ARC1779 Injection in Patients With Von Willebrand Factor-Related Platelet Function Disorders

A Phase 2 Pilot Study of the Safety, Pharmacokinetics, and Pharmacodynamics of 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.