ARC1779 Injection in Patients With Von Willebrand Factor-Related Platelet Function Disorders
Condition: Purpura, Thrombotic Thrombocytopenic; Von Willebrand Disease Type-2b
MeSH terms: Purpura; Von Willebrand Diseases; Purpura, Thrombotic Thrombocytopenic; Von Willebrand Disease, Type 2
Study type: Interventional
Phase: Phase 2

Summary: 
      To evaluate the overall safety and tolerability of ARC1779, a therapeutic oligonucleotide
      ("aptamer") in patients with three types of von Willebrand Factor related platelet disorders.
    

Detailed description: 
      ARC1779 Injection will be investigated in 4 cohorts of TTP patients as an uncontrolled,
      open-label study. Patients with vWD-2b will be enrolled in an additional cohort in a
      randomized, blinded, double-dummy, and placebo-controlled study.

      Collectively, patients representing 3 different vWF-related platelet function disorders: TTP
      in remission, acute TTP, and vWD-2b will be treated in a total of 5 cohorts. Three cohorts
      will consist of patients who are status post an episode of TTP ("TTP Remission Cohorts") and
      will be treated with ARC1779 Injection in a dose- and duration-escalation design. In
      parallel, a single cohort of patients with acute TTP ("Acute TTP Cohort") will be treated
      according to an individual patient titration-to-response paradigm. This cohort will be opened
      for enrollment at the beginning of the study and closed after all of the other cohorts are
      completed. Also in parallel, a single cohort of patients with vWD-2b ("vWD-2b Cohort") will
      begin enrollment at the commencement of the study and continue independently of the course of
      the TTP Remission Cohorts. Up to 4 patients will be included in each of the TTP cohorts. The
      vWD-2b Cohort is expected to consist of up to 12 vWD-2b patients.
    

Intervention name(s): ARC1779; ARC1779; ARC1779; ARC1779; ARC1779
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Initial stepwise infusion of 0.23 mg/kg given over 30 minutes and subsequent continuous infusion of an additional 0.24 mg/kg given over 4 hours at a rate of 0.001 mg/kg/min.; Initial stepwise infusion of 0.23 mg/kg given over 30 minutes and subsequent continuous infusion of an additional 1.44 mg/kg given over 24 hours at a rate of 0.001 mg/kg/min.; Initial stepwise infusion of 0.46 mg/kg over 30 minutes and subsequent continuous infusion of an additional 2.88 mg/kg given over 24 hours at a rate of 0.002 mg/kg/min.; Initial stepwise infusion of 0.23 mg/kg given over 30 minutes and subsequent continuous infusion of an additional 1.44 mg/kg given over 24 hours at a rate of 0.001 mg/kg/min to produce a target plasma concentration of 6 mcg/mL.
Continuous infusion of ARC1779 Injection may continue for ≤ 14 days. After initial 24 hours dose may be titrated to achieve a target plasma concentration of 12 mcg/mL as needed, on the basis of clinical and laboratory data, according to the Investigator's judgment.; In one period of the sequence, ARC1779 will be administered to all subjects as a stepwise infusion of 0.23 mg/kg over 30 minutes and subsequent continuous infusion of an additional 0.24 mg/kg given over 4 hours at a rate of 0.001 mg/kg/min in combination with a dummy 30-minute infusion of placebo. In another period, subjects will receive a single infusion of desmopressin at a dose of 0.4 mcg/kg given over 30 minutes in combination with a dummy 30-minute stepwise infusion followed by 4-hour continuous infusion of placebo. In the one other period, subjects will receive the combination of desmopressin at a dose of 0.4 mcg/kg given over 30 minutes and ARC1779 given as a stepwise infusion of 0.23 mg/kg over 30 minutes and subsequent continuous infusion of an additional 0.24 mg/kg given over 4 hours at a rate of 0.001 mg/kg/min
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment