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

• ClinicalTrials.gov Identifier: NCT03855280
• Recruitment Status: Completed
• First Posted: February 26, 2019
• Last Update Posted: August 31, 2022
• Sponsor: Medexus Pharma, Inc.
• Information provided by (Responsible Party): Medexus Pharma, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hemophilia B	Drug: APVO101	Phase 3

Detailed Description:

Study APVO101-903 is a Phase 3/4, single arm, open-label clinical trial. The purpose of the study is to evaluate pharmacokinetics (PK), safety, and efficacy of APVO101 prophylaxis in severe or moderately severe hemophilia B subjects < 12 years of age. The study is designed to gather information in two age groups of previously treated (with a minimum of 50 previous ED to factor IX replacement therapy) pediatric patients, specifically those < 6 years of age and 6 to <12 years of age.

Study APVO101-903 consists of three distinct phases:

• PK Phase - PK evaluation will consist of administration of a single 75 ± 5 IU/kg dose, followed by factor IX activity and safety assessments up to 50 hours post-infusion.
• Treatment Phase - subjects will receive APVO101 prophylaxis (starting prophylaxis dose to be determined based on APVO101 recovery; ideally within the recommended dose range: 35 - 75 IU/kg; twice weekly) for 50 ED (approximately 6 months).
• Continuation Phase - subjects may continue to receive APVO101 prophylaxis (recommended dose range: 35 - 75 IU/kg; twice weekly) for an additional ≥ 50 ED.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment

Intervention Model Description

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)

• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of a Recombinant Factor IX Product, APVO101, in Previously-Treated Pediatric Patients With Hemophilia B
• Actual Study Start Date: January 16, 2020
• Actual Primary Completion Date: July 4, 2022
• Actual Study Completion Date: July 4, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: APVO101; APVO101: 35 - 75 IU/kg; twice weekly	Drug: APVO101; APVO101: 35 - 75 IU/kg; twice weekly; Other Names: IB1001; Recombinant factor IX; IXINITY

Outcome Measures

Primary Outcome Measures :

1. Annualized Bleed Rate [ Time Frame: 6 Months ]
   Measure assessed during the Treatment Phase

Secondary Outcome Measures :

1. Area under the plasma concentration curve from time 0 to t (AUC0-t) [ Time Frame: Pre-infusion to 50 hours following infusion ]
   Factor IX activity at the following time points post-infusion: 15-30 minutes, 4-6 hours, 24-26 hours and 46-50 hours
2. Terminal Half-life (t 1/2) [ Time Frame: Pre-infusion to 50 hours following infusion ]
   Factor IX activity at the following time points post-infusion: 15-30 minutes, 4-6 hours, 24-26 hours and 46-50 hours
3. Maximum post-infusion plasma concentration (Cmax) [ Time Frame: Pre-infusion to 50 hours following infusion ]
   Factor IX activity at the following time points post-infusion: 15-30 minutes, 4-6 hours, 24-26 hours and 46-50 hours
4. Incremental Recovery [ Time Frame: Pre-infusion to 50 hours following infusion ]
   Factor IX activity at the following time points post-infusion: 15-30 minutes, 4-6 hours, 24-26 hours and 46-50 hours
5. Clearance (CL) [ Time Frame: Pre-infusion to 50 hours following infusion ]
   Factor IX activity at the following time points post-infusion: 15-30 minutes, 4-6 hours, 24-26 hours and 46-50 hours
6. Volume of Distribution at steady-state (V dss) [ Time Frame: Pre-infusion to 50 hours following infusion ]
   Factor IX activity at the following time points post-infusion: 15-30 minutes, 4-6 hours, 24-26 hours and 46-50 hours
7. Degree of Hemorrhage Control [ Time Frame: 6 Months ]

   Subjects rating of bleed control within 6 hours of the time bleeding has stopped:

   Excellent: a dramatic response with abrupt pain relief and clear reduction in joint or hemorrhage site size; Good: pain relief or reduction in hemorrhage site size that may have required an additional infusion for resolution; Fair: probable or slight beneficial response usually requiring one of more additional infusions for resolution; Poor: no improvement or condition worsens.

Eligibility Criteria

• Ages Eligible for Study: up to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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).
2. 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.
3. 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).
4. 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.
5. Subjects must be on prophylaxis or switch to a prophylaxis regimen for the duration of the study.
6. Previously treated patients with a minimum of 50 ED (as documented and determined by the investigator) to a preparation/blood components containing factor IX.
7. 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.
8. Immunocompetent (CD4 count > 400/mm3) and not receiving immune modulating or chemotherapeutic agents.
9. Platelet count at least 150,000/mm3.
10. Liver function: alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2 times the upper limit of the normal range.
11. Total bilirubin ≤ 1.5 times the upper limit of the normal range.
12. Renal function: serum creatinine ≤ 1.25 times the upper limit of the normal range.
13. Hemoglobin ≥ 7 g/dL.

Exclusion Criteria:

1. History of factor IX inhibitor ≥ 0.6 Bethesda Units (BU); confirmed by the screening result.
2. Existence of another coagulation disorder.
3. Evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC).
4. Use of an investigational drug within 30 days prior to study entry.
5. Previous use of APVO101.
6. Use of medications that could impact hemostasis, such as aspirin.
7. Known hypersensitivity to the active substance or to any of the excipients in the investigational products.
8. Known allergic reaction to hamster proteins.
9. 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.
10. 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.
11. History of any medical condition that would impact the efficacy evaluation and/or safety evaluation of the study product.

Contacts and Locations

Locations

Brazil

Centro Estadual de Hemopterapia e Hematologia do Espirito Santo

Vitória, Espirito Santo, Brazil, 29040-090

Universidade Estadual de Campinas - Centro de Hematologia e Hemoterapia

Campinas, Brazil, 13083-878

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

Ribeirão Preto, Brazil, 14051-140

Georgia

JSC K Eristavi National Center for Experimental and Clinical Surgery

Tbilisi, Georgia, 0159

Moldova, Republic of

PMSI Institute of Mother and Child

Chisinau, Moldova, Republic of, MD-2062

South Africa

Worthwhile Clinical Trials, Lakeview Hospital

Benoni, Gauteng, South Africa, 1500

Haemophilia Comprehensive Care Centre

Johannesburg, South Africa, 2193

Turkey

Cukurova University School of Medicine

Adana, Turkey, 01330

Ege University School ofMedicine

İzmir, Turkey, 35100

Ukraine

National Specialized Children's Hospital OKHMATDYT

Kyiv, Ukraine, 01135

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

Lviv, Ukraine, 79044

Sponsors and Collaborators

Medexus Pharma, Inc.

Investigators

• Study Chair: Khaled Mohamed; Medexus Pharma, Inc.

More Information

• Responsible Party: Medexus Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT03855280
• Other Study ID Numbers: APVO101-903
• First Posted: February 26, 2019
• Last Update Posted: August 31, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hemophilia A; Hemophilia B; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked