Hemophilia A, CongenitalPhase 2NCT03095287
Alphanate in Immune Tolerance Induction Therapy
A Phase 2 study testing Alphanate in people with Hemophilia A, Congenital, run by Grifols Therapeutics LLC at 20 sites in 6 countries.
Trial summary
This is a multicenter, multinational, prospective, single-arm, nonrandomized, open-label study, planned in of approximately 25 male participants with congenital hemophilia A who will receive their first (primary) immune tolerance induction (ITI) treatment with alphanate. Read more about this study
- Who is it for?
- Ages Up to 12 years, men only
- Conditions the study is for
- Hemophilia A, Congenital
- What is being tested?
- Alphanate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 20 sitesin 6 countries
- Study dates
- 3 Jan 2018to 18 Sep 2020
- Phase
- Phase 2
- 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 Up to 12 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- The subject has a documented diagnosis of severe congenital hemophilia A with FVIII:C <1% of normal.
- The subject is a male <12 years (and at least 2 years of age if in India) at the Baseline Visit.
- The subject's documented historical peak inhibitor titer is ≥5 BU and ≤200 BU.
- The subject has an inhibitor titer >0.6 BU and <10 BU at Screening.
- The subject has had a delay ≤24 months from the date of diagnosis of the inhibitor to the start of the subject's ITI treatment.
Who cannot join
- The subject has acquired factor VIII (FVIII) deficiency.
- The subject has previously received ITI treatment.
- The subject has a recent (within 1 month) history of central line infection at the time of Screening.
- The subject has a high risk of cardiovascular, cerebrovascular, or thromboembolic event as judged by the investigator.
- The subject is currently undergoing treatment with immunosuppressive drugs (eg, systemic corticosteroids), azathioprine, cyclophosphamide, high dose immunoglobulin, interferon, or the use of a protein A column or plasmapheresis and is unwilling to discontinue these treatments starting at the screening visit.
- The subject has a known infection with human immunodeficiency virus (HIV) or has clinical signs and symptoms consistent with current HIV infection.
Show all 11Show fewer
- The subject has a known previous infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) or has clinical signs and symptoms consistent with current HBV or HCV infection.
- The subject has significant proteinuria, has a history of acute renal failure or severe renal impairment (blood urea nitrogen or creatinine >2 times the upper limit of normal), or is receiving dialysis at Screening.
- The subject has a value of aspartate transaminase or alanine aminotransferase >2 times the upper limit of normal at Screening.
- The subject has clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the trial or place the subject at undue medical risk.
- The subject has a history of anaphylaxis or severe systemic reaction to any plasma derived or other blood products.
Trial locations and contacts
20 sites in 6 countries.
20 sites in 6 countries
United States8 sites
Emory University
Atlanta, Georgia, 30322
University of North Carolina at Chapel Hill, Hemophilia and Thrombosis Center
Chapel Hill, North Carolina, 27517
The Childrens Mercy Hospital
Kansas City, Missouri, 64108
University of Kentucky
Lexington, Kentucky, 40536
Childrens Hospital and Clinics of Minnesota
Minneapolis, Minnesota, 55404
Robert Wood Johnson Medical Group
New Brunswick, New Jersey, 08901
Newark Beth Israel Medical Center & Children's Hospital of New Jersey
Newark, New Jersey, 07112
Seattle Children's Hospital, Seattle Children's Research Institute
Seattle, Washington, 98101
Italy3 sites
Azienda Ospedaliera Universitaria Careggi
Florence, 50134
A.O.U. Santa Maria della Misericordia Perugia
Perugia, Umbria, 6132
Universita degli Studi di Roma La Sapienza
Roma, 00161
Russia3 sites
Kemerovo Regional Clinical Hospital
Kemerovo, 650061
FGUs Hospital - Kirov Scientific Research Institute
Kirov, 610027
Center for Hemophilia Treatment St.-Petersburg
Saint Petersburg, 191186
Spain3 sites
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Universitari i Politecnic La Fe
Valencia, Autonomous Community of Valencia, 46026
India2 sites
Lokmanya Tilak Municipal Medical College & General Hospital
Mumbai, Maharashtra, 400022
B. J. Govt. Medical College & Sassoon Hospital
Pune, 411001
About this study
Official title: A Multicenter Phase 2 Open-Label, Single-Arm, Prospective, Interventional Study of Plasma-Derived Factor VIII/VWF (Alphanate®) in Immune Tolerance Induction Therapy in Subjects With Congenital Hemophilia A
This is a multicenter, multinational, prospective, single-arm, nonrandomized, open-label study, planned in of approximately 25 male participants with congenital hemophilia A who will receive their first (primary) immune tolerance induction (ITI) treatment with alphanate.
