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

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ClinicalTrials.gov Identifier: NCT03855280
Recruitment Status : Not yet recruiting
First Posted : February 26, 2019
Last Update Posted : November 5, 2019
Sponsor:
Information provided by (Responsible Party):
Aptevo Therapeutics

Tracking Information
First Submitted Date  ICMJE February 25, 2019
First Posted Date  ICMJE February 26, 2019
Last Update Posted Date November 5, 2019
Estimated Study Start Date  ICMJE November 15, 2019
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2019)
Annualized Bleed Rate [ Time Frame: 6 Months ]
Measure assessed during the Treatment Phase
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03855280 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of a Recombinant Factor IX Product, APVO101, in Previously-Treated Pediatric Patients With Hemophilia B
Official Title  ICMJE Evaluation of a Recombinant Factor IX Product, APVO101, in Previously-Treated Pediatric Patients With Hemophilia B
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.
Detailed Description

Study APVO101-903 is a Phase 3/4, single arm, open-label clinical trial. The purpose of the study is to evaluate 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Hemophilia B
Intervention  ICMJE Drug: APVO101
APVO101: 35 - 75 IU/kg; twice weekly
Other Names:
  • IB1001
  • Recombinant factor IX
  • IXINITY
Study Arms  ICMJE Experimental: APVO101
Intervention: Drug: APVO101
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 25, 2019)
22
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2021
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David Schaaf, MD 206-859-6655 schaafd@apvo.com
Contact: Julissa Leon 206-838-0513 leonj@apvo.com
Listed Location Countries  ICMJE Colombia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03855280
Other Study ID Numbers  ICMJE APVO101-903
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Aptevo Therapeutics
Study Sponsor  ICMJE Aptevo Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: David Schaaf, MD Aptevo Therapeutics
PRS Account Aptevo Therapeutics
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP