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Trial record 1 of 2 for:    NCT02553317
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Phase III Trial With Caplacizumab in Patients With Acquired Thrombotic Thrombocytopenic Purpura (HERCULES)

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ClinicalTrials.gov Identifier: NCT02553317
Recruitment Status : Completed
First Posted : September 17, 2015
Results First Posted : May 22, 2019
Last Update Posted : May 22, 2019
Sponsor:
Information provided by (Responsible Party):
Ablynx

Study Description
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Brief Summary:
The study was a Phase III, double-blind, placebo-controlled, randomized study to evaluate the efficacy of caplacizumab in more rapidly restoring normal platelet counts as measure of prevention of further microvascular thrombosis

Condition or disease Intervention/treatment Phase
Acquired Thrombotic Thrombocytopenic Purpura Biological: Caplacizumab Biological: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 145 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Double-blind, Randomized, Parallel Group, Multicenter Placebo-controlled Trial to Study the Efficacy and Safety of Caplacizumab in Patients With Acquired Thrombotic Thrombocytopenic Purpura
Actual Study Start Date : November 2015
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Caplacizumab
Caplacizumab 10 mg once daily
 Biological: Caplacizumab
  • First day of treatment: 10 mg intravenous (i.v.) injection prior to plasma exchange (PE) followed by a 10 mg subcutaneous (s.c.) injection (in the abdominal region) after completion of PE on that day.
  • Subsequent days of treatment during PE: daily 10 mg s.c. injection (in the abdominal region) following PE.
  • Treatment after PE period: daily 10 mg s.c. injections for 30 days. If the underlying immunological disease was not resolved, treatment could be extended for a maximum of 4 additional 1-week periods (i.e., 28 days) and was to be accompanied by optimization of immunosuppression.
Other Name: ALX-0081
Placebo Comparator: Placebo
Placebo once daily
 Biological: Placebo
  • First day of treatment: i.v. injection prior to PE followed by a s.c. injection (in the abdominal region) after completion of PE on that day.
  • Subsequent days of treatment during PE: daily s.c. injection (in the abdominal region) following PE.
  • Treatment after PE period: daily s.c. injections for 30 days. If the underlying immunological disease was not resolved, treatment could be extended for a maximum of 4 additional 1-week periods (i.e., 28 days) and was to be accompanied by optimization of immunosuppression.
Other Name: ALX-0081 Placebo


Outcome Measures
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Primary Outcome Measures :
  1. Time to Platelet Count Response [ Time Frame: Only data from the DB daily PE period (median = 5 days) up to the cut-off were used. The cut-off point was defined by whichever occured first: 1) 45 days of daily PE after start of study drug, 2) stop of daily PE, 3) stop of study drug (median = 34 days) ]
    Platelet count response was defined as initial platelet count ≥ 150,000/μL with subsequent stop of daily PE within 5 days. It refers to the first time both conditions, platelet count ≥ 150,000/μL and the stop of daily PE within 5 days, were met.


Secondary Outcome Measures :
  1. Number and Percentage of Subjects With TTP-Related Death, Recurrence of TTP, or a Major Thromboembolic Event During the Study Drug Treatment Period [ Time Frame: The study drug treatment period, a median (min, max) of 36 (2, 82) days. For both treatment groups, only events that occurred prior to a switch to open-label caplacizumab were evaluated for this analysis. ]
    Number and percentage of subjects with TTP-related death, a recurrence of TTP, or at least one treatment-emergent major thromboembolic event during the study drug treatment period (i.e., first key secondary endpoint).

  2. Number and Percentage of Subjects With a Recurrence of TTP in the Overall Study Period [ Time Frame: The overall study period (covers both the overall treatment period and the follow-up period), a median (min, max) of 65 (2, 110) days. ]
    Number and percentage of subjects with a recurrence of TTP during the Overall Study Period (i.e., including follow-up [FU]) (i.e., second key secondary endpoint).

  3. Number and Percentage of Subjects With Refractory Disease [ Time Frame: The study drug treatment period, a median (min, max) of 36 (2, 82) days. ]
    Number and percentage of subjects with refractory TTP, defined as absence of platelet count doubling after 4 days of standard treatment, and lactate dehydrogenase (LDH) > upper limit of normal (ULN) (i.e., third key secondary endpoint).

