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Follow-up Study for Patients Who Completed Study ALX0681-C301 (Post-HERCULES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02878603
Recruitment Status : Completed
First Posted : August 25, 2016
Results First Posted : November 22, 2021
Last Update Posted : March 28, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:
The objectives of this study were to evaluate long-term safety and efficacy of caplacizumab, to evaluate safety and efficacy of repeated use of caplacizumab and to characterize long-term impact of acquired thrombotic thrombocytopenic purpura (aTTP).

Condition or disease Intervention/treatment Phase
Acquired Thrombotic Thrombocytopenic Purpura Biological: Caplacizumab Other: Standard of Care Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Follow-up Study for Patients Who Completed Study ALX0681-C301 (HERCULES) to Evaluate Long-term Safety and Efficacy of Caplacizumab (Post-HERCULES)
Actual Study Start Date : October 6, 2016
Actual Primary Completion Date : October 23, 2020
Actual Study Completion Date : October 23, 2020


Arm Intervention/treatment
Experimental: caplacizumab
Participants who completed study ALX0681-C301 (NCT02553317) with standard of care (plasma exchange [PE], corticosteroid and other immunosuppressive agents) or caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product [IMP], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 milligrams (mg) intravenous dose followed by a daily 10 mg subcutaneous injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Biological: Caplacizumab
Other: Standard of Care
• PE with plasma (e.g., fresh frozen plasma, solvent detergent/viral-inactivated plasma, cryosupernatant), • Corticosteroid treatment and • Use of other immunosuppressive agents (e.g., rituximab).




Primary Outcome Measures :
  1. Percentage of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) Related Events [ Time Frame: From Baseline up to 36 months ]
    aTTP-related events were defined as: aTTP-related death, recurrence of aTTP (defined as recurrent thrombocytopenia requiring initiation of daily PE) or at least one major thromboembolic event (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis). Percentage of participants with at least one aTTP-related events during the study were reported in this outcome measure.

  2. Number of Acquired Thrombotic Thrombocytopenic Purpura-related Events [ Time Frame: From Baseline up to 36 months ]
    aTTP-related events were defined as: aTTP-related death, recurrence of aTTP (defined as recurrent thrombocytopenia requiring initiation of daily PE) or at least one major thromboembolic event (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism or deep venous thrombosis).

  3. Time to First Acquired Thrombotic Thrombocytopenic Purpura-related Events [ Time Frame: From Baseline up to 36 months ]
    Time to first aTTP-related events was defined as the duration of time (in days) from Baseline up to first aTTP-related event in LTS16371. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.

  4. Number of Participants With aTTP Related Deaths Reported During the Study [ Time Frame: From Baseline up to 36 months ]
  5. Percentage of Participants With Recurrence of Disease (aTTP) [ Time Frame: From Baseline up to 36 months ]
    Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.

  6. Number of Disease (aTTP) Recurrence Reported During the Study [ Time Frame: From Baseline up to 36 months ]
    Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.

  7. Time to Recurrence of Disease (aTTP) [ Time Frame: From Baseline up to 36 months ]
    Time to first recurrence of disease (aTTP) was defined as the duration of time (in days) from Baseline up to first recurrence of aTTP event in LTS16371. Recurrence of aTTP: defined as recurrent thrombocytopenia requiring initiation of daily PE. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.

  8. Percentage of Participants With Major Thromboembolic Events Including Thrombotic Thrombocytopenic Purpura (TTP) [ Time Frame: From Baseline up to 36 months ]
    Major thromboembolic events (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis) were assessed based on Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). Reported major thromboembolic events included TTP recurrences.

  9. Number of Major Thromboembolic Events Including Thrombotic Thrombocytopenic Purpura [ Time Frame: From Baseline up to 36 months ]
    Major thromboembolic events (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis) were assessed based on SMQ. Reported major thromboembolic events included TTP recurrences.

  10. Time to First Major Thromboembolic Event [ Time Frame: From Baseline up to 36 months ]
    Time to first major thromboembolic event was defined as the duration of time (in days) from Baseline up to first major thromboembolic event in LTS16371. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.

