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

Primary Purpose

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

Status

Completed

Phase

Phase 2

Locations

Austria

Study Type

Interventional

Intervention

ARC1779

About this trial

This is an interventional treatment trial for Purpura, Thrombotic Thrombocytopenic

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Archemix Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

TTP Remission Cohort 1

TTP Remission Cohort 2

TTP Remission Cohort 3

Acute TTP Cohort 4

vWD-Type2b Cohort 5

Arm Description

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

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

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

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

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

Full Information

NCT ID

NCT00632242

First Posted

March 3, 2008

Last Updated

January 8, 2009

Sponsor

Archemix Corp.

1. Study Identification

Unique Protocol Identification Number

NCT00632242

Brief Title

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

Official Title

A Phase 2 Pilot Study of the Safety, Pharmacokinetics, and Pharmacodynamics of ARC1779 Injection in Patients With Von Willebrand Factor-Related Platelet Function Disorders

Study Type

Interventional

2. Study Status

Record Verification Date

March 2008

Overall Recruitment Status

Completed

Study Start Date

January 2008 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Archemix Corp.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TTP Remission Cohort 1

Arm Type

Experimental

Arm Description

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

Arm Title

TTP Remission Cohort 2

Arm Type

Experimental

Arm Description

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

Arm Title

TTP Remission Cohort 3

Arm Type

Experimental

Arm Description

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

Arm Title

Acute TTP Cohort 4

Arm Type

Experimental

Arm Description

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

Arm Title

vWD-Type2b Cohort 5

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

ARC1779

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

ARC1779

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

ARC1779

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

ARC1779

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

ARC1779

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

28 days

Secondary Outcome Measure Information:

Title

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

Time Frame

28 days

Title

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

Time Frame

28 days

Title

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

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: 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. 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.

Facility Information:

Facility Name

Archemix Investigational Site

City

Vienna

ZIP/Postal Code

A-1090

Country

Austria

12. IPD Sharing Statement

Citations:

PubMed Identifier

30957581

Citation

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.

Results Reference

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

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