Study to Assess Efficacy and Safety of Anti-von Willebrand Factor (vWF) Nanobody in Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Condition: Acquired Thrombotic Thrombocytopenic Purpura
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic
Intervention: Caplacizumab; Placebo
Intervention description: Subjects received a first intravenous (i.v.) bolus of 10 mg (filled at 5 mg/mL) caplacizumab via push injection within 6 hours to 15 minutes prior to the first PE on study. The first PE on study could either be the very first PE session for the current episode of aTTP (if the subject was randomized prior to the initiation of PE) or the second PE session (if the subject was randomized after a single PE session).
The first PE on study was followed by subcutaneous (s.c.) administration of 10 mg study drug within 30 minutes after the end of the PE procedure.
All subsequent study drug administrations were daily s.c. injections within 30 minutes after the end of the PE procedure (if applicable) or within 24 hours of the previous dose.
Subjects received caplacizumab up to 30 days after the last PE session.; Subjects received a first i.v. bolus of placebo via push injection within 6 hours to 15 minutes prior to the first PE on study. The first PE on study could either be the very first PE session for the current episode of aTTP (if the subject was randomized prior to the initiation of PE) or the second PE session (if the subject was randomized after a single PE session).
The first PE on study was followed by s.c. administration of placebo within 30 minutes after the end of the PE procedure.
All subsequent study drug administrations were daily s.c. injections within 30 minutes after the end of the PE procedure (if applicable) or within 24 hours of the previous dose.
Subjects received placebo up to 30 days after the last PE session.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Masking description: A single-blinded study design was initiated because, in the initial versions of the protocol, the dosing regimen could be adjusted dependent on the results of the Ristocetin Cofactor (RICO) test following the initial dose. Therefore, a double-blind design was not feasible because the results of the RICO test effectively unblinded the Investigator. Single-blind design was maintained due to the objective nature of the primary endpoint.
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study was a Phase II, single-blind, randomized, placebo-controlled trial to determine
      whether anti-vWF Nanobody is safe and effective as adjunctive treatment in patients with
      aTTP.

      Patients received either placebo or anti-vWF Nanobody as adjunctive therapy to plasma
      exchange (PE).
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years of age or older (adults) or aged 12 to < 18 years (adolescents)

          -  Male or female subject, willing to accept an acceptable contraceptive regimen

          -  Subject with a clinical diagnosis of TTP

          -  Requiring PE (one single PE session prior to randomization into the study was allowed)

          -  Subject accessible to follow-up

          -  Subject able to provide signed and dated informed consent and assent (if applicable,
             for adolescents)

        Exclusion Criteria:

          -  Platelet count ≥ 100,000/µL

          -  Severe active infection indicated by sepsis (requirement for pressors with or without
             positive blood cultures)

          -  Clinical evidence of enteric infection with Escherichia coli 0157 or related organism

          -  Anti-phospholipid syndrome

          -  Diagnosis of disseminated intravascular coagulation (DIC)

          -  Pregnancy or breast-feeding

          -  Hematopoietic stem cell or bone marrow transplantation-associated thrombotic
             microangiopathy

          -  Known with congenital TTP

          -  Active bleeding or high risk of bleeding

          -  Uncontrolled arterial hypertension

          -  Known chronic treatment with anticoagulant treatment that cannot be stopped safely,
             including but not limited to:

               -  vitamin K antagonists

               -  heparin or low molecular weight heparin (LMWH)

               -  non-acetyl salicylic acid non-steroidal anti-inflammatory molecules

          -  Severe or life threatening clinical condition other than TTP that would impair
             participation in the study

          -  Subjects with malignancies resulting in a life expectation of less than 3 months

          -  Subjects with known or suspected bone marrow carcinosis

          -  Subjects who cannot comply with study protocol requirements and procedures

          -  Known hypersensitivity to the active substance or to excipients of the study drug

          -  Severe liver impairment, corresponding to grade 3 toxicity defined by the CTCAE scale.
             For the key liver parameters, this is defined as follows:

               -  bilirubin > 3 x upper limit of normal (ULN) (needed to differentiate isolated
                  increase in indirect bilirubin due to hemolysis, this was not an exclusion
                  parameter but disease-related)

               -  alanine transaminase (ALT)/ aspartate transaminase (AST) > 5 x ULN

               -  alkaline phosphatase (ALP) > 5 x ULN

               -  gamma-glutamyl transpeptidase (GGT) > 5 x ULN

          -  Severe chronic renal impairment, as defined by glomerular filtration rate < 30 mL/min

        Note that the use of another investigational drug or device within 30 days prior to
        screening was not allowed. Participation in non-interventional/observational studies and
        registries during the study period was allowed. Participation in another clinical study was
        not allowed until the end of the follow-up period or within 30 days after the last study
        treatment in case of early subject withdrawal from the study. Subjects who had already
        participated in the current study and had either completed the study per protocol or had
        discontinued prematurely, were not allowed to be re-included.