Alphanate in Immune Tolerance Induction Therapy

NCT ID: NCT03095287

Last Updated: 2021-11-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-03
• Study Completion Date: 2020-09-18

Brief 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.

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.

Conditions

Hemophilia A, Congenital

Keywords

Factor VIII; von Willebrand Factor; Plasma-derived; Inhibitors; Immune tolerance induction (ITI); Antibodies; Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Alphanate

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.

Group Type: EXPERIMENTAL

Alphanate

Intervention Type: BIOLOGICAL

Bolus IV injection.

Interventions

Alphanate

Bolus IV injection.

Intervention Type: BIOLOGICAL

Other Intervention Names

Factor VIII/von Willebrand Factor

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.

• Maximum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Grifols Biologicals, LLC

INDUSTRY

Sponsor Role: collaborator

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Emory University

Atlanta, Georgia, United States

University of Kentucky

Lexington, Kentucky, United States

Childrens Hospital and Clinics of Minnesota

Minneapolis, Minnesota, United States

The Childrens Mercy Hospital

Kansas City, Missouri, United States

Robert Wood Johnson Medical Group

New Brunswick, New Jersey, United States

Newark Beth Israel Medical Center & Children's Hospital of New Jersey

Newark, New Jersey, United States

University of North Carolina at Chapel Hill, Hemophilia and Thrombosis Center

Chapel Hill, North Carolina, United States

Seattle Children's Hospital, Seattle Children's Research Institute

Seattle, Washington, United States

McMaster Children's Hospital

Hamilton, Ontario, Canada

Lokmanya Tilak Municipal Medical College & General Hospital

Mumbai, Maharashtra, India

B. J. Govt. Medical College & Sassoon Hospital

Pune, , India

A.O.U. Santa Maria della Misericordia Perugia

Perugia, Umbria, Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Universita degli Studi di Roma La Sapienza

Roma, , Italy

Kemerovo Regional Clinical Hospital

Kemerovo, , Russia

FGUs Hospital - Kirov Scientific Research Institute

Kirov, , Russia

Center for Hemophilia Treatment St.-Petersburg

Saint Petersburg, , Russia

Hospital Universitari i Politecnic La Fe

Valencia, Autonomous Community of Valencia, Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Countries

United States; Canada; India; Italy; Russia; Spain

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-005524-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GBI1406

Identifier Type: -

Identifier Source: org_study_id