Evaluation of a Recombinant Factor IX Product, APVO101, in Previously-Treated Pediatric Patients With Hemophilia B

NCT03855280 | Completed Phase 3 Results FDA Drug

• 1 other identifier: APVO101-903
• Study Type: interventional
• Target: 21
• Locations: 6 countries
• Sites: 11

Brief Summary

Phase 3/4, single arm, open-label study to evaluate PK, safety, and efficacy of APVO101 prophylaxis in severe or moderately severe hemophilia B subjects \< 12 years of age.

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (2)

• Annualized Bleeding Rate (ABR)

  The primary efficacy variable was the ABR while on prophylaxis to prevent bleeding episodes. The ABR was defined as the number of bleeding episodes per year.

  Exposure Day 1 up to 50 exposure days (approximately 6 months)

• Annualized Bleeding Rate (ABR) Overall

  The primary efficacy variable was the ABR while on prophylaxis to prevent bleeding episodes. The ABR was defined as the number of bleeding episodes per year.

  Exposure Day 1 through study completion (up to 2.5 years)

Secondary Outcomes (13)

• Concentration (Cmax)

  Pre-infusion to 50 hours post-infusion

• Area Under the Curve (0-inf)

  Pre-infusion to 50 hours post-infusion

• Mean Residence Time (MRT)

  Pre-infusion to 50 hours post-infusion

• Terminal Half-Life (t 1/2)

  Pre-infusion to 50 hours post-infusion

• Clearance (CL)

  Pre-infusion to 50 hours post-infusion

Other Outcomes (8)

• Spontaneous Annualized Bleeding Rate (Treatment Phase)

  Exposure Day 1 up to 50 exposure days (approximately 6 months)

• Spontaneous Annualized Bleeding Rate (Overall)

  Exposure Day 1 through study completion (up to 2.5 years)

• Occurrence of Inhibitory Factor IX Antibodies (Overall)

  Exposure Day 1 through study completion (up to 2.5 years)

Study Arms (1)

APVO101

EXPERIMENTAL

APVO101: 35 - 75 IU/kg; twice weekly

Drug: APVO101

Interventions

APVO101 DRUG

Subjects will receive a single IV dose of APVO101 twice weekly or at a frequency of infusions as determined appropriate by the investigator for the particular study subject for a total of 50 ED. The starting prophylaxis dose will be based on APVO101 recovery from PK Phase assessments (only pre-infusion and 15-30 minute post-infusion samples).

Also known as: IB1001, Recombinant factor IX, IXINITY

APVO101

Eligibility Criteria

• Age: Up to 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age: \< 11.5 years of age at the time of the first dose and \< 12 years throughout the Treatment Phase of the study (for at least 50 ED).
• Informed consent: subject's parent or legal guardian written Institutional Review Board (IRB)/Ethics Committee (EC)-approved informed consent. An assent form (IRB/EC-approved) will be obtained, when required by local regulations/guidelines.
• Willingness and ability to make the required study visits, and follow instructions while enrolled in the study (for at least 50 ED; approximately 6 months).
• Documented severe or moderately severe hemophilia B diagnosis (factor IX activity ≤ 2 IU/dL); in addition, severity may be indicated by the occurrence of one or more joint bleeding episode(s) at any point in the child's medical history requiring infusion(s) to replace factor IX.
• Subjects must be on prophylaxis or switch to a prophylaxis regimen for the duration of the study.
• Previously treated patients with a minimum of 50 ED (as documented and determined by the investigator) to a preparation/blood components containing factor IX.
• Willingness to adhere to the 4-day washout period of any factor IX replacement therapy prior to PK evaluation. In case of previous exposure to a factor IX product with a prolonged half-life, a washout period of 3 half-lives is required in order to achieve steady state factor IX level prior to exposure to APVO101.
• Immunocompetent (CD4 count \> 400/mm3) and not receiving immune modulating or chemotherapeutic agents.
• Platelet count at least 150,000/mm3.
• Liver function: alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2 times the upper limit of the normal range.
• Total bilirubin ≤ 1.5 times the upper limit of the normal range.
• Renal function: serum creatinine ≤ 1.25 times the upper limit of the normal range.
• Hemoglobin ≥ 7 g/dL.

You may not qualify if:

• History of factor IX inhibitor ≥ 0.6 Bethesda Units (BU); confirmed by the screening result.
• Existence of another coagulation disorder.
• Evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC).
• Use of an investigational drug within 30 days prior to study entry.
• Previous use of APVO101.
• Use of medications that could impact hemostasis, such as aspirin.
• Known hypersensitivity to the active substance or to any of the excipients in the investigational products.
• Known allergic reaction to hamster proteins.
• History of poor compliance, geographic isolation, unreliable transportation, a serious medical or social condition, or any other circumstance that, in the opinion of the investigator, would interfere with participation or compliance with the study protocol.
• History of adverse reaction to either plasma-derived factor IX or recombinant factor IX that interfered with the subject's ability to treat bleeding episodes with a factor IX product.
• History of any medical condition that would impact the efficacy evaluation and/or safety evaluation of the study product.

Sponsors & Collaborators

• Medexus Pharma, Inc.: lead

Study Sites (11)

Centro Estadual de Hemopterapia e Hematologia do Espirito Santo

Vitória, Espírito Santo, 29040-090, Brazil

Location

Universidade Estadual de Campinas - Centro de Hematologia e Hemoterapia

Campinas, 13083-878, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirão Preto, 14051-140, Brazil

Location

JSC K Eristavi National Center for Experimental and Clinical Surgery

Tbilisi, 0159, Georgia

Location

PMSI Institute of Mother and Child

Chisinau, MD-2062, Moldova

Location

Worthwhile Clinical Trials, Lakeview Hospital

Benoni, Gauteng, 1500, South Africa

Location

Haemophilia Comprehensive Care Centre

Johannesburg, 2193, South Africa

Location

Cukurova University School of Medicine

Adana, 01330, Turkey (Türkiye)

Location

Ege University School ofMedicine

Izmir, 35100, Turkey (Türkiye)

Location

National Specialized Children's Hospital OKHMATDYT

Kyiv, 01135, Ukraine

Location

State Institute: Institute of Blood Pathology and Transfusion Medicine of the National Academy of Medical Sciences of Ukraine

Lviv, 79044, Ukraine

Location

MeSH Terms

Conditions

Hemophilia B

Interventions

IB1001

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; Genetic Diseases, X-Linked

Results Point of Contact

• Title: Julissa Leon
• Organization: Medexus Pharma

julissa.leon@medexus.com

3125483125

Study Officials

• Khaled Mohamed

  Medexus Pharma, Inc.

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 3/4, single arm, open-label study with three defined phases: * PK Phase: Initial PK evaluation - single dose of APVO101 * Treatment Phase: APVO101 prophylaxis treatment for 50 ED * Continuation Phase: After completion of the Treatment Phase, subjects may continue APVO101 prophylaxis treatment (for an additional ≥ 50 ED)

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: February 26, 2019
• Study Start: January 16, 2020
• Primary Completion: July 4, 2022
• Study Completion: July 4, 2022
• Last Updated: May 16, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (3); GE (1); ZA (2); UA (2); TU (2); MO (1)