A Pharmacokinetic and Clotting Activity Study of FVIII-PEGLip

  • STATUS
    Recruiting
  • End date
    May 31, 2022
  • participants needed
    20
  • sponsor
    Ascension Healthcare Development Limited
Updated on 28 October 2021

Summary

The purpose of this study is to demonstrate that PEGylated liposomes (PEGLip) can shield FVIII from the immune system and inhibitors, and therefore provide a prophylactic FVIII replacement therapy for patients with inhibitors to FVIII.

Description

This is an open-label multicenter trial for patients with severe haemophilia A with inhibitors to FVIII and without inhibitors as control. The trial consists of 4 periods: Screening, Stage A, Stage B and Safety Follow-up.

After signing informed consent, patients are assessed for eligibility during a Screening period lasting up to 21 days.

All eligible patients enter Stage A - Regimen estimation. The non-inhibitor patients receive a single IV injection at a dose of 35 IU/kg FVIII reconstituted with Water For Injection. Following a 4-day wash-out period, these patients as well as patients with inhibitors receive a single IV injection of FVIII-PEGLip at a dose of 35 IU/kg FVIII + PEGLip 22 mg/kg to determine the duration of haemostatic cover and therefore required injection frequency to prevent bleeds.

Stage B - multiple dosing: all patients receive injections of FVIII-PEGLip for 6 weeks at a frequency determined in Stage A for each individual patient.

Safety follow-up: 15 and 30 days after the last injection of FVIII-PEGLip, patients are contacted for any adverse events or bleeding episodes.

Details
Condition Hemophilia A With Inhibitor
Treatment PEGylated Liposome (PEGLip)
Clinical Study IdentifierNCT04592692
SponsorAscension Healthcare Development Limited
Last Modified on28 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male adult patients aged 18 to 60 years
Severe Haemophilia A (FVIII plasma level <1IU/dL) with documented history of bleeds (for at least 6 months prior to enrolment)
For patients without inhibitors: inhibitor titre < 0,6 Bethesda units and no medi-cal history of inhibitors
For patients with inhibitors: inhibitor titre 0,6 Bethesda units or documented medical history of inhibitors titre 0,6 Bethesda units
Adequate hematologic function, defined as platelet count 100,000/L and hemoglobin 8 g/dL ( 4.97 mmol/L) at the time of screening
Adequate hepatic function, defined as total bilirubin 1.5 the upper limit of normal (ULN) (excluding Gilbert's syndrome) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 3 ULN at the time of screening; no clinical signs or known laboratory/radiographic evidence consistent with cirrho-sis
Adequate renal function, defined as serum creatinine 2.5 ULN and creati-nine clearance by Cockcroft-Gault formula 30 mL/min
Patient's written informed consent, confirming his willingness to comply with the requirements of this protocol

Exclusion Criteria

Low platelet counts (<100000 / l)
Congenital or acquired bleeding defects (including acquired hemophilia) other than Hemophilia A
Abnormal renal function (serum creatinine concentrations greater than 1.3 mg/dL)
Active hepatic disease (persistent aspartate aminotransferase [AST] or alanine aminotransferase [ALT] increases to greater than five times the upper limit of normal)
A history of severe adverse reactions to blood products and/or plasma derived FVIII concentrates or liposomes, or PEG, or Nuwiq
A history of allergic reactions to bypassing agents
Any concomitant immunological disease (e.g. autoimmune chronic active hepati-tis, autoimmune thrombocytopenic purpura or Immune Thrombocytopenic Pur-pura (ITP), lupus, Multiple Sclerosis (MS))
Patients receiving immunosuppressive treatment (excluding glucocorticoids)
Patients receiving therapy with interferon
Patients receiving any immune tolerance induction (ITI) therapy at the moment of the screening
Any individual with known dyslipidemia disease or actively taking cholesterol lowering drugs for the treatment of hypercholesterolemia or hyperlipidemia (e.g., statins, cholesterol absorption inhibitors, bile acid sequestrates, nicotinic acid or fibrates)
Intake of NSAIDs (except COX-2 inhibitors), acetylsalicylic acid (Aspirin) or any other antiplatelet agents, opioids
Patients who have participated in another Clinical Trial (including medical device studies) within the past 60 days
Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient's safe participation in and completion of the study or interpretation of the study results, according to the Investigator
For patients without inhibitors - a history of demonstrating long half-lives for FVIII
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note