Acquired Thrombotic Thrombocytopenic Purpura (aTTP)Phase 2SOAR-HINCT03922308
Study of rADAMTS-13 (SHP655) in the Treatment of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
A Phase 2 study testing SHP655 in people with Acquired Thrombotic Thrombocytopenic Purpura (aTTP), run by Shire at 24 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
- What is being tested?
- SHP655
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 24 sitesin 7 countries
- Study dates
- 9 Oct 2019to 5 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
24 sites in 7 countries.
24 sites in 7 countries
United States7 sites
The University of Alabama at Birmingham
Birmingham, Alabama, 35249
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106-4948
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
University of Minnesota
Minneapolis, Minnesota, 55455
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Spain5 sites
Hospital General Universitario de Alicante
Alicante, 03010
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Dr. Peset
Valencia, 46017
Hospital Universitari i Politècnic la Fe
Valencia, 46026
France4 sites
Hopital Conception
Marseille, 13005
Chu Saint-Antoine
Paris, 75012
CHU de Reims - Hôpital Maison Blanche
Reims, Marne, 51092
CHU de Rouen
Seine Maritime, 76031
United Kingdom3 sites
University Hospital of Wales
Cardiff, West Glamorgan, CF14 4XW
Royal Liverpool University Hospital
Liverpool, L7 8XP
1st Floor, UCLH-Haematology
London, WC1E 6HX
Canada2 sites
London Health Sciences Centre (LHSC) - University Hospital
London, Ontario, N6A 5A5
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Italy2 sites
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
Milan, 20122
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, 137
About this study
Official title: A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-blind Study in Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) to Evaluate the Pharmacokinetics, Safety and Efficacy of rADAMTS-13 (SHP655) Administered in Addition to Standard Of Care (SoC) Treatment
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.
- Being tested
- Placebo, SHP655, Standard of Care
- Medical subject headings
- Purpura, Thrombotic Thrombocytopenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Participants will receive injection of placebo matched to SHP655.
SHP655Drug
Also called rADAMTS-13
Participants will receive injection of SHP655.
Standard of CareOther
Also called PEX
Participants will receive PEX as Standard of Care (SOC).
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care (SoC) + Placebo | Placebo comparator | Participants received SoC daily PEX followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months). Receives: Other: Placebo; Other: Standard of Care |
| SoC + SHP655 + Placebo | Experimental | Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months). Receives: Other: Placebo; Drug: SHP655; Other: Standard of Care |
| SoC + SHP655 | Experimental | Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months). Receives: Drug: SHP655; Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to Days 11 or 12
Platelet Count
The platelet counts are reported in units of 10^9 per liter blood.
Measured: Baseline and end of study (EOS) (up to approximately 15 months)
Lactate Dehydrogenase (LDH) Levels
The lactate dehydrogenase levels are reported.
Measured: Baseline and EOS (up to approximately 15 months)
Secondary outcomes (29)
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.
Measured: From start of study drug administration up to 13 weeks (following remission up to 6 months)
PK/PD Temporal Relationship of Safety and Efficacy Parameter as a Function of ADAMTS-13 Activity
Parameters included platelet and LDH counts.
Measured: Up to 6 months
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.
Measured: Baseline and EOS (up to approximately 15 months)
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).
Measured: Baseline and EOS (up to approximately 15 months)
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).
Measured: At Days 3, 7, 10, 21, 28, 42, 56 and 84
Relationship Between ADAMTS-13 Activity and End-organ Disease Status
End-organ disease status were evaluated for renal, cardiac and neurological diseases.
Measured: Up to 6 months
Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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%
Measured: 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
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.
Measured: From the start of study drug administration up to 6 months post remission
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.
Measured: From the start of study drug administration up to 6 months post remission
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).
Measured: From start of study drug administration up to EOS (up to approximately 15 months)
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).
Measured: From start of study drug administration up to EOS (up to approximately 15 months)
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).
Measured: From start of study drug administration up to EOS (up to approximately 15 months)
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).
Measured: From start of study drug administration up to EOS (up to approximately 15 months)
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.
Measured: From start of study drug administration up to EOS (up to approximately 15 months)
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.
Measured: Up to 6 months
Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline
Measured: Baseline and EOS (at approximately Month 15)
Number of Participants With Inhibitory Antibodies Relative to Baseline
Measured: Baseline and EOS (at approximately Month 15)
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.
Measured: Up to 6 months
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.
Measured: From first dose of study drug until the EOS (up to approximately 15 months)
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.
Measured: From first dose of study drug until the EOS (up to approximately 15 months)
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.
Measured: From first dose of study drug until the EOS (up to approximately 15 months)
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.
Measured: From first dose of study drug until the EOS (up to approximately 15 months)
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.
Measured: From first dose of study drug until the EOS (up to approximately 15 months)
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.
Measured: From first dose of study drug until the EOS (up to approximately 15 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2019
- Study start9 Oct 2019
- Primary completion5 Aug 2021
- Study completion5 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acquired Thrombotic Thrombocytopenic Purpura (aTTP)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03922308
- Sponsor's protocol ID
- SHP655-201
- Other IDs
- 2018-003775-35, 2018
- Acronym
- SOAR-HI
- Status last verified
- Nov 2022
- First submitted
- 5 Apr 2019
- Last updated
- 1 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-blind Study in Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) to Evaluate the Pharmacokinetics, Safety and Efficacy of rADAMTS-13 (SHP655) Administered in Addition to Standard Of Care (SoC) Treatment
- ClinicalTrials.gov ID
- NCT03922308
- Acronym / sponsor ID
- SOAR-HI / SHP655-201
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 9 Oct 2019 (actual)
- Primary completion
- 5 Aug 2021 (actual)
- Study completion
- 5 Aug 2021 (actual)
- First posted
- 19 Apr 2019 (actual)
- Results
- Posted 1 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the pharmacokinetics, safety, and efficacy of rADAMTS-13 (SHP655) administered in addition to standard of care (SoC) treatment of acquired thrombotic thrombocytopenic purpura (aTTP) participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard of Care (SoC) + Placebo | Placebo comparator | Other: Placebo, Other: Standard of CareParticipants received SoC daily PEX followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months). |
| SoC + SHP655 + Placebo | Experimental | Other: Placebo, Drug: SHP655, Other: Standard of CareParticipants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months). |
| SoC + SHP655 | Experimental | Drug: SHP655, Other: Standard of CareParticipants 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboParticipants will receive injection of placebo matched to SHP655. | Other | SoC + SHP655 + Placebo, Standard of Care (SoC) + Placebo |
| SHP655Also: rADAMTS-13Participants will receive injection of SHP655. | Drug | SoC + SHP655, SoC + SHP655 + Placebo |
| Standard of CareAlso: PEXParticipants will receive PEX as Standard of Care (SOC). | Other | SoC + SHP655, SoC + SHP655 + Placebo, Standard of Care (SoC) + Placebo |
Primary outcome
ADAMTS-13 Activity Levels
Time frame: 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
Time frame: 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
Time frame: Baseline and EOS (up to approximately 15 months)
The lactate dehydrogenase levels are reported.
29 secondary outcomes
Dose(s) of SHP655 Needed to Achieve and Maintain Adequate Plasma Levels of rADAMTS-13
Time frame: From start of study drug administration up to 13 weeks (following remission up to 6 months)
PK/PD Temporal Relationship of Safety and Efficacy Parameter as a Function of ADAMTS-13 Activity
Time frame: Up to 6 months
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer
Time frame: Baseline and EOS (up to approximately 15 months)
Inhibitory Autoantibodies (Nab) Titer Levels
Time frame: Baseline and EOS (up to approximately 15 months)
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS
Time frame: At Days 3, 7, 10, 21, 28, 42, 56 and 84
Relationship Between ADAMTS-13 Activity and End-organ Disease Status
Time frame: Up to 6 months
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
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
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)
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
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
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
Number of Participants Who Achieved Remission Following Normalization of Platelet Count
Time frame: From the start of study drug administration up to 6 months post remission
Percentage of Participants Achieving Remission
Time frame: From the start of study drug administration up to 6 months post remission
Time to First Exacerbation
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Time to Relapse
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Percentage of Participants With Exacerbation
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Percentage of Participants With Relapse
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP)
Time frame: From start of study drug administration up to EOS (up to approximately 15 months)
Number of Participants With Major Clinical Events Related to PEX
Time frame: Up to 6 months
Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline
Time frame: Baseline and EOS (at approximately Month 15)
Number of Participants With Inhibitory Antibodies Relative to Baseline
Time frame: Baseline and EOS (at approximately Month 15)
Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655
Time frame: Up to 6 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Number of Participants With Clinically Relevant Changes in Vital Signs
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Number of Participants With Clinically Relevant Changes in Clinical Chemistry
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Number of Participants With Clinically Relevant Changes in Hematology
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Percentage of Participants Receiving Rescue Therapy
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Percentage of Participants Meeting Rescue Criteria
Time frame: From first dose of study drug until the EOS (up to approximately 15 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain more information on the study, click here/on this linkLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Shire
24 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SHP655 in people with Acquired Thrombotic Thrombocytopenic Purpura (aTTP), run by Shire at 24 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Spain, France, United Kingdom, Canada and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ADAMTS-13 Activity Levels (time frame: Up to Days 11 or 12). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2022.