Hemophilia A With InhibitorsPhase 4NCT03093480
A Study to Evaluate Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Participants With Inhibitors Undergoing the First ITI Treatment (verITI-8 Study)
A Phase 4 study testing rFVIIIFc in people with Hemophilia A With Inhibitors, run by Bioverativ, a Sanofi company at 37 sites in 10 countries.
Trial summary
The primary purpose of this study was to describe the time to tolerization (i.e., ITI success) with rFVIIIFc in participants within a maximum of 48 weeks (12 months) of ITI treatment. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Hemophilia A With Inhibitors
- What is being tested?
- rFVIIIFc
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 37 sitesin 10 countries
- Study dates
- 8 Dec 2017to 16 Feb 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Ability of the participant or his legally authorized representative (e.g., parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local participant privacy regulations
- Male participants of any age diagnosed with severe hemophilia A (as confirmed from the medical record)
- Currently diagnosed with high titer inhibitors (historical peak greater than or equal to (>=) 5 Bethesda units per milliliter (BU/mL), according to medical records)
- Previously treated with any plasma-derived or recombinant conventional or Extended Half-Life FVIII
Who cannot join
- Other coagulation disorder(s) in addition to hemophilia A
- Previous immune tolerance induction (ITI)
- History of hypersensitivity or anaphylaxis associated with any factor VIII (FVIII) administration
- Planned major surgery scheduled during the study unless deferred until after study completion (minor surgery such as tooth extraction or insertion/replacement of central venous access device is allowed)
- Abnormal renal function (serum creatinine >1.5 milligram per deciliter (mg/dL) or 2 × upper limit of normal (ULN) for participant age based on local laboratory range) as assessed by local laboratory
- Serum alanine aminotransferase or aspartate aminotransferase > 5 × upper limit of normal (ULN) as assessed by local laboratory
Trial locations and contacts
37 sites in 10 countries.
37 sites in 10 countries
United States12 sites
University of Colorado Hemophilia & Thrombosis Center
Aurora, Colorado, 80045
Rush University Medical Center
Chicago, Illinois, 60612
Dayton Children's Hospital
Dayton, Ohio, 45404
Childrens Hospital of Michigan
Detroit, Michigan, 48201
El Paso Children's Hospital
El Paso, Texas, 79905
Cook Children's Medical Center
Fort Worth, Texas, 76104
Gulf States Hemophilia and Thrombophilia Center
Houston, Texas, 77030
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, 46260
University of Iowa Children's Hospital
Iowa City, Iowa, 52242
Blood Center of Southeast Wisconsin
Milwaukee, Wisconsin, 53226
Center for Inherited Blood Disorders
Orange, California, 92868
Children's National Medical Center
Washington D.C., District of Columbia, 20010
France5 sites
CHU Besançon - Hôpital Jean Minjoz
Besançon, Doubs, 25030
Hemostase Clinique - Institut Cœur-Poumons (4eme étage aile est)
Lille, Nord, 59037
Hôpital de la Timone
Marseille, Bouches-Du-Rhône, 13385
Hôpital Necker - Enfants Malades
Paris, 75015
CHU de Toulouse - Hôpital Purpan
Toulouse, Haute Garonne, 31059
Canada3 sites
McMaster Children's Hospital
Hamilton, Ontario, L8N 3Z5
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Children's & Women's Health Centre of British Columbia
Vancouver, British Columbia, V6H 3N1
Italy3 sites
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
Milan, 20122
Azienda Ospedaliera Pediatrica Santobono Pausillipon
Naples, 80122
Ospedale San Bortolo di Vicenza
Vicenza, 36100
Japan3 sites
Nara Medical University Hospital
Kashihara-shi, Nara, 634-8521
St. Marianna University School of Medicine Hospital
Kawasaki, Kanagawa, 216-8511
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8550
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitari i Politecnic La Fe
Valencia, 46026
United Kingdom3 sites
Royal Hospital for Children
Glasgow, Strathclyde, G514TF
St Thomas' Hospital
London, Greater London, SE1 7EH
John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
Belgium2 sites
Cliniques Universitaires Saint-Luc
Brussels, 1200
UZ Leuven
Leuven, 3000
Bulgaria2 sites
UMHAT "Sv. Georgi", EAD
Plovdiv, 4000
UMHAT 'Tsaritsa Yoanna - ISUL', EAD
Sofia, 1527
Germany1 site
Universitaetsklinikum Bonn AoeR
Bonn, North Rhine-Westphalia, 53127
About this study
Official title: A Non-controlled, Open-Label, Multicenter, Study of Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Subjects With Inhibitors Undergoing the First ITI Treatment
The primary purpose of this study was to describe the time to tolerization (i.e., ITI success) with rFVIIIFc in participants within a maximum of 48 weeks (12 months) of ITI treatment.
- Conditions
- Hemophilia A With Inhibitors
- Being tested
- rFVIIIFc
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rFVIIIFcBiological
Also called ELOCTATE/ELOCTA; BIIB031; efmoroctocog alfa; antihemophilic factor [recombinant], Fc fusion protein
rFVIIIFc 200 IU/kg/day in ITI Period, 50 or 100 IU/kg (adjusted according to Investigator judgement) in tapering Period, and prophylactic regimen in Follow-Up period as powder for injection administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Recombinant coagulation factor VIII Fc (rFVIIIFc) | Experimental | Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment. Receives: Biological: rFVIIIFc |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Tolerization With rFVIIIFc
Time required for participants to achieve immune tolerance induction (ITI) success where ITI success is defined as achieving all 3 of the following criteria: confirmed negative titers consisting of 2 consecutive negative inhibitor assessments within 2 weeks (less than [<] 0.6 Bethesda units/milliliter [mL] by the Nijmegen-modified Bethesda assay); incremental recovery (IR) greater than or equal to (>=) 66 percent (%) of the expected IR in 2 consecutive assessments; half-life (t½) >= 7 hours.
Measured: Up to 48 Weeks
Secondary outcomes (11)
Number of Participants With Immune Tolerance Induction (ITI) Success
Number of participants who achieve ITI success where ITI success is defined as achieving all 3 of the following criteria: confirmed negative titers consisting of 2 consecutive negative inhibitor assessments within 2 weeks (<0.6 Bethesda units/mL by the Nijmegen-modified Bethesda assay); incremental recovery (IR) >= 66% of the expected IR at 2 consecutive assessments; half-life (t½) >=7 hours.
Measured: Up to 48 Weeks
Number of Participants Who Experienced Relapse
Number of Participants with ITI success who reaches the criteria for relapse (defined as confirmed positive inhibitor titer >= 0.6 BU/mL or abnormal recovery after tolerance is achieved, and t½ less than [<] 7 hours) evaluated during the Tapering or Follow-Up Periods
Measured: Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)
Annualized Bleeding Rates During ITI Period
A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Annualized bleeding rate for a patient during the ITI period is defined as the number of bleeding episodes divided by the length of the ITI period in days* 365.25.
Measured: Up to 48 weeks
Annualized Bleeding Rates After ITI Period
A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Annualized bleeding rate for a patient after the ITT period (for tapering and follow-up period) is defined as the number of bleeding episodes divided by the length of the period after the ITI period in days* 365.25.
Measured: Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) as a Measure of Safety and Tolerability
An AE is any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition.
Measured: Up to 2 Years
Average Number of Days Missed From Work or School Per Month During ITI Period
Average number of days missed from school or work per month for a period (counting in non-missing diary days) is defined as number of the missing school/work days in the period divided by number of days with data entry in the period.
Number of days per month missed from school or work is reported for those who attend school or have a job.
Measured: Up to 48 weeks
Average Number of Days Missed From Work or School Per Month After ITI Period
Average number of days missed from school or work per month for a period (counting in non-missing diary days) is defined as number of the missing school/work days in the period divided by number of days with data entry in the period.
Number of days per month missed from school or work is reported for those who attend school or have a job.
Measured: Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)
Annualized Number of Hospitalization Days During ITI Period
Annualized number of hospitalization days during a period for a patient is defined as the number of hospitalization days divided by the length of the period in days * 365.25.
Measured: Up to 48 weeks
Annualized Number of Hospitalization Days After ITI Period
Annualized number of hospitalization days during a period for a patient is defined as the number of hospitalization days divided by the length of the period in days * 365.25.
Measured: Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)
Adherence to Treatment Regimen Overall Study Period
Adherence to treatment is based on prescribed daily dose for the overall study period which is defined as the percentage of administered doses versus the prescribed doses to a patient for the entire study duration.
Measured: Up to 2 Years
Annualized rFVIIIFc Consumption for Overall Study Period
Annualized rFVIIIFc consumption for a treatment period is the total nominal rFVIIIFc (IU/kg) / length of period in days * 365.25.
Measured: Up to 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2017
- Study start8 Dec 2017
- Primary completion4 May 2020
- Study completion16 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophilia A With InhibitorsStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bioverativ, a Sanofi company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Swedish Orphan Biovitrum
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03093480
- Sponsor's protocol ID
- LPS16473
- Other IDs
- 2017-000373-36, 997HA402, 2017
- Status last verified
- Mar 2022
- First submitted
- 10 Mar 2017
- Last updated
- 28 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Publications
Malec L, Van Damme A, Chan AKC, Spasova M, Jain N, Sensinger C, Dumont J, Lethagen S, Carcao M, Peyvandi F. Recombinant factor VIII Fc fusion protein for first-time immune tolerance induction: final results of the verITI-8 study. Blood. 2023 Apr 20;141(16):1982-1989. doi: 10.1182/blood.2022017780.