The study consists of 2 phases:
- An ITI Treatment Phase in which all eligible participants will receive ITI treatment with alphanate for a period of up to 33 months. Upon confirmation of complete immune tolerization, participants will then enter a 12-month Prophylactic Phase. If, after 33 months of ITI, a participants has achieved partial immune tolerance, the participants will enter a 12-month Prophylactic Phase.
- A 12-month Prophylactic Phase for all participants who meet the criteria for complete or partial success to continue on a prophylactic dosing regimen of alphanate. Due to limited enrollment, this study was early terminated.
Read the detailed description
Male participants <12 years of age with an inhibitor titer >0.6 to <10 Bethesda Units (BU) will be screened before the planned start of ITI treatment. Participants continuing to meet the entrance criteria will enter the ITI Treatment Phase and receive daily doses of alphanate 100 IU/kg/day for up to 33 months, with a one-time option to increase to a dosing regimen of 200 IU/kg/day at any time after 90 days of ITI treatment.
Participants will continue to receive their daily alphanate dose for up to 33 months until the titer is negative (<0.6 BU) on 2 consecutive assessments and treatment success is confirmed by FVIII:C pharmacokinetic assessments, at which time they will enter the 12-month Prophylactic Phase.
In addition, participants who have achieved partial immune tolerance at the completion of 33 months of ITI treatment will enter the 12-month Prophylactic Phase. Participants who do not achieve partial immune tolerance at the completion of 33 months of ITI treatment will be discontinued as treatment failures.
The Prophylactic Phase begins with an 8-week taper period for participants tolerized with 100 IU/kg/day or with a 12-week taper period for participants tolerized with 200 IU/kg/day to bring the dose down in a step-wise manner to a prophylactic dose of alphanate 50 IU/kg every other day or 3 times per week, at the investigator's discretion. During the Prophylactic Phase, participants will be monitored monthly for the first 4 months and then every 2 months for the remaining 8 months to assess sustainability of immune tolerance. Due to limited enrollment, this study was early terminated.
- Conditions
- Hemophilia A, Congenital
- Being tested
- Alphanate
- Keywords
- Factor VIII, von Willebrand Factor, Plasma-derived, Inhibitors, Immune tolerance induction (ITI), Antibodies, Hemophilia A
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlphanateBiological
Also called Factor VIII/von Willebrand Factor
Bolus IV injection.
| Study group | Role | What they receive |
|---|---|---|
| Alphanate | Experimental | Participants were to receive alphanate 100 International Units (IU/kg/day) for up to 33 months in Immune tolerance induction (ITI) Treatment Phase. The dose could be increased up to 200 IU/kg/day based on Investigator's discretion. Following ITI Treatment Phase, participants were to enter the Prophylactic Phase where alphanate dose was to be tapered down in a step wise manner to reach a final prophylactic dose of 50 IU/kg every other day or 3 times per week, at the investigator's discretion. Receives: Biological: Alphanate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Achieved Complete Immune Tolerance Within 33 Months of Initiation of Immune Tolerance Induction (ITI) Treatment Phase
Complete immune tolerance was defined as the participants achieving 2 consecutive undetectable inhibitor titers (<0.6 BU) performed within 2 weeks of each other, Factor VIII activity (FVIII:C) in vivo plasma recovery ≥66% of the predicted normal value and FVIII:C half-life ≥6 hours after a 72-hour FVIII treatment-free period.
