ARC1779 Injection in Patients With Von Willebrand Factor-Related Platelet Function Disorders
ARC1779 Injection in Patients With Von Willebrand Factor-Related Platelet Function Disorders
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.
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.
Inclusion Criteria:

 -  Male or female;

 -  Age 18-75 years;

 -  vWD-2b - confirmed diagnosis, or;

 -  TTP Remission - prior episode(s) of primary acute TTP, or;

 -  Acute TTP - any episode, first or relapse, with presence of all of the following:

 1. Microangiopathic hemolytic anemia (schistocytosis present, Coombs test negative);

 2. Severe thrombocytopenia;

 3. Clinical diagnosis of either a primary or secondary form of TTP:(1) Primary TTP:
 e.g., familial TTP (Upshaw-Schulman syndrome), or acquired idiopathic TTP, or
 "atypical HUS"; (2) Secondary TTP: e.g., TTP occurring post-bone marrow
 transplant, drug-induced TTP, lupus-related TTP, etc.;

 -  Negative qualitative urine drug test at screening, and no history of alcohol or drug
 abuse;

 -  Not considering or scheduled to undergo any surgical procedure during the duration of
 the study;

 -  Has not donated or lost more than a unit of blood within 30 days prior to screening
 visit;

 -  Has not received an experimental drug within 30 days prior to screening;

 -  Female patients must be non-pregnant [for TTP Remission and vWD-2b Cohorts, a serum
 pregnancy test at screening and a urine pregnancy test at Day 1 pre-dose must be
 negative; for the Acute TTP Cohort, a serum pregnancy test at Day 1 pre-dose must be
 negative], and willing to use effective, redundant methods of contraception (i.e., for
 both self and male partner) throughout the study and for at least 30 days after
 participation. If possible, the treatment will be initiated within 5 days of the
 cessation of the preceding menstrual period;

 -  Male patients must agree to use a medically acceptable contraceptive (abstinence or
 use of a condom with spermicide) throughout the study and for at least 30 days after
 participation;

 -  Patients must be capable of understanding and complying with the protocol and must
 have signed the informed consent document prior to performance of any study-related
 procedures.

 Exclusion Criteria:

 -  History of recent surgery or trauma;

 -  Any major, active health problem, e.g., cancer or heart disease, which could render
 the patient medically unstable during the period of participation in the study.