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

NCT00632242 | Completed Phase 2

• 1 other identifier: ARC1779-004
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Purpura, Thrombotic Thrombocytopenic; Von Willebrand Disease Type-2b

Outcome Measures

Primary Outcomes (1)

• To establish the overall safety and tolerability of ARC1779 in three varieties of von Willebrand Factor (vWF)-related platelet function disorders

  28 days

Secondary Outcomes (3)

• To characterize the pharmacokinetic (PK) profile of ARC1779 intravenous (IV) infusion in patient groups

  28 days

• To characterize the pharmacodynamic (PD) profile of ARC1779 in patients with vWF-related platelet function disorders with respect to parameters of platelet function and vWF activity

  28 days

• To assess the concentration- and dose-response relationships among ARC1779 PK and PD parameters.

  28 days

Study Arms (5)

TTP Remission Cohort 1

EXPERIMENTAL

Patients will receive a total dose of 0.47 mg/kg of ARC1779 over 4 hours to achieve a target plasma concentration of 6 mcg/mL

Drug: ARC1779

TTP Remission Cohort 2

EXPERIMENTAL

Patients will receive a total dose of 1.67 mg/kg of ARC1779 over 24 hours to achieve a target plasma concentration of 6 mcg/mL

Drug: ARC1779

TTP Remission Cohort 3

EXPERIMENTAL

Patients will receive a total dose of 3.34 mg/kg of ARC1779 over 24 hours to achieve a target plasma concentration of 12 mcg/mL

Drug: ARC1779

Acute TTP Cohort 4

EXPERIMENTAL

Patients will receive up to a total dose of 40.78 mg/kg of ARC1779 for ≤ 14 days to achieve a target plasma concentration of 12 mcg/mL

Drug: ARC1779

vWD-Type2b Cohort 5

EXPERIMENTAL

Subjects will receive either ARC1779, desmopressin or a combination of ARC1779 and desmopressin in a 3-period crossover design. The maximum dose of ARC1779 will be 0.47 mg/kg to achieve a target plasma concentration of 6 mcg/mL.

Drug: ARC1779

Interventions

ARC1779 DRUG

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.

TTP Remission Cohort 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Microangiopathic hemolytic anemia (schistocytosis present, Coombs test negative);
• Severe thrombocytopenia;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Archemix Corp.: lead

Study Sites (1)

Archemix Investigational Site

Vienna, A-1090, Austria

Location

Related Publications (1)

• Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.

  PMID: 30957581 DERIVED

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

ARC 1779

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 3, 2008
• First Posted: March 10, 2008
• Study Start: January 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: January 9, 2009

Record last verified: 2008-03

Locations

AU (1)