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Completed

NCT Number: NCT02553317

Phase III Trial With Caplacizumab in Patients With Acquired Thrombotic Thrombocytopenic Purpura

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

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Key information

Conditions

Acquired Thrombotic Thrombocytopenic Purpura Blood Coagulation Disorders Blood Platelet Disorders Cytopenia Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhage Pathologic Processes Pathological Conditions, Signs and Symptoms Purpura Purpura, Thrombocytopenic Purpura, Thrombotic Thrombocytopenic Signs and Symptoms Skin Manifestations Thrombocytopenia Thrombophilia Thrombotic Microangiopathies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Investigator Site, Brisbane, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult male or female ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • 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).
  • Required initiation of daily PE treatment and had received 1 PE treatment prior to randomization
  • Others as defined in the protocol

Exclusion criteria

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

Treatment and study plan

Caplacizumab

Biological
  • 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 names: ALX-0081

Placebo

Biological
  • 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 names: ALX-0081 Placebo

Primary outcomes

  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 outcomes

  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 outcomes

  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).

Sponsors and collaborators

Lead sponsor

Ablynx, a Sanofi company

Industry

Registry information

Official study 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

Acronym: HERCULES

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Sep 17, 2015
Registry last updated
Apr 5, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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