  4. Time to Normalization of Organ Damage Marker Levels [ Time Frame: Overall study period, a median (min, max) of 65 (2, 110) days. For both treatment groups, normalizations occurring during the open-label period were not evaluated in this analysis. ]

    Time to first normalization of LDH, cardiac troponin I (cTnI) and serum creatinine was defined as: first time of LDH ≤ ULN and cTnI ≤ ULN and serum creatinine ≤ ULN - time of first i.v. loading dose of study drug after randomization + 1 minute. Subjects in either initial treatment group who switched to open-label caplacizumab before having reached the endpoint were censored at time of switch.

    Of note, the key secondary endpoints were hierarchically ordered to allow statistical testing for these endpoints at the same nominal significance level of 5% without adjustment, as long as the tests occurred in the pre-defined sequential order, and given that all null hypotheses tested for endpoints with a higher rank (including the primary endpoint) were rejected. No confirmatory testing was done for this fourth key secondary endpoint, as the statistical test was not significant for the proportion of subjects with refractory disease (i.e., the third key secondary endpoint).



Other Outcome Measures:
  1. Number of Days of Plasma Exchange [ Time Frame: Overall study drug treatment period, a median (min, max) of 36 (2, 82) days. ]
    The number of days of PE during the overall study drug treatment period, including the number of days of PE during the open-label study drug treatment period. Data were analyzed according to the initial treatment allocation (both before and after switch to open-label caplacizumab).

  2. Total Volume of Plasma Exchange [ Time Frame: Overall study drug treatment period, a median (min, max) of 36 (2, 82) days. ]
    The total volume of PE during the overall study drug treatment period, including the total volume of PE during the open-label study drug treatment period. Data were analyzed according to the initial treatment allocation (both before and after switch to open-label caplacizumab).

  3. Number of Days in Intensive Care Unit [ Time Frame: Overall study drug treatment period, a median (min, max) of 36 (2, 82) days. ]
    The number of days in intensive care unit (ICU) during the overall study drug treatment period, including the number of days in ICU during the open-label study drug treatment period. Data were analyzed according to the initial treatment allocation (both before and after switch to open-label caplacizumab).

  4. Number of Days in Hospital [ Time Frame: Overall study drug treatment period, a median (min, max) of 36 (2, 82) days. ]
    The number of days in hospital during the overall study drug treatment period, including the number of days in hospital during the open-label study drug treatment period. Data were analyzed according to the initial treatment allocation (both before and after switch to open-label caplacizumab).


Eligibility Criteria
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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. Adult male or female ≥ 18 years of age at the time of signing the informed consent form (ICF).
  2. Clinical diagnosis of acquired thrombotic thrombocytopenic purpura (aTTP) (initial or recurrent), which included thrombocytopenia and microscopic evidence of red blood cell fragmentation (e.g., schistocytes).
  3. Required initiation of daily PE treatment and had received 1 PE treatment prior to randomization
  4. Others as defined in the protocol

Exclusion Criteria:

  1. Platelet count ≥100×10E9/L.
  2. Serum creatinine level >200 µmol/L in case platelet count is > 30×10E9/L
  3. Known other causes of thrombocytopenia
  4. Congenital TTP (known at the time of study entry).
  5. Pregnancy or breast-feeding.
  6. Subjects who were previously enrolled in a clinical study with caplacizumab and received caplacizumab or for whom the assigned treatment arm is unknown
  7. Others as defined in the protocol
Contacts and Locations
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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): NCT02553317


Locations
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Sponsors and Collaborators
Ablynx
Investigators
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Study Director: Medical Monitor Ablynx NV
  Study Documents (Full-Text)

Documents provided by Ablynx:
Study Protocol  [PDF] July 20, 2016
Statistical Analysis Plan  [PDF] September 14, 2017

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Ablynx
ClinicalTrials.gov Identifier: NCT02553317    
Other Study ID Numbers: ALX0681-C301
2015-001098-42 ( EudraCT Number )
First Posted: September 17, 2015    Key Record Dates
Results First Posted: May 22, 2019
Last Update Posted: May 22, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
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