Hemophilia A With InhibitorPhase 2NCT04592692
A Pharmacokinetic and Clotting Activity Study of FVIII-PEGLip
A Phase 2 study testing PEGylated Liposome (PEGLip) in people with Hemophilia A With Inhibitor, run by Ascension Healthcare Development Limited at 5 sites in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men only
- Conditions the study is for
- Hemophilia A With Inhibitor
- What is being tested?
- PEGylated Liposome (PEGLip)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 5 sitesRussia
- Study dates
- 23 Dec 2019to 31 May 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Russia5 sites, 5 recruiting
- Recruiting
Kemerovo District Clinical Hospital
Kemerovo
Kosinova
- Recruiting
Kirov Scientific Research Institute of Hematology and Blood Transfusion
Kirov
Timofeeva
- Recruiting
National Medical Research Centre of Hematology
Moscow
Zozulia
- Recruiting
Novosibirsk State Medical University, Novosibirsk City Haematology Center
Novosibirsk
Pospelova
- Recruiting
Samara State Medical University
Samara
Kurtov
About this study
Official title: A Pharmacokinetic and Clotting Activity Study of FVIII-PEGLip Administered Intravenously to Severe Haemophilia A Patients With and Without Inhibitors to FVIII
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.
Read the detailed 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.
- Conditions
- Hemophilia A With Inhibitor
- Being tested
- PEGylated Liposome (PEGLip)
- Keywords
- Hemophilia A, Inhibitors
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEGylated Liposome (PEGLip)Drug
Also called Simoctocog alfa
Intravenous co-administration of PEGLip with Simoctocog alfa
| Study group | Role | What they receive |
|---|---|---|
| Inhibitors | Experimental | Patients with inhibitors to FVIII Receives: Drug: PEGylated Liposome (PEGLip) |
| Non-inhibitors | Other | Patients without inhibitors to FVIII Receives: Drug: PEGylated Liposome (PEGLip) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 6 weeks
Bleed frequency
Frequency of spontaneous bleeding episodes and average length (days) of bleeding-free periods
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 4 days
Secondary outcomes (6)
Inhibitor titres
Individual changes of inhibitor titres from baseline measurement to 168 hours after single IV injection of FVIII-PEGLip and at weeks 2, 4, and 6 of 6-week FVIII-PEGLip multiple dosing period
Measured: Approximately 12 weeks
Area under the concentration-time curve (AUC) of PEGLip [single dose]
AUC0-∞ of PEGLip determined at 0 hours (pre-injection) and at 20 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144 and 168 hours after single IV injection of FVIII-PEGLip
Measured: 7 days
Maximum plasma concentration (Cmax) of PEGLip [single dose]
Cmax of PEGLip determined at 0 hours (pre-injection) and at 20 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144 and 168 hours after single IV injection of FVIII-PEGLip
Measured: 7 days
Time to reaching maximum plasma concentration (Tmax) of PEGLip [single dose]
Tmax of PEGLip determined at 0 hours (pre-injection) and at 20 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144 and 168 hours after single IV injection of FVIII-PEGLip
Measured: 7 days
Half-life (t1/2) of PEGLip [single dose]
t1/2 of PEGLip determined at 0 hours (pre-injection) and at 20 min, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144 and 168 hours after single IV injection of FVIII-PEGLip
Measured: 7 days
PEGLip concentration [multiple dose]
PEGLip concentration 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
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start23 Dec 2019
- Primary completion28 Feb 2022 (estimated)
- Study completion31 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia A With InhibitorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascension Healthcare Development Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sam Yurdakul, Study director, Ascension Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04592692
- Sponsor's protocol ID
- CL-SelectAte-II-01
- Status last verified
- Oct 2021
- First submitted
- 21 Sep 2020
- Last updated
- 21 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic and Clotting Activity Study of FVIII-PEGLip Administered Intravenously to Severe Haemophilia A Patients With and Without Inhibitors to FVIII
- ClinicalTrials.gov ID
- NCT04592692
- Acronym / sponsor ID
- CL-SelectAte-II-01
- Conditions
- Hemophilia A With Inhibitor
- Keywords
- Hemophilia A, Inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Ascension Healthcare Development LimitedIndustry (pharma, biotech, devices)
- Study start
- 23 Dec 2019 (actual)
- Primary completion
- 28 Feb 2022 (estimated)
- Study completion
- 31 May 2022 (estimated)
- First posted
- 19 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhibitors | Experimental | Drug: PEGylated Liposome (PEGLip)Patients with inhibitors to FVIII |
| Non-inhibitors | Other | Drug: PEGylated Liposome (PEGLip)Patients without inhibitors to FVIII |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEGylated Liposome (PEGLip)Also: Simoctocog alfaIntravenous co-administration of PEGLip with Simoctocog alfa | Drug | Inhibitors, Non-inhibitors |
Primary outcome
Clotting activity based on ROTEM [single dose]
Time frame: 7 days
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
Clotting activity based on FVIII:C concentration [single dose]
Time frame: 7 days
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
Clotting activity based on ROTEM [multiple dose]
Time frame: 6 weeks
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.