Measured: Up to 32.5 months
Secondary outcomes (3)
Percentage of Participants Who Achieved Either Complete or Partial Immune Tolerance Within 33 Months of Initiation of ITI Treatment Phase
Complete immune tolerance was defined as the participants achieving 2 consecutive undetectable inhibitor titers (<0.6 BU) performed within 2 weeks of each other, Factor VIII activity (FVIII:C) in vivo plasma recovery ≥66% of the predicted normal value and FVIII:C half-life ≥6 hours after a 72-hour FVIII treatment-free period. Partial immune tolerance was defined as participants achieving reduction of inhibitor titer to <5 BU confirmed at 2 consecutive assessments within 2 weeks of each other, FVIII:C in vivo plasma recovery of <66% of the predicted normal value or FVIII:C half-life of <6 hours after a 72-hour FVIII treatment-free period and clinical response to FVIII therapy.
Measured: Up to 32.5 months
Percentage of Participants Who Achieved Complete or Partial Immune Tolerance Without Relapse During the Prophylactic Phase
Relapse during the prophylactic phase for participants who have achieved complete immune tolerance was defined as a return of FVIII inhibitor titer to detectable levels (≥0.6 BU) or FVIII:C recovery <66% of the predicted normal value or FVIII:C half-life <6 hours, confirmed by repeat assessment within approximately 2 weeks. Relapse for participants who have achieved partial immune tolerance was defined as an increase of FVIII inhibitor titer to ≥5 BU, confirmed by repeat assessment within approximately 2 weeks.
Measured: 12 months during prophylactic phase
Number of Bleeding Events During ITI Treatment Phase and Prophylactic Phase
Annualized frequencies of bleeding events during the ITI Treatment Phase and the Prophylactic Phase
Measured: Up to 32.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2017
- Study start3 Jan 2018
- Primary completion18 Sep 2020
- Study completion18 Sep 2020
Why it stopped: Terminated due to limited enrollment (non-safety related decision)
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.
- Other trials for Hemophilia A, CongenitalStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grifols Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Grifols Biologicals, LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03095287
- Sponsor's protocol ID
- GBI1406
- Other IDs
- 2015-005524-26, 2015
- Status last verified
- Oct 2021
- First submitted
- 23 Mar 2017
- Last updated
- 23 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 2 Open-Label, Single-Arm, Prospective, Interventional Study of Plasma-Derived Factor VIII/VWF (Alphanate®) in Immune Tolerance Induction Therapy in Subjects With Congenital Hemophilia A
- ClinicalTrials.gov ID
- NCT03095287
- Acronym / sponsor ID
- GBI1406
- Conditions
- Hemophilia A, Congenital
- Keywords
- Factor VIII, von Willebrand Factor, Plasma-derived, Inhibitors, Immune tolerance induction (ITI), Antibodies, Hemophilia A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to limited enrollment (non-safety related decision)
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Grifols Therapeutics LLCIndustry (pharma, biotech, devices)
- Collaborators
- Grifols Biologicals, LLC
- Study start
- 3 Jan 2018 (actual)
- Primary completion
- 18 Sep 2020 (actual)
- Study completion
- 18 Sep 2020 (actual)
- First posted
- 29 Mar 2017 (actual)
- Results
- Posted 23 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, multinational, prospective, single-arm, nonrandomized, open-label study, planned in of approximately 25 male participants with congenital hemophilia A who will receive their first (primary) immune tolerance induction (ITI) treatment with alphanate.
The study consists of 2 phases:
- An ITI Treatment Phase in which all eligible participants will receive ITI treatment with alphanate for a period of up to 33 months. Upon confirmation of complete immune tolerization, participants will then enter a 12-month Prophylactic Phase. If, after 33 months of ITI, a participants has achieved partial immune tolerance, the participants will enter a 12-month Prophylactic Phase.
- A 12-month Prophylactic Phase for all participants who meet the criteria for complete or partial success to continue on a prophylactic dosing regimen of alphanate. Due to limited enrollment, this study was early terminated.
Detailed description
Male participants <12 years of age with an inhibitor titer >0.6 to <10 Bethesda Units (BU) will be screened before the planned start of ITI treatment. Participants continuing to meet the entrance criteria will enter the ITI Treatment Phase and receive daily doses of alphanate 100 IU/kg/day for up to 33 months, with a one-time option to increase to a dosing regimen of 200 IU/kg/day at any time after 90 days of ITI treatment.
Participants will continue to receive their daily alphanate dose for up to 33 months until the titer is negative (<0.6 BU) on 2 consecutive assessments and treatment success is confirmed by FVIII:C pharmacokinetic assessments, at which time they will enter the 12-month Prophylactic Phase.
