INdividualized ITI Based on Fviii(ATE) Protection by VWF

NCT03204539 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 988465
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief Summary

The primary goal of the INITIATE trial is to compare the clinical outcome of individualized lot selection to random lot selection utilizing one plasma-derived von Willebrand factor (VWF)/coagulation factor (FVIII) complex concentrate for immune tolerance induction (ITI) in subjects with congenital Hemophilia A, FVIII activity ≤2%, and a historical high-titer inhibitor \[≥5 Bethesda Unit (BU)\].

Conditions

Hemophilia A With Inhibitor; Hemophilia A

Keywords

inhibitor; Factor VIII inhibitor

Outcome Measures

Primary Outcomes (1)

• Time to Negative Inhibitor

  This endpoint was chosen because a shorter time to negative inhibitor should decrease monthly break-through bleeding frequency in the early phase of ITI

  completion of immune tolerance induction, up to 18 months

Secondary Outcomes (8)

• Time to Achieve Partial and Complete Success

  completion of immune tolerance induction, up to 18 months

• Absence of Relapse, up to 12 Months After Achievement of Complete or Partial ITI Success

  one year after completion of immune tolerance induction, up to 30 months

• The Number of Break-through Bleeding Events During the Course of ITI-treatment·

  completion of immune tolerance induction, up to 18 months

• Cost of ITI - Including Bleeding Control Using Bypassing Agents Prior to Start and During ITI

  completion of immune tolerance induction, up to 18 months

• Subject Quality of Life

  completion of immune tolerance induction, up to 18 months

Study Arms (2)

Alternative Treatment

EXPERIMENTAL

Half of the participants will be randomized to blinded individualized lot selection for ITI.

Drug: Wilate

Standard Treatment

OTHER

The other half of the participants will receive random lot selection for ITI.

Drug: Wilate

Interventions

Wilate DRUG

Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.

Alternative Treatment; Standard Treatment

Eligibility Criteria

• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of congenital Hemophilia A and baseline FVIII ≤2%.
• Weight ≥ 5 kg
• History of FVIII inhibitor titer ≥5 BU
• Current FVIII inhibitor titer ≥5 BU or ≥0.6 BU and failed ITI defined by FVIII recovery \<66% normal and half-life \<6 hours
• Adequate venous access for daily concentrate infusions
• For participants \<18 years, a parent or guardian willing and able to provide informed consent with verbal or written assent from the child if require by the local institution. For participants ≥18 years, a willingness and ability to provide informed consent from the subject.
• Ability to comply with study related treatments, evaluations, and follow-up.

You may not qualify if:

• Acquired hemophilia
• Congenital or acquired bleeding disorder in addition to Hemophilia A
• ITI factor replacement regimen within the past one month unless there is clear evidence of ITI failure with no reduction in inhibitor titer over the past two months
• HIV positive with viral load ≥200 particles/μL or ≥400,000 copies/mL
• Rituximab within the past 3 months
• IVIG within the past 1 month
• Treatment with other immunosuppressive drugs within the past 1 month (excluding intermittent steroid use for asthma)
• Concomitant experimental treatment
• History of hypersensitivity to plasma-derived VWF- or FVIII-containing concentrates
• Elective surgery planned in the next 6 months (excluding vascular access procedure)
• Any condition or chronic illness, which in the opinion of the investigator makes participation ill-advised
• Inability or unwillingness to complete required screening, follow-up, and exit studies

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (3)

University of California, Davis

Sacramento, California, 95817, United States

Location

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

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: Dr. Jonathan Ducore
• Organization: UC Davis

jmducore@ucdavis.edu

916-734-3461

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: July 2, 2017
• Study Start: June 1, 2017
• Primary Completion: July 19, 2019
• Study Completion: July 19, 2019
• Last Updated: May 29, 2020
• Results First Posted: May 29, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)