NCT03103542|CompletedPhase 4ResultsFDA Drug

Study of rFVIIIFc for Immune Tolerance Induction (ITI) in Haemophilia A Patients With Inhibitors Who Have Failed Previous ITI Therapies

ReITIrate

A Non-Controlled, Open-Label, Multicenter, Study of Immune Tolerance Induction Performed With rFVIIIFc Within a Timeframe of 60 Weeks in Severe Haemophilia A Patients With Inhibitors Who Have Failed Previous Immune Tolerance Induction Therapies

Swedish Orphan Biovitrum ClinicalTrials.gov

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2 other identifiers

Sobi.Elocta-0032017-000065-73

Study Type

interventional

Target

Locations

7 countries

Sites

Timeline

RegisteredApr 2017

StartedAug 2017

CompletionAug 2020

Brief Summary

The primary purpose of this study is to describe the outcome of Immune Tolerance Induction (ITI) treatment performed with rFVIIIFc within a timeframe of 60 weeks in patients with haemophilia A who have failed previous attempts at tolerization.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_4

Timeline

Completed

Started Aug 2017

Typical duration for phase_4

Geographic Reach

7 countries

12 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3 years study duration

First Submitted

Initial submission to the registry

March 31, 2017

Completed

6 days until next milestone

First Posted

Study publicly available on registry

April 6, 2017

Completed

5 months until next milestone

Study Start

First participant enrolled

August 29, 2017

Completed

2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 4, 2019

Completed

12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2020

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

November 30, 2021

Completed

Last Updated

September 19, 2024

Status Verified

September 1, 2024

Enrollment Period

2 years

First QC Date

March 31, 2017

Results QC Date

August 3, 2021

Last Update Submit

September 17, 2024

Conditions

Hemophilia A

Keywords

ITIrFVIIIFcImmune Tolerance Induction

Outcome Measures

Primary Outcomes (1)

ITI Success
Number of patients who achieve ITI success where ITI success is defined as achieving all 3 of the following criteria: * Negative titer for inhibitor (\<0.6 Bethesda units/mL by the Nijmegen-modified Bethesda assay) at 2 consecutive visits * FVIII incremental recovery (IR) \>66% of the expected IR at 2 consecutive visits * FVIII half-life (t½) ≥7 hours
up to 60 weeks

Secondary Outcomes (11)

Time to ITI Success
up to 60 weeks
Occurrence of Relapse During a 48-week Period Following Successful ITI Treatment
Up to 48 weeks
Number of Bleedings During ITI Treatment
up to 60 weeks
Bleeding Rate During a 48-week Period Following Successful ITI Treatment
up to 48 weeks
Adverse Events (AEs)
SAEs - approx 166 weeks AEs - approx 110 weeks
+6 more secondary outcomes

Study Arms (1)

Recombinant coagulation factor VIII Fc (rFVIIIFc)

EXPERIMENTAL

Participants will 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 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc.

Biological: Recombinant coagulation factor (rFVIIIFc)

Interventions

Recombinant coagulation factor (rFVIIIFc)BIOLOGICAL

rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.

Also known as: ELOCTA, ELOCTATE

Recombinant coagulation factor VIII Fc (rFVIIIFc)

Eligibility Criteria

Sexmale

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

Signed and dated informed consent provided by the patient, or the patient's legally authorized representative for patients under the legal age. Assent should be obtained from pediatric patients according to local regulations
Male patients of any age diagnosed with severe haemophilia A, as confirmed from the medical record
Previously treated with any plasma-derived or recombinant conventional or extended half-life FVIII
Diagnosed with high titer inhibitors (historical peak ≥5 Bethesda units (BU)/mL according to medical records)
Inhibitor titer \>0.6 BU at screening
Failed previous ITI attempt(s) with any plasma-derived or recombinant conventional or extended half-life FVIII including the use of immunosuppressant The attempt should be documented in the medical records and have the following characteristics:
A minimum FVIII dose equivalent to the low dose arm of the International ITI study (50 IU/kg, 3 times/week)
A minimum ITI treatment period of 33 months or
Shorter than 33 months if no downward trend of at least 20% in the inhibitor titer in a 6-month period after the initial 3 months of the ITI treatment
All patients must practice effective contraception during the study and for 3 months after their last dose of study treatment

You may not qualify if:

Other coagulation disorder(s) in addition to haemophilia A
History of hypersensitivity reactions associated with any rFVIIIFc administration
High risk of cardiovascular, cerebrovascular, or other thromboembolic events, as judged by the investigator
Planned major surgery to be deferred after study completion. Minor surgery such as tooth extraction or insertion/replacement of central venous access device is allowed.
Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to screening. Exceptions to this include: ribavirin for treatment of Hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days within 12 weeks prior to Day 1) and/or inhaled steroids
Abnormal renal function (serum creatinine \>2.0 mg/dL) as assessed by local lab
Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>5 × upper limit of normal (ULN) as assessed by local lab
Serum total bilirubin \>3 × ULN as assessed by local lab
Cluster of differentiation 4 (CD4) lymphocytes ≤200 mm3 if known as HIV antibody positive at Screening
Viral load of ≥400 copies/mL if known HIV antibody positive at Screening
Patients with a documented history of alcohol or substance abuse within 12 months prior to randomization
Participation in another concurrent clinical interventional study within 30 days of screening or intake of an investigational drug within five half-lives of that investigational drug has passed
Foreseeable inability to cooperate with given instructions or study procedures

Contact the study team to confirm eligibility.