In addition, participants who have achieved partial immune tolerance at the completion of 33 months of ITI treatment will enter the 12-month Prophylactic Phase. Participants who do not achieve partial immune tolerance at the completion of 33 months of ITI treatment will be discontinued as treatment failures.
The Prophylactic Phase begins with an 8-week taper period for participants tolerized with 100 IU/kg/day or with a 12-week taper period for participants tolerized with 200 IU/kg/day to bring the dose down in a step-wise manner to a prophylactic dose of alphanate 50 IU/kg every other day or 3 times per week, at the investigator's discretion. During the Prophylactic Phase, participants will be monitored monthly for the first 4 months and then every 2 months for the remaining 8 months to assess sustainability of immune tolerance. Due to limited enrollment, this study was early terminated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alphanate | Experimental | Biological: AlphanateParticipants were to receive alphanate 100 International Units (IU/kg/day) for up to 33 months in Immune tolerance induction (ITI) Treatment Phase. The dose could be increased up to 200 IU/kg/day based on Investigator's discretion. Following ITI Treatment Phase, participants were to enter the Prophylactic Phase where alphanate dose was to be tapered down in a step wise manner to reach a final prophylactic dose of 50 IU/kg every other day or 3 times per week, at the investigator's discretion. |
Who may qualify
- Ages
- Up to 12 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- The subject has a documented diagnosis of severe congenital hemophilia A with FVIII:C <1% of normal.
- The subject is a male <12 years (and at least 2 years of age if in India) at the Baseline Visit.
- The subject's documented historical peak inhibitor titer is ≥5 BU and ≤200 BU.
- The subject has an inhibitor titer >0.6 BU and <10 BU at Screening.
- The subject has had a delay ≤24 months from the date of diagnosis of the inhibitor to the start of the subject's ITI treatment.
Key exclusion criteria (11 listed)
- The subject has acquired factor VIII (FVIII) deficiency.
- The subject has previously received ITI treatment.
- The subject has a recent (within 1 month) history of central line infection at the time of Screening.
- The subject has a high risk of cardiovascular, cerebrovascular, or thromboembolic event as judged by the investigator.
- The subject is currently undergoing treatment with immunosuppressive drugs (eg, systemic corticosteroids), azathioprine, cyclophosphamide, high dose immunoglobulin, interferon, or the use of a protein A column or plasmapheresis and is unwilling to discontinue these treatments starting at the screening visit.
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 |
|---|---|---|
| AlphanateAlso: Factor VIII/von Willebrand FactorBolus IV injection. | Biological | Alphanate |
Primary outcome
Percentage of Participants Who Achieved Complete Immune Tolerance Within 33 Months of Initiation of Immune Tolerance Induction (ITI) Treatment Phase
Time frame: Up to 32.5 months
Complete immune tolerance was defined as the participants achieving 2 consecutive undetectable inhibitor titers (<0.6 BU) performed within 2 weeks of each other, Factor VIII activity (FVIII:C) in vivo plasma recovery ≥66% of the predicted normal value and FVIII:C half-life ≥6 hours after a 72-hour FVIII treatment-free period.
3 secondary outcomes
Percentage of Participants Who Achieved Either Complete or Partial Immune Tolerance Within 33 Months of Initiation of ITI Treatment Phase
Time frame: Up to 32.5 months
Percentage of Participants Who Achieved Complete or Partial Immune Tolerance Without Relapse During the Prophylactic Phase
Time frame: 12 months during prophylactic phase
Number of Bleeding Events During ITI Treatment Phase and Prophylactic Phase
Time frame: Up to 32.5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alphanate in people with Hemophilia A, Congenital, run by Grifols Therapeutics LLC at 20 sites in 6 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 5 inclusion and 11 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: stopped early, as of the sponsor's last update on 23 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Italy, Russia, Spain, India and 1 more country. 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?
Yes. Results are posted in the registry (first posted 23 Nov 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?
Percentage of Participants Who Achieved Complete Immune Tolerance Within 33 Months of Initiation of Immune Tolerance Induction (ITI) Treatment Phase (time frame: Up to 32.5 months). 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 23 Nov 2021.