  11. Cognitive Function: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Absolute Scores at Baseline, 36 Months Follow-up Visit, and Change From Baseline in RBANS Total Score at 36 Months Follow-up Visit [ Time Frame: Baseline, 36 Months follow-up visit ]
    The RBANS is a 30-minute comprehensive screening test with five individual domains (immediate memory, delayed memory, attention, language, and visuospatial ability) to examine the cognitive mental status of a participant. Scores from all individual domain were aggregated into a total score and thus RBANS total score ranged from 40 to 160, where higher scores reflected better performance.

  12. Health-Related Quality of Life (HRQoL): Change From Baseline in Headache Impact Test (HIT-6) Total Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    HIT-6 is an easy to administer assessment that was used as a clinical evaluation of the impact of headache on a participant's QoL in both clinical practice and clinical research. The questionnaire included 6 questions covering the 6 areas of functioning most impacted in headache sufferers including pain, role functioning (the ability to carry out usual activities), social functioning, vitality (energy/ fatigue), cognitive functioning, and psychological/emotional distress. Total HIT-6 scores (sum of all individual questions) ranged from 36 (best outcome) to 78 (worst outcome), where higher scores indicated worse condition.

  13. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire (SF-36) Health Survey - Physical Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Physical functioning domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in physical functioning domain score at months 12, 24, and 36 were reported in this outcome measure.

  14. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Physical Domain Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Role Functioning/Physical domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in role functioning/physical domain score at months 12, 24, and 36 were reported in this outcome measure.

  15. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Emotional Domain Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Role functioning/emotional domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in role functioning/emotional domain score at months 12, 24, and 36 were reported in this outcome measure.

  16. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Energy/Fatigue Domain Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Energy/fatigue domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in energy/fatigue domain score at months 12, 24, and 36 were reported in this outcome measure.

  17. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Emotional Well-being Domain Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Emotional well-being domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in emotional well-being domain score at months 12, 24, and 36 were reported in this outcome measure.

  18. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Social Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Social functioning domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in social functioning domain score at months 12, 24, and 36 were reported in this outcome measure.

  19. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Pain Domain Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Pain domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in pain domain score at months 12, 24, and 36 were reported in this outcome measure.

  20. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - General Health Domain Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. General Health domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in general health domain score at months 12, 24, and 36 were reported in this outcome measure.

  21. Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Change in Health Status Scores at Month 12, 24, and 36 Follow-up Visits [ Time Frame: Baseline, Month 12, 24, and 36 Follow-up visits ]
    The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Change in health status scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in change in health status score at months 12, 24, and 36 were reported in this outcome measure.

  22. Percentage of Participants With Drug-induced Treatment-emergent (TE) Anti-drug Antibodies (ADA) Positive Response [ Time Frame: From Baseline up to 36 months ]
    Drug-induced TE ADA positive was based on the outcome of a tiered assay approach that included a modified ADA (mADA) method to eliminate the effects of pre-existing antibodies (pre-Ab). TE ADA responses reported here included both pre-Ab positive and negative responses. A participant was considered as drug-induced TE ADA positive if post-dose samples were positive, regardless of the status of pre-dose samples in the ADA and modified ADA assay.

  23. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Baseline up to 36 months ]
    An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Completed the Final (28 day) follow-up visit in Study ALX0681-C301.
  2. >= 18 years of age at the time of signing the informed consent form.
  3. Provided informed consent prior to initiation of any study specific activity/procedure.

Exclusion Criteria:

  1. Not being able/willing to comply with the study protocol procedures.
  2. Currently enrolled in a clinical study with another investigational drug or device.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02878603


Locations
Show Show 45 study locations
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Medical Director Ablynx, MD Ablynx NV
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] May 24, 2016
Statistical Analysis Plan  [PDF] December 11, 2020

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02878603    
Other Study ID Numbers: LTS16371
2016-001503-23 ( EudraCT Number )
ALX0681-C302 ( Other Identifier: Ablynx )
First Posted: August 25, 2016    Key Record Dates
Results First Posted: November 22, 2021
Last Update Posted: March 28, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Additional relevant MeSH terms:
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Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Thrombophilia