PubMed 36735911
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-controlled, Open-Label, Multicenter, Study of Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Subjects With Inhibitors Undergoing the First ITI Treatment
- ClinicalTrials.gov ID
- NCT03093480
- Acronym / sponsor ID
- LPS16473
- Conditions
- Hemophilia A With Inhibitors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Bioverativ, a Sanofi companyIndustry (pharma, biotech, devices)
- Collaborators
- Swedish Orphan Biovitrum
- Study start
- 8 Dec 2017 (actual)
- Primary completion
- 4 May 2020 (actual)
- Study completion
- 16 Feb 2021 (actual)
- First posted
- 28 Mar 2017 (actual)
- Results
- Posted 7 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study was to describe the time to tolerization (i.e., ITI success) with rFVIIIFc in participants within a maximum of 48 weeks (12 months) of ITI treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recombinant coagulation factor VIII Fc (rFVIIIFc) | Experimental | Biological: rFVIIIFcParticipants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Ability of the participant or his legally authorized representative (e.g., parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local participant privacy regulations
- Male participants of any age diagnosed with severe hemophilia A (as confirmed from the medical record)
- Currently diagnosed with high titer inhibitors (historical peak greater than or equal to (>=) 5 Bethesda units per milliliter (BU/mL), according to medical records)
- Previously treated with any plasma-derived or recombinant conventional or Extended Half-Life FVIII
Key exclusion criteria (6 listed)
- Other coagulation disorder(s) in addition to hemophilia A
- Previous immune tolerance induction (ITI)
- History of hypersensitivity or anaphylaxis associated with any factor VIII (FVIII) administration
- Planned major surgery scheduled during the study unless deferred until after study completion (minor surgery such as tooth extraction or insertion/replacement of central venous access device is allowed)
- Abnormal renal function (serum creatinine >1.5 milligram per deciliter (mg/dL) or 2 × upper limit of normal (ULN) for participant age based on local laboratory range) as assessed by local laboratory
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 |
|---|---|---|
| rFVIIIFcAlso: ELOCTATE/ELOCTA; BIIB031; efmoroctocog alfa; antihemophilic factor [recombinant], Fc fusion proteinrFVIIIFc 200 IU/kg/day in ITI Period, 50 or 100 IU/kg (adjusted according to Investigator judgement) in tapering Period, and prophylactic regimen in Follow-Up period as powder for injection administered intravenously. | Biological | Recombinant coagulation factor VIII Fc (rFVIIIFc) |
Primary outcome
Time to Tolerization With rFVIIIFc
Time frame: Up to 48 Weeks
Time required for participants to achieve immune tolerance induction (ITI) success where ITI success is defined as achieving all 3 of the following criteria: confirmed negative titers consisting of 2 consecutive negative inhibitor assessments within 2 weeks (less than [<] 0.6 Bethesda units/milliliter [mL] by the Nijmegen-modified Bethesda assay); incremental recovery (IR) greater than or equal to (>=) 66 percent (%) of the expected IR in 2 consecutive assessments; half-life (t½) >= 7 hours.
11 secondary outcomes
Number of Participants With Immune Tolerance Induction (ITI) Success
Time frame: Up to 48 Weeks
Number of Participants Who Experienced Relapse
Time frame: Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)
Annualized Bleeding Rates During ITI Period
Time frame: Up to 48 weeks
Annualized Bleeding Rates After ITI Period
Time frame: Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) as a Measure of Safety and Tolerability
Time frame: Up to 2 Years
Average Number of Days Missed From Work or School Per Month During ITI Period
Time frame: Up to 48 weeks
Average Number of Days Missed From Work or School Per Month After ITI Period
Time frame: Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)
Annualized Number of Hospitalization Days During ITI Period
Time frame: Up to 48 weeks
Annualized Number of Hospitalization Days After ITI Period
Time frame: Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)
Adherence to Treatment Regimen Overall Study Period
Time frame: Up to 2 Years
Annualized rFVIIIFc Consumption for Overall Study Period
Time frame: Up to 2 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36735911Malec L, Van Damme A, Chan AKC, Spasova M, Jain N, Sensinger C, Dumont J, Lethagen S, Carcao M, Peyvandi F. Recombinant factor VIII Fc fusion protein for first-time immune tolerance induction: final results of the verITI-8 study. Blood. 2023 Apr 20;141(16):1982-1989. doi: 10.1182/blood.2022017780.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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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.
Clinical Sciences & Operations study director
Sanofi
37 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing rFVIIIFc in people with Hemophilia A With Inhibitors, run by Bioverativ, a Sanofi company at 37 sites in 10 countries.
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 4 inclusion and 6 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: finished, as of the sponsor's last update on 28 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States, France, Canada, Italy, Japan and 5 more countries. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Tolerization With rFVIIIFc (time frame: Up to 48 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03093480, which also lists 1 linked publication.
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 28 Mar 2022.