Study on the Dose-response Relationship of Pharmacodynamic Parameters in Patients With Hemophilia With Inhibitors

NCT04789954 | Completed Early Phase 1

• 1 other identifier: UGA 2020-01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, double-blind, single-dose, 5 ways crossover, exploratory clinical trial evaluating four different doses of AryoSeven (eptacog alfa, activated) and NovoSeven on selected pharmacodynamic parameters in patients with hemophilia with inhibitors.

Conditions

Hemophilia A With Inhibitor; Hemophilia B With Inhibitor

Outcome Measures

Primary Outcomes (1)

• Lag time of the thrombin generation curve

  Time to 16.7% of peak plasmatic concentration, in minutes.

  Up to 30 hours after AryoSeven and NovoSeven injection

Secondary Outcomes (8)

• Endogenous Thrombin Potential (PD parameter)

  Up to 30 hours after AryoSeven and NovoSeven injection

• Time to Peak (PD parameter)

  Up to 30 hours after AryoSeven and NovoSeven injection

• Peak height (PD parameter)

  Up to 30 hours after AryoSeven and NovoSeven injection

• F1.2 prothrombin fragments (PD parameter)

  Up to 30 hours after AryoSeven and NovoSeven injection

• D-dimer (PD parameter)

  Up to 30 hours after AryoSeven and NovoSeven injection

Study Arms (5)

AryoSeven 10 μg/kg

EXPERIMENTAL

Single dose, intravenously

Biological: Eptacog alfa, activated

AryoSeven 30 μg/kg

EXPERIMENTAL

Single dose, intravenously

Biological: Eptacog alfa, activated

AryoSeven 90 μg/kg

EXPERIMENTAL

Single dose, intravenously

Biological: Eptacog alfa, activated

AryoSeven 270 μg/kg

EXPERIMENTAL

Single dose, intravenously

Biological: Eptacog alfa, activated

NovoSeven 30 μg/kg

ACTIVE COMPARATOR

Single dose, intravenously

Biological: Eptacog alfa, activated

Interventions

Eptacog alfa, activated BIOLOGICAL

A dose sequence for each injection will be randomly selected from the following doses: 10 μg/kg, 30 μg/kg, 90 μg/kg, or 270 μg/kg, separated by a wash-out period of 3 days.

AryoSeven 10 μg/kg; AryoSeven 270 μg/kg; AryoSeven 30 μg/kg; AryoSeven 90 μg/kg; NovoSeven 30 μg/kg

Eligibility Criteria

• Age: 12 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of congenital haemophilia A or B with inhibitors to FVIII or FIX titer \>5 Bethesda Units \[BU\]
• with \> 2 episodes of bleeding/year requiring treatment with FVII infusions, not in bleeding episode
• Male adults and adolescents (\>12 years)
• Patient informed consent has been obtained \[Patients to be enrolled must also provide voluntary written informed consent to the protocol prior to screening to be eligible for the study. For adolescents, parent/legal guardian must provide consent and, wherever possible, patient assent will also be obtained. For compromised patients, their designated proxy must provide informed consent\].
• Patients willing and able to be hospitalized prior to time of study medication administration for plasma sampling (5 times during the study).

You may not qualify if:

• Any other type of congenital or acquired coagulopathy, such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy.
• Antibodies against Factor VII
• Ongoing bleeding prophylaxis regimens with AryoSeven/NovoSeven or planned to occur during the trial
• Platelet count less than 100.000 platelets/mcL (at screening visit)
• Any clinical sign or known history of arterial thrombotic event or deep venous- thrombosis or pulmonary embolism
• HIV positive with current CD4+ count of less than 200/µL
• Liver cirrhosis
• Factor VIII/IX immune tolerance induction regimen planned to occur during the trial
• Known hypersensitivity to the study medication
• Parallel participation in another experimental drug trial.
• Parallel participation in another marketed drug trial that may affect the primary end-point of the study.

Sponsors & Collaborators

• AryoGen Pharmed Co.: lead

Study Sites (1)

Comprehensive Hemophilia Care Center

Tehran, Iran

Location

MeSH Terms

Interventions

Factor VII

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Massimo Iacobelli, MD

  Consultant

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 10, 2021
• Study Start: December 29, 2020
• Primary Completion: August 13, 2021
• Study Completion: July 31, 2022
• Last Updated: September 10, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)