participants per arm may be enrolled with a screening platelet count \>= 50,000/μL. b) Microangiopathic hemolytic anemia \[elevation of lactate dehydrogenase (LDH) \>2-fold or by presence or increase of schistocytes in peripheral blood smear\]. * Willingness to fully comply with study procedures and requirements, and intention to initiate plasma exchange (PEX). Participants may be provisionally entered into the trial and undergo randomization pending the results of the ADAMTS-13 activity, anti-ADAMTS-13 antibody, and genetic testing for congenital thrombotic thrombocytopenic purpura (cTTP). * If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study. Sexually active males must use an accepted and effective method of contraception during the treatment and until a minimum of 16 days after the last dose administered.
Exclusion criteria
* Participant has been diagnosed with congenital TTP. * Participant has plasma ADAMTS-13 activity \> 10% of normal at the central lab; if screening samples are not taken until after the first PEX, ADAMTS-13 activity from the local lab is permitted to determine eligibility. * Participant has been diagnosed with another cause of thrombotic microangiopathy (TMA) including: DIC, disseminated malignancy, malignant hypertension, hematopoietic stem cell transplantation, shiga toxin related and atypical HUS, drug toxicity (e.g. gemcitabine, mitomycin C, clopidogrel) and pregnancy-related thrombocytopenia syndromes (e.g. HELLP, eclampsia). * Participant has been exposed to another IP within 30 days prior to enrollment or is scheduled to participate in another clinical study involving IP or investigational device during the course of the study. * Participant has received caplacizumab within 1 month prior to study enrollment. * Participant is human immunodeficiency virus positive (HIV+) with unstable disease or CD4+ count \<=200 cells/mm\^3 within 3 months screening. * Participants with conditions of severe immunodeficiency. * Participant has had a previous aTTP event in the past 30 days. * Participant has another underlying progressive fatal disease and/or life expectancy of less than 3 months. * Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures * Participant suffers from a mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study and/or evidence of an uncooperative attitude. However, a fully recognized medical proxy will be permitted to provide consent. * If female, participant is pregnant or lactating. * Participant is a family member or employee of the Sponsor or investigator. * Any contraindication to PEX, methylprednisolone and/or rituximab as per prescribing information. * Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of SHP655.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ADAMTS-13 Activity Levels | Up to Days 11 or 12 | 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). |
| Platelet Count | Baseline and end of study (EOS) (up to approximately 15 months) | The platelet counts are reported in units of 10\^9 per liter blood. |
| Lactate Dehydrogenase (LDH) Levels | Baseline and EOS (up to approximately 15 months) | The lactate dehydrogenase levels are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inhibitory Autoantibodies (Nab) Titer Levels | Baseline and EOS (up to approximately 15 months) | NAb titers were summarized (median, minimum and maximum) at baseline and EOS per treatment arms, in those subjects with NAb positive results (NAb positive is defined as titer value \>=0.6 BU/mL). |
| ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | At Days 3, 7, 10, 21, 28, 42, 56 and 84 | ADAMTS-13 activity levels in participants receiving additional SHP655 for up to 30 days after the resolution of the thrombotic thrombocytopenic purpura (TTP) episode were assessed. Resolution was defined as a normal platelet count and LDH \<2 ULN for at least 48 hours following initial normalization of platelet count (acute episode period). |
| Relationship Between ADAMTS-13 Activity and End-organ Disease Status | Up to 6 months | End-organ disease status were evaluated for renal, cardiac and neurological diseases. |
| Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | Pre-PEX and post-PEX at multiple timepoints at Days 1, 2, 3, 4 or 5, 6 or 7, 8 or 9, and 11 or 12 | — |
| AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Within 15 min pre-PEX and at multiple timepoints Post PEX at Days 1, 2, 3, 4 or 5 and 6 or 7 | — |
| Systemic and Antibody Induced Clearance | 15 minutes pre-PEX,15 minutes post-PEX,15 minutes, 0.5-3 hours, 4-6 hours post end of IP infusion 1,30 minutes pre-IP infusion 2,15 minutes, 0.5-3 hours post-IP infusion 2 of Schedule A or Schedule B (up to 6 months) | — |
| Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Pre-PEX and post-PEX at multiple timepoints at Days 1, 2, 3, 4 or 5, 6 or 7, 8 or 9, and 11 or 12 | — |
| Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Within 15 min pre-PEX and at multiple timepoints Post PEX at Days 2, 3, 4 or 5 and 6 or 7 | — |
| Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Pre-dose at Days 2, 3 4 or 5, 6 or 7, 8 or 9, and 11 or 12 | — |
| Number of Participants Who Achieved Remission Following Normalization of Platelet Count | From the start of study drug administration up to 6 months post remission | Remission was defined as the time taken to achieve platelet count ≥150,000/μL, which was confirmed by a second normal platelet count ≥150,000/μL and LDH \<2 ULN 48 hours following initial normalization. |
| Percentage of Participants Achieving Remission | From the start of study drug administration up to 6 months post remission | Remission was defined as a normal platelet count and LDH \<2 upper limit of normal (ULN) for at least 48 hours following initial normalization of platelet count (acute episode period). Normalization of platelet count was defined ≥150,000/μL, which was confirmed by a second normal platelet count ≥150,000/μL and LDH \<2 ULN. |
| Time to First Exacerbation | From start of study drug administration up to EOS (up to approximately 15 months) | Exacerbation was defined as recurrent thrombocytopenia following a response and requiring a reinitiation of daily plasma exchange treatment after ≥1 day but ≤30 days of no plasma exchange treatment. Data is reported based on Kaplan-Meier estimates. Data was reported for time to first exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS). |
| Time to Relapse | From start of study drug administration up to EOS (up to approximately 15 months) | Relapse was determined by platelet count or the occurrence after remission of a major clinical event (e.g., Myocardial Infraction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for time to relapse in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS). |
| Dose(s) of SHP655 Needed to Achieve and Maintain Adequate Plasma Levels of rADAMTS-13 | From start of study drug administration up to 13 weeks (following remission up to 6 months) | Dose(s) of SHP655 needed to achieve and maintain adequate plasma levels of rADAMTS-13 in order to support induction of remission and to reduce the number of PEX procedures needed for the treatment of acute aTTP episodes was assessed. |
| Percentage of Participants With Relapse | From start of study drug administration up to EOS (up to approximately 15 months) | Relapse was determined by platelet count or the occurrence after remission of a major clinical event (e.g., Myocardial Infraction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for percentage of participants with exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS). |
| Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | From start of study drug administration up to EOS (up to approximately 15 months) | Major clinical events related to TTP included Death, Stroke, MI and organ dysfunction not normalized within the 90-day observation period which consisted of chronic renal insufficiency, neurologic impairment and neurocognitive deficits. |
| Number of Participants With Major Clinical Events Related to PEX | Up to 6 months | Major clinical events included clinically relevant bleeding (modified ITP score) or thrombosis at the site of line insertion, adverse reactions to plasma, including citrate reactions, allergic reactions, and transfusion-related acute lung injury (TRALI). Data is reported by summarizing the data for all parameters. |
| Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline | Baseline and EOS (at approximately Month 15) | — |
| Number of Participants With Inhibitory Antibodies Relative to Baseline | Baseline and EOS (at approximately Month 15) | — |
| Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | Up to 6 months | Percentages are based on the total number of participants per treatment group that have at least one ADA sample analyzed. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | From first dose of study drug until the EOS (up to approximately 15 months) | AE=any untoward medical occurrence in a participants administered IP that does not necessarily have a causal relationship with the treatment. TEAE=an adverse event with an onset that occurs after receiving study drug. SAE=an AE with any untoward clinical manifestation of 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, important medical event, bronchospasm associated with anaphylaxis, reviewed and confirmed seroconversion for human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), or parvovirus B19 (B19V). A product related AE is any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsens. |
| Number of Participants With Clinically Relevant Changes in Vital Signs | From first dose of study drug until the EOS (up to approximately 15 months) | Vital signs were assessed based on blood pressure, pulse rate, respiratory rate and body temperature. |
| Number of Participants With Clinically Relevant Changes in Clinical Chemistry | From first dose of study drug until the EOS (up to approximately 15 months) | Clinical chemistry assessed alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose. |
| Number of Participants With Clinically Relevant Changes in Hematology | From first dose of study drug until the EOS (up to approximately 15 months) | Hematology consisted of complete blood count and leukocytes with differential (basophils, eosinophils, lymphocytes, monocytes, neutrophils), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and platelet count. |
| Percentage of Participants Receiving Rescue Therapy | From first dose of study drug until the EOS (up to approximately 15 months) | Rescue therapy was defined as any product with a known interruption to the pharmacokinetic/ pharmacodynamic (PK/PD) relationship between ADAMTS-13 activity, von Willebrand factor (VWF) activity, and platelet count. If rescue therapy was initiated, the administration of IP (SHP655 or placebo) was suspended for the duration of the study. Number of participants experiencing occurrence of receiving rescue therapy was assessed. |
| Percentage of Participants Meeting Rescue Criteria | From first dose of study drug until the EOS (up to approximately 15 months) | Rescue therapy was defined as any product with a known interruption to the PK/PD relationship between ADAMTS-13 activity, VWF activity, and platelet count. If rescue therapy was initiated, the administration of IP (SHP655 or placebo) was suspended for the duration of the study. Number of participants experiencing occurrence in meeting rescue therapy criteria was assessed. Percentage of participants with rescue therapy initiated are based on laboratory criteria and adverse events. |
| Percentage of Participants With Exacerbation | From start of study drug administration up to EOS (up to approximately 15 months) | Exacerbation was determined by platelet count or the occurrence after remission of a major clinical event (e.g., myocardial infarction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for percentage of participants with exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS). |
| PK/PD Temporal Relationship of Safety and Efficacy Parameter as a Function of ADAMTS-13 Activity | Up to 6 months | Parameters included platelet and LDH counts. |
| Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline and EOS (up to approximately 15 months) | Antibody titer indicates the level of the antibodies in a blood sample, defined as the greatest dilution (or lowest concentration) of the blood sample at which an antibody assay (such as ELISA for e.g.), still produces a detectable positive result. Data is presented per titer for ADA positive participants only. |
Countries
Canada, France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 12 investigative sites in Canada, France, Great Britain, Spain and United States from 09 October 2019 to 05 August 2021.
Pre-assignment details
Participants with a diagnosis of acquired thrombotic thrombocytopenic purpura (aTTP) were enrolled to receive placebo, SHP655 once daily (QD) and twice daily (BID) in a ratio of 1:1:1 in this study .
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care (SoC) + Placebo 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). | 10 |
| SoC + SHP655 + Placebo 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). | 9 |
| SoC + SHP655 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). | 9 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Not Meeting Confirmatory Inclusion Criteria | 0 | 1 | 0 |
| Overall Study | Reason not Specified | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Standard of Care (SoC) + Placebo | SoC + SHP655 + Placebo | SoC + SHP655 | Total |
|---|---|---|---|---|
| Age, Continuous | 41.2 years STANDARD_DEVIATION 10.8 | 51.9 years STANDARD_DEVIATION 14.81 | 48.4 years STANDARD_DEVIATION 14.93 | 47.0 years STANDARD_DEVIATION 13.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 8 Participants | 9 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 4 Participants | 1 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 10 / 10 | 9 / 9 | 6 / 9 |
| serious Total, serious adverse events | 4 / 10 | 1 / 9 | 3 / 9 |
Outcome results
Primary
ADAMTS-13 Activity Levels
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).
Time frame: Up to Days 11 or 12
Population: Pharmacokinetic (PK) Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Overall number analyzed are the number of participants available for analyses. Number analyzed are the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Pre-PEX | 0.1439 international units(IU)/ml | Standard Deviation 0.19247 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post End of IP 2 | 0.4596 international units(IU)/ml | Standard Deviation 0.58498 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post End of IP 2 | 0.2998 international units(IU)/ml | Standard Deviation 0.2496 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post End of IP 2 | 0.2267 international units(IU)/ml | Standard Deviation 0.1866 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤30 min Pre-IP 2 | 0.5045 international units(IU)/ml | Standard Deviation 0.6073 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: 0.5-3 hr Post End of IP 2 | 0.2833 international units(IU)/ml | Standard Deviation 0.23999 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post End of IP 1 | 0.4571 international units(IU)/ml | Standard Deviation 0.19125 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 4-6 hr Post End of IP 1 | 0.5663 international units(IU)/ml | Standard Deviation 0.69581 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Pre-PEX | 0.2468 international units(IU)/ml | Standard Deviation 0.23669 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤30 min Pre-IP 2 | 0.1272 international units(IU)/ml | Standard Deviation 0.2544 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 0.5-3 hr Post End of IP 1 | 0.6699 international units(IU)/ml | Standard Deviation 0.76875 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post-PEX | 0.5342 international units(IU)/ml | Standard Deviation 0.22251 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: 0.5-3 hr Post End of IP 2 | 0.2007 international units(IU)/ml | Standard Deviation 0.20012 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post End of IP 1 | 0.7599 international units(IU)/ml | Standard Deviation 1.0062 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post End of IP 1 | 0.5215 international units(IU)/ml | Standard Deviation 0.23522 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: 0.5-3 Hour (hr) Post End of IP 1 | 0.4420 international units(IU)/ml | Standard Deviation 0.20895 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post-PEX | 0.4554 international units(IU)/ml | Standard Deviation 0.26405 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: 0.5-3 hr Post End of IP 1 | 0.4970 international units(IU)/ml | Standard Deviation 0.23979 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 4-6 hr Post End of IP 1 | 0.1443 international units(IU)/ml | Standard Deviation 0.24485 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Pre-PEX | 0.2378 international units(IU)/ml | Standard Deviation 0.30513 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: 4-6 hr Post End of IP 1 | 0.4670 international units(IU)/ml | Standard Deviation 0.30646 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Pre-PEX | 0.1691 international units(IU)/ml | Standard Deviation 0.15909 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: 0.5-3 hr Post End of IP 2 | 0.3227 international units(IU)/ml | Standard Deviation 0.28191 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤30 min Pre-IP 2 | 0.3424 international units(IU)/ml | Standard Deviation 0.29275 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: 4-6 hr Post End of IP 1 | 0.3197 international units(IU)/ml | Standard Deviation 0.20545 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post End of IP 2 | 0.3514 international units(IU)/ml | Standard Deviation 0.31264 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 0.5-3 hr Post End of IP 1 | 0.2194 international units(IU)/ml | Standard Deviation 0.24929 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post-PEX | 0.5801 international units(IU)/ml | Standard Deviation 0.16107 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 0.5-3 hr Post End of IP 2 | 0.1336 international units(IU)/ml | Standard Deviation 0.2671 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Post End of IP 1 | 0.2150 international units(IU)/ml | Standard Deviation 0.26924 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post End of IP 1 | 0.5433 international units(IU)/ml | Standard Deviation 0.20267 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post-PEX | 0.5418 international units(IU)/ml | Standard Deviation 0.18345 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Post-PEX | 0.2587 international units(IU)/ml | Standard Deviation 0.30131 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: 0.5-3 hr Post End of IP 1 | 0.5281 international units(IU)/ml | Standard Deviation 0.24842 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤30 min Pre-IP 2 | 0.2108 international units(IU)/ml | Standard Deviation 0.19731 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Pre-PEX | 0.1246 international units(IU)/ml | Standard Deviation 0.2491 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: 4-6 hr Post End of IP 1 | 0.4170 international units(IU)/ml | Standard Deviation 0.25202 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 Minutes Post End of IP 2 | 0.1422 international units(IU)/ml | Standard Deviation 0.28435 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 0.5-3 hr Post End of IP 2 | 0.4129 international units(IU)/ml | Standard Deviation 0.49574 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤30 min Pre-IP 2 | 0.3117 international units(IU)/ml | Standard Deviation 0.24934 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Post-PEX | 0.7311 international units(IU)/ml | Standard Deviation 0.48855 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤30 min Pre-IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 0.5-3 hr Post End of IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 8 or 9: ≤15 min Pre-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 8 or 9: ≤15 min Post End of IP 1 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 8 or 9: 0.5-3 hr Post End of IP 1 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 8 or 9: ≤15 min Post End of IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 8 or 9: 0.5-3 hr Post End of IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: 4-6 hr Post End of IP 1 | 1.163 international units(IU)/ml | Standard Deviation 0.61343 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤30 min Pre-IP 2 | 1.027 international units(IU)/ml | Standard Deviation 0.55951 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post End of IP 2 | 1.022 international units(IU)/ml | Standard Deviation 0.5206 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: 0.5-3 hr Post End of IP 2 | 1.015 international units(IU)/ml | Standard Deviation 0.56462 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Pre-PEX | 0.7650 international units(IU)/ml | Standard Deviation 0.61929 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post-PEX | 0.7808 international units(IU)/ml | Standard Deviation 0.36544 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post End of IP 1 | 1.965 international units(IU)/ml | Standard Deviation 0.72122 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: 0.5-3 hr Post End of IP 1 | 2.105 international units(IU)/ml | Standard Deviation 1.0656 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: 4-6 hr Post End of IP 1 | 1.622 international units(IU)/ml | Standard Deviation 0.78046 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤30 min Pre-IP 2 | 1.309 international units(IU)/ml | Standard Deviation 0.48787 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post End of IP 2 | 1.283 international units(IU)/ml | Standard Deviation 0.5255 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 2: 0.5-3 hr Post End of IP 2 | 1.398 international units(IU)/ml | Standard Deviation 0.47591 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Pre-PEX | 1.044 international units(IU)/ml | Standard Deviation 0.54178 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post-PEX | 0.7786 international units(IU)/ml | Standard Deviation 0.16455 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post End of IP 1 | 2.210 international units(IU)/ml | Standard Deviation 0.96057 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: 0.5-3 hr Post End of IP 1 | 2.086 international units(IU)/ml | Standard Deviation 0.85567 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: 4-6 hr Post End of IP 1 | 1.680 international units(IU)/ml | Standard Deviation 0.46457 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤30 min Pre-IP 2 | 1.196 international units(IU)/ml | Standard Deviation 0.4455 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post End of IP 2 | 1.263 international units(IU)/ml | Standard Deviation 0.38468 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 3: 0.5-3 hr Post End of IP 2 | 1.267 international units(IU)/ml | Standard Deviation 0.4358 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Pre-PEX | 1.094 international units(IU)/ml | Standard Deviation 0.67793 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post-PEX | 0.8222 international units(IU)/ml | Standard Deviation 0.21072 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post End of IP 1 | 2.257 international units(IU)/ml | Standard Deviation 0.95791 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 0.5-3 hr Post End of IP 1 | 2.425 international units(IU)/ml | Standard Deviation 1.4869 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 4-6 hr Post End of IP 1 | 1.741 international units(IU)/ml | Standard Deviation 0.84171 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤30 min Pre-IP 2 | 1.290 international units(IU)/ml | Standard Deviation 0.64745 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post End of IP 2 | 1.288 international units(IU)/ml | Standard Deviation 0.63801 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 0.5-3 hr Post End of IP 2 | 1.106 international units(IU)/ml | Standard Deviation 0.59034 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Pre-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 4-6 hr Post End of IP 1 | 1.467 international units(IU)/ml | Standard Deviation 1.1232 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Post End of IP 1 | 1.481 international units(IU)/ml | Standard Deviation 0.89773 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 0.5-3 hr Post End of IP 1 | 1.673 international units(IU)/ml | Standard Deviation 1.0721 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 Minutes Post End of IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 8 or 9: ≤15 min Post-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 8 or 9: 4-6 hr Post End of IP 1 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 8 or 9: ≤30 Minutes Pre-IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 11 or 12: ≤15 min Pre-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 11 or 12: ≤15 min Post-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 11 or 12: ≤30 min Pre-IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 11 or 12: ≤15 min Post End of IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 11 or 12: 0.5-3 hr Post End of IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Pre-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post-PEX | 0.5011 international units(IU)/ml | Standard Deviation 0.19236 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post End of IP 1 | 2.012 international units(IU)/ml | Standard Deviation 0.82832 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels | FRETS: Day 1: 0.5-3 Hour (hr) Post End of IP 1 | 1.905 international units(IU)/ml | Standard Deviation 0.83349 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 2: 4-6 hr Post End of IP 1 | 1.411 international units(IU)/ml | Standard Deviation 0.751 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Pre-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 0.5-3 hr Post End of IP 2 | 2.009 international units(IU)/ml | Standard Deviation 1.4354 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 2: 0.5-3 hr Post End of IP 1 | 2.153 international units(IU)/ml | Standard Deviation 1.3856 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 1: 4-6 hr Post End of IP 1 | 0.7912 international units(IU)/ml | Standard Deviation 0.69403 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Pre-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post End of IP 1 | 1.977 international units(IU)/ml | Standard Deviation 0.98427 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 Minutes Post End of IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Post-PEX | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post-PEX | 0.8426 international units(IU)/ml | Standard Deviation 0.54317 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post-PEX | 0.3029 international units(IU)/ml | Standard Deviation 0.2902 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤15 min Post End of IP 1 | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Pre-PEX | 0.9482 international units(IU)/ml | Standard Deviation 0.99771 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤30 min Pre-IP 2 | 1.041 international units(IU)/ml | Standard Deviation 0.84152 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 0.5-3 hr Post End of IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post End of IP 2 | 1.478 international units(IU)/ml | Standard Deviation 1.0343 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 3: 4-6 hr Post End of IP 1 | 1.271 international units(IU)/ml | Standard Deviation 0.71567 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 0.5-3 hr Post End of IP 1 | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 3: 0.5-3 hr Post End of IP 2 | 1.902 international units(IU)/ml | Standard Deviation 1.4522 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 3: 0.5-3 hr Post End of IP 1 | 1.785 international units(IU)/ml | Standard Deviation 1.1566 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 1: 0.5-3 hr Post End of IP 2 | 1.300 international units(IU)/ml | Standard Deviation 1.1114 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Pre-PEX | 1.378 international units(IU)/ml | Standard Deviation 1.1964 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post End of IP 1 | 1.911 international units(IU)/ml | Standard Deviation 1.6633 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: 4-6 hr Post End of IP 1 | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post-PEX | 0.8725 international units(IU)/ml | Standard Deviation 0.57834 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Post-PEX | 0.7020 international units(IU)/ml | Standard Deviation 0.40432 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post End of IP 2 | 1.545 international units(IU)/ml | Standard Deviation 1.0854 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post End of IP 1 | 1.679 international units(IU)/ml | Standard Deviation 1.3803 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 3: ≤15 min Pre-PEX | 1.129 international units(IU)/ml | Standard Deviation 1.057 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 6 or 7: ≤30 min Pre-IP 2 | NA international units(IU)/ml | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 0.5-3 hr Post End of IP 1 | 1.405 international units(IU)/ml | Standard Deviation 1.0118 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 2: 0.5-3 hr Post End of IP 2 | 2.129 international units(IU)/ml | Standard Deviation 1.4547 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 1: 0.5-3 Hour (hr) Post End of IP 1 | 1.266 international units(IU)/ml | Standard Deviation 0.98904 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: 4-6 hr Post End of IP 1 | 1.214 international units(IU)/ml | Standard Deviation 1.028 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤15 min Post End of IP 2 | 1.960 international units(IU)/ml | Standard Deviation 0.99952 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤30 min Pre-IP 2 | 0.4949 international units(IU)/ml | Standard Deviation 0.54891 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤30 min Pre-IP 2 | 1.255 international units(IU)/ml | Standard Deviation 0.98796 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 2: ≤30 min Pre-IP 2 | 1.044 international units(IU)/ml | Standard Deviation 0.55923 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 1: ≤15 min Post End of IP 1 | 1.352 international units(IU)/ml | Standard Deviation 0.93502 |
| SoC + SHP655 | ADAMTS-13 Activity Levels | FRETS: Day 4 or 5: ≤15 min Post End of IP 2 | 2.306 international units(IU)/ml | Standard Deviation 1.6006 |
Primary
Lactate Dehydrogenase (LDH) Levels
The lactate dehydrogenase levels are reported.
Time frame: Baseline and EOS (up to approximately 15 months)
Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants with data evaluable for analyses. Number analyzed is the number of participants available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care (SoC) + Placebo | Lactate Dehydrogenase (LDH) Levels | EOS | 197.3 international units (IU)/L | Standard Deviation 42 |
| Standard of Care (SoC) + Placebo | Lactate Dehydrogenase (LDH) Levels | Baseline | 634.6 international units (IU)/L | Standard Deviation 378.37 |
| SoC + SHP655 + Placebo | Lactate Dehydrogenase (LDH) Levels | Baseline | 616.3 international units (IU)/L | Standard Deviation 478.14 |
| SoC + SHP655 + Placebo | Lactate Dehydrogenase (LDH) Levels | EOS | 208.8 international units (IU)/L | Standard Deviation 75.2 |
| SoC + SHP655 | Lactate Dehydrogenase (LDH) Levels | Baseline | 787.8 international units (IU)/L | Standard Deviation 188.39 |
| SoC + SHP655 | Lactate Dehydrogenase (LDH) Levels | EOS | 220.4 international units (IU)/L | Standard Deviation 69.93 |
Primary
Platelet Count
The platelet counts are reported in units of 10\^9 per liter blood.
Time frame: Baseline and end of study (EOS) (up to approximately 15 months)
Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants with data evaluable for analyses. Number analyzed is the number of participants available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care (SoC) + Placebo | Platelet Count | Baseline | 35.80 10^9 platelets/L | Standard Deviation 32.076 |
| Standard of Care (SoC) + Placebo | Platelet Count | EOS | 278.89 10^9 platelets/L | Standard Deviation 79.592 |
| SoC + SHP655 + Placebo | Platelet Count | Baseline | 27.67 10^9 platelets/L | Standard Deviation 17.571 |
| SoC + SHP655 + Placebo | Platelet Count | EOS | 267.00 10^9 platelets/L | Standard Deviation 86.906 |
| SoC + SHP655 | Platelet Count | Baseline | 15.38 10^9 platelets/L | Standard Deviation 7.463 |
| SoC + SHP655 | Platelet Count | EOS | 286.22 10^9 platelets/L | Standard Deviation 109.264 |
Secondary
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS
ADAMTS-13 activity levels in participants receiving additional SHP655 for up to 30 days after the resolution of the thrombotic thrombocytopenic purpura (TTP) episode were assessed. Resolution was defined as a normal platelet count and LDH \<2 ULN for at least 48 hours following initial normalization of platelet count (acute episode period).
