Alphanate in Immune Tolerance Induction Therapy

NCT03095287 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: GBI14062015-005524-26
• Study Type: interventional
• Target: 2
• Locations: 6 countries
• Sites: 20

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.

Conditions

Hemophilia A, Congenital

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Up to 32.5 months

• Percentage of Participants Who Achieved Complete or Partial Immune Tolerance Without Relapse During the Prophylactic Phase

  12 months during prophylactic phase

• Number of Bleeding Events During ITI Treatment Phase and Prophylactic Phase

  Up to 32.5 months

Other Outcomes (1)

• Treatment-emergent Adverse Events

  Up to 32.5 months

Study Arms (1)

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.

Biological: Alphanate

Interventions

Alphanate BIOLOGICAL

Bolus IV injection.

Also known as: Factor VIII/von Willebrand Factor

Alphanate

Eligibility Criteria

• Age: Up to 12 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead
• Grifols Biologicals, LLC: collaborator

Study Sites (20)

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Childrens Hospital and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

The Childrens Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Robert Wood Johnson Medical Group

New Brunswick, New Jersey, 08901, United States

Location

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

Newark, New Jersey, 07112, United States

Location

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

Chapel Hill, North Carolina, 27517, United States

Location

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

Seattle, Washington, 98101, United States

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N-3Z5, Canada

Location

Lokmanya Tilak Municipal Medical College & General Hospital

Mumbai, Maharashtra, 400022, India

Location

B. J. Govt. Medical College & Sassoon Hospital

Pune, 411001, India

Location

A.O.U. Santa Maria della Misericordia Perugia

Perugia, Umbria, 6132, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Universita degli Studi di Roma La Sapienza

Roma, 00161, Italy

Location

Kemerovo Regional Clinical Hospital

Kemerovo, 650061, Russia

Location

FGUs Hospital - Kirov Scientific Research Institute

Kirov, 610027, Russia

Location

Center for Hemophilia Treatment St.-Petersburg

Saint Petersburg, 191186, Russia

Location

Hospital Universitari i Politecnic La Fe

Valencia, Autonomous Community of Valencia, 46026, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

factor VIII, von Willebrand factor drug combination; von Willebrand Factor

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Results Point of Contact

• Title: Rhonda Griffin
• Organization: Grifols Therapeutics LLC

rhonda.griffin@grifols.com

919-316-6693

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: March 29, 2017
• Study Start: January 3, 2018
• Primary Completion: September 18, 2020
• Study Completion: September 18, 2020
• Last Updated: November 23, 2021
• Results First Posted: November 23, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); IT (3); RU (3); ES (3); CA (1); IN (2)