Study to Assess Efficacy and Safety of Anti-von Willebrand Factor Nanobody in Patients With Acquired Thrombotic Thrombocytopenic Purpura (TTP) (TITAN)

• Reduction of number of relapses [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Number of patients relapsing of TTP (de novo event of TTP that occurs later than 30 days after the last daily plasma exchange) for a maximum of 1 year, and time to first relapse of TTP
• Reduction of number of exacerbations [ Time Frame: 30 days after the last daily plasma exchange session ] [ Designated as safety issue: No ]
  Number of exacerbations of TTP, and time to first exacerbation of TTP

• Reduction of number of relapses [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Number of patients relapsing of TTP (de novo event of TTP that occurs later than 30 days after the last plasma exchange) for a maximum of 1 year, and time to first relapse of TTP
• Reduction of number of exacerbations [ Time Frame: 30 days after the last plasma exchange session ] [ Designated as safety issue: No ]
  Number of exacerbations of TTP, and time to first exacerbation of TTP

The purpose of this study is to determine whether anti-von Willebrand factor Nanobody is safe and effective as adjunctive treatment in patients with acquired thrombotic thrombocytopenic purpura (TTP). Patients will receive either placebo or anti-von Willebrand factor Nanobody as adjunctive therapy to plasma exchange.

• Biological: anti-vWF Nanobody
  10 mg i.v. bolus injection prior to plasma exchange, followed by 10 mg s.c. injection once or twice per day. Maximum treatment duration is limited to 90 days.
• Biological: Placebo
  10 mg i.v. bolus injection prior to plasma exchange, followed by daily 10 mg s.c. injection. Maximum treatment duration is limited to 90 days.

• Experimental: anti-vWF Nanobody
  Intervention: Biological: anti-vWF Nanobody
• Placebo Comparator: Placebo
  Intervention: Biological: Placebo

Inclusion Criteria:

• 18 years of age or older
• Men or women willing to accept an acceptable contraceptive regimen
• Patients with clinical diagnosis of TTP
• Necessitating plasma exchange
• Patient accessible to follow-up
• Obtained, signed and dated informed consent

Exclusion Criteria:

• Platelet count greater or equal to 100,000/µL
• Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures)
• Clinical evidence of enteric infection with E.coli 0157 or related organism
• Anti-phospholipid syndrome
• Diagnosis of disseminated intravascular coagulation (DIC)
• Pregnancy or breast-feeding
• Haematopoietic stem cell or bone marrow transplantation-associated thrombotic microangiopathy
• Known congenital TTP
• Active bleeding or high risk of bleeding
• Uncontrolled arterial hypertension
• Known chronic treatment with anticoagulant treatment that can not be stopped safely
• Severe or life threatening clinical condition other than TTP that would impair participation in the trial
• 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 (common terminology criteria for adverse events) scale
• Severe chronic renal impairment