Time frame: At Days 3, 7, 10, 21, 28, 42, 56 and 84
Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Overall number analyzed are the number of participants available for analyses. Number analyzed is the number of participants with data available for analyses at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 28 | 0.8830 IU/mL | Standard Deviation 0.51516 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 10 | 0.9021 IU/mL | Standard Deviation 0.2052 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 56 | 1.088 IU/mL | Standard Deviation 0.25524 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 21 | 0.8102 IU/mL | Standard Deviation 0.52773 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 3 | 0.4602 IU/mL | Standard Deviation 0.14328 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 84 | 0.9708 IU/mL | Standard Deviation 0.43831 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 42 | 0.9968 IU/mL | Standard Deviation 0.36745 |
| Standard of Care (SoC) + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 7 | 0.3037 IU/mL | Standard Deviation 0.26921 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 21 | 0.6264 IU/mL | Standard Deviation 0.60971 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 3 | NA IU/mL | — |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 7 | 0.3180 IU/mL | Standard Deviation 0.34714 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 10 | 0.5518 IU/mL | Standard Deviation 0.33962 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 28 | 0.8931 IU/mL | Standard Deviation 0.41323 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 42 | 0.8842 IU/mL | Standard Deviation 0.39784 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 56 | 0.9923 IU/mL | Standard Deviation 0.33663 |
| SoC + SHP655 + Placebo | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 84 | 1.021 IU/mL | Standard Deviation 0.65715 |
| SoC + SHP655 | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 3 | 0.1171 IU/mL | Standard Deviation 0.28688 |
| SoC + SHP655 | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 10 | 0.4904 IU/mL | Standard Deviation 0.46441 |
| SoC + SHP655 | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 42 | 1.055 IU/mL | Standard Deviation 0.3608 |
| SoC + SHP655 | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 84 | 0.6051 IU/mL | Standard Deviation 0.48113 |
| SoC + SHP655 | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 7 | NA IU/mL | — |
| SoC + SHP655 | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 21 | 0.5320 IU/mL | Standard Deviation 0.51432 |
| SoC + SHP655 | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 56 | 1.092 IU/mL | Standard Deviation 0.19961 |
| SoC + SHP655 | ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS | Day 28 | 0.8632 IU/mL | Standard Deviation 0.62848 |
Secondary
AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS
Time frame: Within 15 min pre-PEX and at multiple timepoints Post PEX at Days 1, 2, 3, 4 or 5 and 6 or 7
Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Number analyzed are the number of participants available for analysis at the specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care (SoC) + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 4 or 5 | 9.507 h*IU/mL | Standard Deviation 11.592 |
| Standard of Care (SoC) + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 3 | 5.590 h*IU/mL | Standard Deviation 4.7232 |
| Standard of Care (SoC) + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 1 | 3.563 h*IU/mL | Standard Deviation 2.5551 |
| Standard of Care (SoC) + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 2 | 4.461 h*IU/mL | Standard Deviation 3.948 |
| Standard of Care (SoC) + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 6 or 7 | NA h*IU/mL | — |
| SoC + SHP655 + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 3 | 22.75 h*IU/mL | Standard Deviation 5.6549 |
| SoC + SHP655 + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 1 | 19.87 h*IU/mL | Standard Deviation 9.115 |
| SoC + SHP655 + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 2 | 24.16 h*IU/mL | Standard Deviation 9.0323 |
| SoC + SHP655 + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 4 or 5 | 24.10 h*IU/mL | Standard Deviation 11.357 |
| SoC + SHP655 + Placebo | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 6 or 7 | NA h*IU/mL | — |
| SoC + SHP655 | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 6 or 7 | NA h*IU/mL | — |
| SoC + SHP655 | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 4 or 5 | 22.05 h*IU/mL | Standard Deviation 14.192 |
| SoC + SHP655 | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 1 | 12.80 h*IU/mL | Standard Deviation 8.4633 |
| SoC + SHP655 | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 3 | 23.49 h*IU/mL | Standard Deviation 9.2589 |
| SoC + SHP655 | AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS | Day 2 | 21.97 h*IU/mL | Standard Deviation 11.135 |
Secondary
Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS
Time frame: Pre-PEX and post-PEX at multiple timepoints at Days 1, 2, 3, 4 or 5, 6 or 7, 8 or 9, and 11 or 12
Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Number analyzed is the number of participants available for analyses at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care (SoC) + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 1 | 0.4157 IU/mL | Standard Deviation 0.17075 |
| Standard of Care (SoC) + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 6 or 7 | 0.1362 IU/mL | Standard Deviation 0.095283 |
| Standard of Care (SoC) + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 3 | 0.4307 IU/mL | Standard Deviation 0.2842 |
| Standard of Care (SoC) + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 4 or 5 | 0.6438 IU/mL | Standard Deviation 0.97767 |
| Standard of Care (SoC) + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 2 | 0.4951 IU/mL | Standard Deviation 0.27178 |
| SoC + SHP655 + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 8 or 9 | NA IU/mL | — |
| SoC + SHP655 + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 1 | 2.011 IU/mL | Standard Deviation 0.79036 |
| SoC + SHP655 + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 2 | 2.153 IU/mL | Standard Deviation 1.1404 |
| SoC + SHP655 + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 3 | 2.228 IU/mL | Standard Deviation 0.93968 |
| SoC + SHP655 + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 4 or 5 | 2.633 IU/mL | Standard Deviation 1.4955 |
| SoC + SHP655 + Placebo | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 6 or 7 | 1.625 IU/mL | Standard Deviation 1.0126 |
| SoC + SHP655 | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 4 or 5 | 2.377 IU/mL | Standard Deviation 1.5934 |
| SoC + SHP655 | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 2 | 2.458 IU/mL | Standard Deviation 1.4369 |
| SoC + SHP655 | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 1 | 1.653 IU/mL | Standard Deviation 1.0655 |
| SoC + SHP655 | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 3 | 2.222 IU/mL | Standard Deviation 1.508 |
| SoC + SHP655 | Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS | Day 6 or 7 | NA IU/mL | — |
Secondary
Dose(s) of SHP655 Needed to Achieve and Maintain Adequate Plasma Levels of rADAMTS-13
Dose(s) of SHP655 needed to achieve and maintain adequate plasma levels of rADAMTS-13 in order to support induction of remission and to reduce the number of PEX procedures needed for the treatment of acute aTTP episodes was assessed.
Time frame: From start of study drug administration up to 13 weeks (following remission up to 6 months)
Population: Data could not be analyzed due to sparse sample collections and confounding dosing inputs with daily sequential PEX + SHP655 dosing.