Bleed frequency
Time frame: 6 weeks
Frequency of spontaneous bleeding episodes and average length (days) of bleeding-free periods
Area under the concentration-time curve (AUC) of FVIII:C (FVIII-PEGLip) [single dose]
Time frame: 7 days
AUC0-∞ of FVIII:C after single IV FVIII-PEGLip injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
Area under the concentration-time curve (AUC) of FVIII:C (FVIII-WFI) [single dose]
Time frame: 4 days
AUC0-∞ of FVIII:C after single IV FVIII-WFI injection in severe Haemophilia A patients without inhibitors
Maximum plasma concentration (Cmax) of FVIII:C (FVIII-PEGLip) [single dose]
Time frame: 7 days
Cmax of FVIII:C after single IV FVIII-PEGLip injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
Maximum plasma concentration (Cmax) of FVIII:C (FVIII-WFI) [single dose]
Time frame: 4 days
Cmax of FVIII:C after single IV FVIII-WFI injection in severe Haemophilia A patients without inhibitors
Time to reaching maximum plasma concentration (Tmax) of FVIII:C (FVIII-PEGLip) [single dose]
Time frame: 7 days
Tmax of FVIII:C after single IV FVIII-PEGLip injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
Time to reaching maximum plasma concentration (Tmax) of FVIII:C (FVIII-WFI) [single dose]
Time frame: 4 days
Tmax of FVIII:C after single IV FVIII-WFI injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
Half-life (t1/2) of FVIII:C (FVIII-PEGLip) [single dose]
Time frame: 7 days
T1/2 of FVIII:C after single IV FVIII-PEGLip injection in severe Haemophilia A patients with inhibitors and in patients without inhibitors
Half-life (t1/2) of FVIII:C (FVIII-WFI)
Time frame: 4 days
T1/2 of FVIII:C after single IV FVIII-WFI injection in severe Haemophilia A patients without inhibitors
6 secondary outcomes
Inhibitor titres
Time frame: Approximately 12 weeks
Area under the concentration-time curve (AUC) of PEGLip [single dose]
Time frame: 7 days
Maximum plasma concentration (Cmax) of PEGLip [single dose]
Time frame: 7 days
Time to reaching maximum plasma concentration (Tmax) of PEGLip [single dose]
Time frame: 7 days
Half-life (t1/2) of PEGLip [single dose]
Time frame: 7 days
PEGLip concentration [multiple dose]
Time frame: 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sam Yurdakul study director
Ascension Healthcare
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PEGylated Liposome (PEGLip) in people with Hemophilia A With Inhibitor, run by Ascension Healthcare Development Limited at 5 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sam Yurdakul (+44(0)2072915400, sam.yurdakul@ascension.co.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clotting activity based on ROTEM [single dose] (time frame: 7 days). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2021.