Brief 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.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

participants targeted

Target at below P25 for phase_2

Timeline

Completed

Started Dec 2019

Geographic Reach

1 country

5 active sites

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.4 years study duration

Study Start

First participant enrolled

December 23, 2019

Completed

9 months until next milestone

First Submitted

Initial submission to the registry

September 21, 2020

Completed

28 days until next milestone

First Posted

Study publicly available on registry

October 19, 2020

Completed

1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2022

Completed

3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2022

Completed

Last Updated

October 21, 2021

Status Verified

October 1, 2021

Enrollment Period

2.2 years

First QC Date

September 21, 2020

Last Update Submit

October 20, 2021

Conditions

Hemophilia A With Inhibitor

Keywords

Hemophilia AInhibitors

Outcome Measures

Primary Outcomes (12)

Clotting activity based on ROTEM [single dose]
Clotting profile of single IV injection of FVIII-PEGLip based on key ROTEM parameters (CT+CFT) determined at 0 hours (pre-injection) and at 20 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144 and 168 hours after injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
7 days
Clotting activity based on FVIII:C concentration [single dose]
Clotting profile of single IV injection of FVIII-PEGLip based on FVIII:C plasma assay measured at 0 hours (pre-injection) and at 20 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144 and 168 hours after injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
7 days
Clotting activity based on ROTEM [multiple dose]
Dynamics of blood clotting activity as quantified by key ROTEM parameters (CT+CFT) measured before and 20 minutes after each injection of FVIII-PEGLip at weeks 2, 4 and 6 of 6-week multiple dosing of FVIII-PEGLip in severe Haemophilia A patients with inhibitors and patients without inhibitors.
6 weeks
Bleed frequency
Frequency of spontaneous bleeding episodes and average length (days) of bleeding-free periods
6 weeks
Area under the concentration-time curve (AUC) of FVIII:C (FVIII-PEGLip) [single dose]
AUC0-∞ of FVIII:C after single IV FVIII-PEGLip injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
7 days
Area under the concentration-time curve (AUC) of FVIII:C (FVIII-WFI) [single dose]
AUC0-∞ of FVIII:C after single IV FVIII-WFI injection in severe Haemophilia A patients without inhibitors
4 days
Maximum plasma concentration (Cmax) of FVIII:C (FVIII-PEGLip) [single dose]
Cmax of FVIII:C after single IV FVIII-PEGLip injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
7 days
Maximum plasma concentration (Cmax) of FVIII:C (FVIII-WFI) [single dose]
Cmax of FVIII:C after single IV FVIII-WFI injection in severe Haemophilia A patients without inhibitors
4 days
Time to reaching maximum plasma concentration (Tmax) of FVIII:C (FVIII-PEGLip) [single dose]
Tmax of FVIII:C after single IV FVIII-PEGLip injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
7 days
Time to reaching maximum plasma concentration (Tmax) of FVIII:C (FVIII-WFI) [single dose]
Tmax of FVIII:C after single IV FVIII-WFI injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
4 days
Half-life (t1/2) of FVIII:C (FVIII-PEGLip) [single dose]
T1/2 of FVIII:C after single IV FVIII-PEGLip injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
7 days
Half-life (t1/2) of FVIII:C (FVIII-WFI)
T1/2 of FVIII:C after single IV FVIII-WFI injection in severe Haemophilia A patients without inhibitors
4 days

Secondary Outcomes (6)

Inhibitor titres
Approximately 12 weeks
Area under the concentration-time curve (AUC) of PEGLip [single dose]
7 days
Maximum plasma concentration (Cmax) of PEGLip [single dose]
7 days
Time to reaching maximum plasma concentration (Tmax) of PEGLip [single dose]
7 days
Half-life (t1/2) of PEGLip [single dose]
7 days
+1 more secondary outcomes

Other Outcomes (1)

Adverse events
Approximately 12 weeks

Study Arms (2)

Inhibitors

EXPERIMENTAL

Patients with inhibitors to FVIII

Drug: PEGylated Liposome (PEGLip)

Non-inhibitors

OTHER

Patients without inhibitors to FVIII

Drug: PEGylated Liposome (PEGLip)

Interventions

PEGylated Liposome (PEGLip)DRUG

Intravenous co-administration of PEGLip with Simoctocog alfa

Also known as: Simoctocog alfa

InhibitorsNon-inhibitors

Eligibility Criteria

Age18 Years - 60 Years

Sexmale(Gender-based eligibility)

Gender Eligibility DetailsMale patients only

Healthy VolunteersNo

Age GroupsAdult (18-64)

You may qualify if:

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/μL 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.

You may not qualify if:

Low platelet counts (\<100000 / μl);
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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Ascension Healthcare Development Limitedlead

Study Sites (5)

Kemerovo District Clinical Hospital

Kemerovo, Russia

RECRUITING

Kirov Scientific Research Institute of Hematology and Blood Transfusion

Kirov, Russia

RECRUITING

National Medical Research Centre of Hematology

Moscow, Russia

RECRUITING

Novosibirsk State Medical University, Novosibirsk City Haematology Center

Novosibirsk, Russia

RECRUITING

Samara State Medical University

Samara, Russia

RECRUITING

MeSH Terms

Conditions

Hemophilia A

Interventions

simoctocog alfa (Nuwiq)

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, InheritedBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesCoagulation Protein DisordersHemorrhagic DisordersGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

Sam Yurdakul
Ascension Healthcare
STUDY DIRECTOR

Central Study Contacts

Sam Yurdakul

CONTACT

+44(0)2072915400 sam.yurdakul@ascension.co.uk

Study Design

Study Type: interventional
Phase: phase 2
Allocation: NON RANDOMIZED
Masking: NONE
Purpose: TREATMENT
Intervention Model: PARALLEL
Sponsor Type: INDUSTRY
Responsible Party: SPONSOR

Study Record Dates

First Submitted

September 21, 2020

First Posted

October 19, 2020

Study Start

December 23, 2019

Primary Completion

February 28, 2022

Study Completion

May 31, 2022

Last Updated

October 21, 2021

Record last verified: 2021-10

Data Sharing

IPD Sharing: Will not share

Locations

RU(5)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (12)

Secondary Outcomes (6)

Other Outcomes (1)

Study Arms (2)

Inhibitors

Non-inhibitors

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (5)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Study Officials

Central Study Contacts

Study Design

Study Record Dates

Data Sharing

Locations