Secondary
Inhibitory Autoantibodies (Nab) Titer Levels
NAb titers were summarized (median, minimum and maximum) at baseline and EOS per treatment arms, in those subjects with NAb positive results (NAb positive is defined as titer value \>=0.6 BU/mL).
Time frame: Baseline and EOS (up to approximately 15 months)
Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants with data evaluable for analyses. Number analyzed is the number of participants available for analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Inhibitory Autoantibodies (Nab) Titer Levels | Baseline | 1.25 BU/mL |
| Standard of Care (SoC) + Placebo | Inhibitory Autoantibodies (Nab) Titer Levels | EOS | 0.60 BU/mL |
| SoC + SHP655 + Placebo | Inhibitory Autoantibodies (Nab) Titer Levels | Baseline | 1.25 BU/mL |
| SoC + SHP655 + Placebo | Inhibitory Autoantibodies (Nab) Titer Levels | EOS | 0.70 BU/mL |
| SoC + SHP655 | Inhibitory Autoantibodies (Nab) Titer Levels | Baseline | 1.80 BU/mL |
| SoC + SHP655 | Inhibitory Autoantibodies (Nab) Titer Levels | EOS | 4.00 BU/mL |
Secondary
Number of Participants Who Achieved Remission Following Normalization of Platelet Count
Remission was defined as the time taken to achieve platelet count ≥150,000/μL, which was confirmed by a second normal platelet count ≥150,000/μL and LDH \<2 ULN 48 hours following initial normalization.
Time frame: From the start of study drug administration up to 6 months post remission
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants Who Achieved Remission Following Normalization of Platelet Count | 9 Participants |
| SoC + SHP655 + Placebo | Number of Participants Who Achieved Remission Following Normalization of Platelet Count | 8 Participants |
| SoC + SHP655 | Number of Participants Who Achieved Remission Following Normalization of Platelet Count | 8 Participants |
Secondary
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer
Antibody titer indicates the level of the antibodies in a blood sample, defined as the greatest dilution (or lowest concentration) of the blood sample at which an antibody assay (such as ELISA for e.g.), still produces a detectable positive result. Data is presented per titer for ADA positive participants only.
Time frame: Baseline and EOS (up to approximately 15 months)
Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants are ADA positive participants. Number analyzed is the number of participants available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:20 | 2 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:40 | 2 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:80 | 1 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:2560 | 0 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:320 | 0 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:40 | 3 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:81920 | 0 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:640 | 0 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:80 | 2 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:160 | 0 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:5120 | 0 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:1280 | 0 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:20 | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:5120 | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:20 | 1 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:40 | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:20 | 3 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:80 | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:80 | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:1280 | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:2560 | 1 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:160 | 1 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:640 | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:320 | 2 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:81920 | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:40 | 2 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:81920 | 1 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:80 | 1 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:320 | 0 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:20 | 1 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:40 | 2 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:160 | 2 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:640 | 1 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | Baseline- 1:1280 | 1 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:20 | 0 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:40 | 1 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:2560 | 0 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:5120 | 1 Participants |
| SoC + SHP655 | Number of Participants With ADAMTS-13 Binding Antibodies Per Titer | EOS- 1:80 | 2 Participants |
Secondary
Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline
Time frame: Baseline and EOS (at approximately Month 15)
Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants available for analyses. Number analyzed are the number of participants with data available for analysis at the specific time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline | Baseline | 7 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline | EOS at Month 15 | 3 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline | Baseline | 8 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline | EOS at Month 15 | 2 Participants |
| SoC + SHP655 | Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline | Baseline | 8 Participants |
| SoC + SHP655 | Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline | EOS at Month 15 | 5 Participants |
Secondary
Number of Participants With Clinically Relevant Changes in Clinical Chemistry
Clinical chemistry assessed alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose.
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Population: SAS included all participants randomized, who received any dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants With Clinically Relevant Changes in Clinical Chemistry | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Clinically Relevant Changes in Clinical Chemistry | 0 Participants |
| SoC + SHP655 | Number of Participants With Clinically Relevant Changes in Clinical Chemistry | 0 Participants |
Secondary
Number of Participants With Clinically Relevant Changes in Hematology
Hematology consisted of complete blood count and leukocytes with differential (basophils, eosinophils, lymphocytes, monocytes, neutrophils), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and platelet count.
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Population: SAS included all participants randomized, who received any dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants With Clinically Relevant Changes in Hematology | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Clinically Relevant Changes in Hematology | 0 Participants |
| SoC + SHP655 | Number of Participants With Clinically Relevant Changes in Hematology | 0 Participants |
Secondary
Number of Participants With Clinically Relevant Changes in Vital Signs
Vital signs were assessed based on blood pressure, pulse rate, respiratory rate and body temperature.
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Population: SAS included all participants randomized, who received any dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants With Clinically Relevant Changes in Vital Signs | 0 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Clinically Relevant Changes in Vital Signs | 0 Participants |
| SoC + SHP655 | Number of Participants With Clinically Relevant Changes in Vital Signs | 0 Participants |
Secondary
Number of Participants With Inhibitory Antibodies Relative to Baseline
Time frame: Baseline and EOS (at approximately Month 15)
Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants available for analyses. Number analyzed are the number of participants with data available for analysis at the specific time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants With Inhibitory Antibodies Relative to Baseline | Baseline | 6 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With Inhibitory Antibodies Relative to Baseline | EOS at Month 15 | 3 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Inhibitory Antibodies Relative to Baseline | Baseline | 4 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Inhibitory Antibodies Relative to Baseline | EOS at Month 15 | 3 Participants |
| SoC + SHP655 | Number of Participants With Inhibitory Antibodies Relative to Baseline | Baseline | 7 Participants |
| SoC + SHP655 | Number of Participants With Inhibitory Antibodies Relative to Baseline | EOS at Month 15 | 2 Participants |
Secondary
Number of Participants With Major Clinical Events Related to PEX
Major clinical events included clinically relevant bleeding (modified ITP score) or thrombosis at the site of line insertion, adverse reactions to plasma, including citrate reactions, allergic reactions, and transfusion-related acute lung injury (TRALI). Data is reported by summarizing the data for all parameters.
Time frame: Up to 6 months
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants With Major Clinical Events Related to PEX | 6 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Major Clinical Events Related to PEX | 1 Participants |
| SoC + SHP655 | Number of Participants With Major Clinical Events Related to PEX | 1 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs
AE=any untoward medical occurrence in a participants administered IP that does not necessarily have a causal relationship with the treatment. TEAE=an adverse event with an onset that occurs after receiving study drug. SAE=an AE with any untoward clinical manifestation of 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, important medical event, bronchospasm associated with anaphylaxis, reviewed and confirmed seroconversion for human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), or parvovirus B19 (B19V). A product related AE is any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsens.
