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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-004371-19-AT
• Date of registration: 12/12/2007
• Prospective Registration: No
• Primary sponsor: Archemix Corp.
• Public 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
• Scientific 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
• Date of first enrolment: 20/11/2007
• Target sample size: 28
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004371-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: TPP Cohorts: uncontrolled, open-label If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Austria

Key inclusion & exclusion criteria

Inclusion criteria:
All patients:
• Male or female;
• = 18 to = 75 years of age;
• 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 and Familial 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.

TPP remission patients: History of an episode of acute TTP at any time in the past.

Acute TPP patients:
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:
- Primary TTP: e.g., familial TTP (Upshaw-Schulman syndrome), or acquired idiopathic TTP, or “atypical HUS”;
- Secondary TTP: e.g., TTP occurring post-bone marrow transplant, druginduced TTP, lupus-related TTP, etc.;



vWD-2b patients: Confirmed diagnosis of vWD-2b; Urine pregnancy tests will be repeated in female vWD-2b patients on Day 1 pre-dose for each treatment period.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
All patients:
• History of recent trauma or surgery;
• 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.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

von Willebrand Factor- related platelet function disorders : thrombotic thrombocytopenic purpura(TTP) in remission, acute TTP, and von Willebrand Disease Type- 2b (vWD-2b).
MedDRA version: 9.1 Level: LLT Classification code 10037563 Term: Purpura thrombopenic thrombotic
MedDRA version: 9.1 Level: LLT Classification code 10047715 Term: Von Willebrand's disease

Intervention(s)

Product Name: ARC1779 Injection
Product Code: ARC1779
Pharmaceutical Form: Solution for injection
Current Sponsor code: ARC1779
Other descriptive name: ARC 1779
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: Octostim
Product Name: desmopressin acetate
Product Code: desmopressin acetate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: desmopressin acetate
Current Sponsor code: desmopressin acetate
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: Minirin
Product Name: desmopressin
Product Code: desmopressin
Pharmaceutical Form: Solution for injection
INN or Proposed INN: desmopressin acetate
Current Sponsor code: desmopressin acetate
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Product Name: ARC1779 Injection
Product Code: ARC1779
Pharmaceutical Form: Solution for injection
Current Sponsor code: ARC1779
Other descriptive name: ARC 1779
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): Safety Variables
For all patients, the safety of ARC1779 administration will be assessed through evaluation of the following:
- Adverse events
- Clinical laboratory tests (serum chemistries, urinalysis)
- Coagulation tests (PT, aPTT)
- Hematological profile (blood group typing, complete blood cell count with WBC differential and platelet count)
- Vital signs
- ECG recordings for PR, QRS, and QT intervals and evidence of arrhythmias

Pharmcokinetic variables for all patients receiving ARC1779: Cmax; Tmax; t½ß; t½a, AUCp, AUC0-t, AUC0-last and AUC0-8; ?z; CL, Vss and Vz.
Plasma samples will be analyzed for quantification of ARC1779 concentrations using a validated high performance liquid chromatography (HPLC) method.

Pharmacodynamics:
The PD variables to be measured are: platelet counts, vWF activity (by ELISA directed toward the A1 domain), vWF antigen, vWF multimer gel electrophoresis, shear-dependent platelet function (PFA-100®), shear-dependent platelet adhesion (cone and plate analyzer), and multiplate platelet function analysis.

Main Objective: • To establish the overall safety and tolerability of ARC1779 Injection in patients with
vWF-related platelet function disorders, including patients with TTP in remission,
patients experiencing a current episode of acute TTP, patients with familial TTP
characterized by chronic/recurrent thrombocytopenia, and patients with vWD-2b;
• To characterize the PD profile of ARC1779 Injection in patients with vWF-related
platelet function disorders with respect to parameters of platelet function and vWF
activity;
• To characterize the PK and PD profiles of ARC1779 following SC injection;
• To assess the concentration- and dose-response relationships among ARC1779 PD
and PK parameters.

Secondary Objective:

Secondary ID(s)

ARC1779-004