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Population: SAS included all participants randomized, who received any dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Specifically Product-Related TEAEs | 0 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Any TEAEs | 10 Participants |
| Standard of Care (SoC) + Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Serious TEAEs | 4 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Specifically Product-Related TEAEs | 1 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Any TEAEs | 9 Participants |
| SoC + SHP655 + Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Serious TEAEs | 1 Participants |
| SoC + SHP655 | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Any TEAEs | 8 Participants |
| SoC + SHP655 | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Serious TEAEs | 3 Participants |
| SoC + SHP655 | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs | Specifically Product-Related TEAEs | 0 Participants |
Secondary
Percentage of Participants Achieving Remission
Remission was defined as a normal platelet count and LDH \<2 upper limit of normal (ULN) for at least 48 hours following initial normalization of platelet count (acute episode period). Normalization of platelet count was defined ≥150,000/μL, which was confirmed by a second normal platelet count ≥150,000/μL and LDH \<2 ULN.
Time frame: From the start of study drug administration up to 6 months post remission
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample. Overall number analyzed are the number of participants with data evaluable for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care (SoC) + Placebo | Percentage of Participants Achieving Remission | 100.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants Achieving Remission | 100.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants Achieving Remission | 88.9 percentage of participants |
Secondary
Percentage of Participants Meeting Rescue Criteria
Rescue therapy was defined as any product with a known interruption to the PK/PD relationship between ADAMTS-13 activity, VWF activity, and platelet count. If rescue therapy was initiated, the administration of IP (SHP655 or placebo) was suspended for the duration of the study. Number of participants experiencing occurrence in meeting rescue therapy criteria was assessed. Percentage of participants with rescue therapy initiated are based on laboratory criteria and adverse events.
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care (SoC) + Placebo | Percentage of Participants Meeting Rescue Criteria | 10.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants Meeting Rescue Criteria | 0.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants Meeting Rescue Criteria | 11.1 percentage of participants |
Secondary
Percentage of Participants Receiving Rescue Therapy
Rescue therapy was defined as any product with a known interruption to the pharmacokinetic/ pharmacodynamic (PK/PD) relationship between ADAMTS-13 activity, von Willebrand factor (VWF) activity, and platelet count. If rescue therapy was initiated, the administration of IP (SHP655 or placebo) was suspended for the duration of the study. Number of participants experiencing occurrence of receiving rescue therapy was assessed.
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care (SoC) + Placebo | Percentage of Participants Receiving Rescue Therapy | 20.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants Receiving Rescue Therapy | 0 percentage of participants |
| SoC + SHP655 | Percentage of Participants Receiving Rescue Therapy | 22.2 percentage of participants |
Secondary
Percentage of Participants With ADAMTS-13 Activity Trough Levels >10%
Time frame: Pre-dose at Days 2, 3 4 or 5, 6 or 7, 8 or 9, and 11 or 12
Population: PK Set:all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value.Overall number:particiapnts from PK set,included number of participants available for analysis.Number analyzed:number of participants available with ADAMTS activity absolute Ctrough values at given time point.Percentages are calculated based on total number of participants available for corresponding stratification per day.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 3 | 57.1 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 2 | 57.1 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 4 or 5 | 50.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 6 or 7 | 33.3 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 11 or 12 | 100.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 2 | 100.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 3 | 100.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 4 or 5 | 100.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 6 or 7 | 66.7 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 8 or 9 | 100.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 4 or 5 | 100.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 3 | 85.7 percentage of participants |
| SoC + SHP655 | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 6 or 7 | 50.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% | Day 2 | 77.8 percentage of participants |
Secondary
Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655
Percentages are based on the total number of participants per treatment group that have at least one ADA sample analyzed.
Time frame: Up to 6 months
Population: Full Analysis Set (FAS) included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | Nab Positive: up to 3 Months | 40.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | ADA Positive: up to 6 Months | 20.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | Nab Positive: up to 6 Months | 30.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | ADA Positive: up to 3 Months | 80.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | ADA Positive: up to 6 Months | 75.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | Nab Positive: up to 6 Months | 37.5 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | ADA Positive: up to 3 Months | 62.5 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | Nab Positive: up to 3 Months | 37.5 percentage of participants |
| SoC + SHP655 | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | ADA Positive: up to 3 Months | 88.9 percentage of participants |
| SoC + SHP655 | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | Nab Positive: up to 6 Months | 22.2 percentage of participants |
| SoC + SHP655 | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | Nab Positive: up to 3 Months | 33.3 percentage of participants |
| SoC + SHP655 | Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 | ADA Positive: up to 6 Months | 33.3 percentage of participants |
Secondary
Percentage of Participants With Exacerbation
Exacerbation was determined by platelet count or the occurrence after remission of a major clinical event (e.g., myocardial infarction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for percentage of participants with exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS).
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample. Overall number of participants analyzed are number of participants achieving remission. Number analyzed are the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Percentage of Participants With Exacerbation | From Study Start up to 11 Months | 50.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With Exacerbation | From 11 Months up to EOS (up to approximately 15 months) | 33.3 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With Exacerbation | From Study Start up to 11 Months | 0.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With Exacerbation | From 11 Months up to EOS (up to approximately 15 months) | 0.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With Exacerbation | From Study Start up to 11 Months | 60.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With Exacerbation | From 11 Months up to EOS (up to approximately 15 months) | 33.3 percentage of participants |
Secondary
Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP)
Major clinical events related to TTP included Death, Stroke, MI and organ dysfunction not normalized within the 90-day observation period which consisted of chronic renal insufficiency, neurologic impairment and neurocognitive deficits.
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Renal Insufficiency | 90.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Neurologic Deficits | 60.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Brain Injury | 50.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Death, Stroke and MI | 0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Death, Stroke and MI | 0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Renal Insufficiency | 100.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Brain Injury | 62.5 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Neurologic Deficits | 100.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Death, Stroke and MI | 0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Neurologic Deficits | 77.8 percentage of participants |
| SoC + SHP655 | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Brain Injury | 66.7 percentage of participants |
| SoC + SHP655 | Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) | Renal Insufficiency | 88.9 percentage of participants |
Secondary
Percentage of Participants With Relapse
Relapse was determined by platelet count or the occurrence after remission of a major clinical event (e.g., Myocardial Infraction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for percentage of participants with exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS).
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Percentage of Participants With Relapse | From Study Start up to 11 Months | 0.0 percentage of participants |
| Standard of Care (SoC) + Placebo | Percentage of Participants With Relapse | From 11 Months up to EOS (up to approximately 15 months) | 0.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With Relapse | From Study Start up to 11 Months | 0.0 percentage of participants |
| SoC + SHP655 + Placebo | Percentage of Participants With Relapse | From 11 Months up to EOS (up to approximately 15 months) | 0.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With Relapse | From Study Start up to 11 Months | 0.0 percentage of participants |
| SoC + SHP655 | Percentage of Participants With Relapse | From 11 Months up to EOS (up to approximately 15 months) | 0.0 percentage of participants |
Secondary
PK/PD Temporal Relationship of Safety and Efficacy Parameter as a Function of ADAMTS-13 Activity
Parameters included platelet and LDH counts.
Time frame: Up to 6 months
Population: Data could not be analyzed due to sparse sample collections and confounding dosing inputs with daily sequential PEX + SHP655 dosing.
Secondary
Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio
Time frame: Pre-PEX and post-PEX at multiple timepoints at Days 1, 2, 3, 4 or 5, 6 or 7, 8 or 9, and 11 or 12
Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Overall number analyzed are the number of participants available for analyses. Number analyzed is the number of participants with data available for analyses at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care (SoC) + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 6 or 7 | NA ratio | — |
| Standard of Care (SoC) + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 3 | 1.669 ratio | Standard Deviation 0.34045 |
| Standard of Care (SoC) + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 2 | 2.587 ratio | Standard Deviation 0.92176 |
| Standard of Care (SoC) + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 4 or 5 | NA ratio | — |
| Standard of Care (SoC) + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 1 | 2.744 ratio | Standard Deviation 3.3837 |
| SoC + SHP655 + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 8 or 9 | NA ratio | — |
| SoC + SHP655 + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 1 | NA ratio | — |
| SoC + SHP655 + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 2 | 3.534 ratio | Standard Deviation 2.4373 |
| SoC + SHP655 + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 3 | 2.134 ratio | Standard Deviation 0.45392 |
| SoC + SHP655 + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 4 or 5 | 2.543 ratio | Standard Deviation 0.59576 |
| SoC + SHP655 + Placebo | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 6 or 7 | NA ratio | — |
| SoC + SHP655 | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 4 or 5 | 1.972 ratio | Standard Deviation 0.91248 |
| SoC + SHP655 | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 2 | 3.675 ratio | Standard Deviation 2.338 |
| SoC + SHP655 | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 1 | NA ratio | — |
| SoC + SHP655 | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 3 | 2.268 ratio | Standard Deviation 1.0679 |
| SoC + SHP655 | Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio | FRETS: Day 6 or 7 | NA ratio | — |
Secondary
Relationship Between ADAMTS-13 Activity and End-organ Disease Status
End-organ disease status were evaluated for renal, cardiac and neurological diseases.
Time frame: Up to 6 months
Population: Data could not be analyzed due to sparse sample collections and confounding dosing inputs with daily sequential PEX + SHP655 dosing.
Secondary
Systemic and Antibody Induced Clearance
Time frame: 15 minutes pre-PEX,15 minutes post-PEX,15 minutes, 0.5-3 hours, 4-6 hours post end of IP infusion 1,30 minutes pre-IP infusion 2,15 minutes, 0.5-3 hours post-IP infusion 2 of Schedule A or Schedule B (up to 6 months)
Population: Data could not be analyzed due to sparse sample collections and confounding dosing inputs with daily sequential PEX + SHP655 dosing.
Secondary
Time to First Exacerbation
Exacerbation was defined as recurrent thrombocytopenia following a response and requiring a reinitiation of daily plasma exchange treatment after ≥1 day but ≤30 days of no plasma exchange treatment. Data is reported based on Kaplan-Meier estimates. Data was reported for time to first exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS).
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Time to First Exacerbation | From Study Start up to 11 Months | NA days |
| Standard of Care (SoC) + Placebo | Time to First Exacerbation | From 11 Months up to EOS (up to approximately 15 months) | NA days |
| SoC + SHP655 + Placebo | Time to First Exacerbation | From Study Start up to 11 Months | NA days |
| SoC + SHP655 + Placebo | Time to First Exacerbation | From 11 Months up to EOS (up to approximately 15 months) | NA days |
| SoC + SHP655 | Time to First Exacerbation | From Study Start up to 11 Months | 8.0 days |
| SoC + SHP655 | Time to First Exacerbation | From 11 Months up to EOS (up to approximately 15 months) | NA days |
Secondary
Time to Relapse
Relapse was determined by platelet count or the occurrence after remission of a major clinical event (e.g., Myocardial Infraction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for time to relapse in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS).
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care (SoC) + Placebo | Time to Relapse | From Study Start up to 11 Months | NA days |
| Standard of Care (SoC) + Placebo | Time to Relapse | From 11 Months up to EOS (up to approximately 15 months) | NA days |
| SoC + SHP655 + Placebo | Time to Relapse | From Study Start up to 11 Months | NA days |
| SoC + SHP655 + Placebo | Time to Relapse | From 11 Months up to EOS (up to approximately 15 months) | NA days |
| SoC + SHP655 | Time to Relapse | From Study Start up to 11 Months | NA days |
| SoC + SHP655 | Time to Relapse | From 11 Months up to EOS (up to approximately 15 months) | NA days |
Secondary
Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS
Time frame: Within 15 min pre-PEX and at multiple timepoints Post PEX at Days 2, 3, 4 or 5 and 6 or 7
Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Overall number analyzed are the number of participants available for analyses. Number analyzed are the number of participants with data available for analysis at the specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care (SoC) + Placebo | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 2 | 0.1667 IU/mL | Standard Deviation 0.17308 |
| Standard of Care (SoC) + Placebo | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 3 | 0.2579 IU/mL | Standard Deviation 0.26836 |
| Standard of Care (SoC) + Placebo | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 4 or 5 | 0.3138 IU/mL | Standard Deviation 0.38416 |
| Standard of Care (SoC) + Placebo | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 6 or 7 | 0.1660 IU/mL | Standard Deviation 0.28752 |
| SoC + SHP655 + Placebo | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 6 or 7 | 1.070 IU/mL | Standard Deviation 0.98879 |
| SoC + SHP655 + Placebo | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 2 | 0.8493 IU/mL | Standard Deviation 0.62139 |
| SoC + SHP655 + Placebo | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 4 or 5 | 1.180 IU/mL | Standard Deviation 0.65905 |
| SoC + SHP655 + Placebo | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 3 | 1.110 IU/mL | Standard Deviation 0.52612 |
| SoC + SHP655 | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 6 or 7 | NA IU/mL | — |
| SoC + SHP655 | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 3 | 1.174 IU/mL | Standard Deviation 0.9391 |
| SoC + SHP655 | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 4 or 5 | 1.378 IU/mL | Standard Deviation 1.1976 |
| SoC + SHP655 | Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS | Day 2 | 0.9274 IU/mL | Standard Deviation 0.93426 |