Trial of AAV5-hFIX in Severe or Moderately Severe Hemophilia B

NCT02396342 | Completed Phase 1 Results DMC

• 1 other identifier: CT-AMT-060-01
• Study Type: interventional
• Target: 10
• Locations: 3 countries
• Sites: 7

Brief Summary

This study evaluates how safe gene therapy treatment with AAV5-hFIX is in adult patients with severe or moderately severe hemophilia B and severe bleeding type.

Conditions

Hemophilia B

Keywords

Hemophilia B, gene therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  From AMT-060 infusion through end of study (5 years post-dose)

Secondary Outcomes (11)

• FIX-replacement-therapy-free FIX Activity

  From AMT-060 infusion through end of study (5 years post-dose)

• Total Annualized Bleeding Rate (ABR)

  From AMT-060 infusion through end of study (5 years post-dose)

• Total Consumption of FIX Replacement Therapy

  From AMT-060 infusion through end of study (5 years post dose).

• Change From Baseline in Short Form-36 (SF-36) Quality of Life (QoL) Scores

  From AMT-060 infusion through the end of study (5 years post dose)

• Time to Vector DNA Stopped Shedding From Blood, Nasal Secretions, Saliva, Urine, Feces, and Semen

  From AMT-060 infusion through end of study (5 years post dose).

Study Arms (2)

Cohort 1

EXPERIMENTAL

AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion

Genetic: AAV5-hFIX

Cohort 2

EXPERIMENTAL

AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion

Genetic: AAV5-hFIX

Interventions

AAV5-hFIX GENETIC

AAV5hFIX gene therapy

Also known as: AAV5 containing a codon-optimized human factor IX gene

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male
• Age ≥ 18 years
• Patients with congenital hemophilia B classified as one of the following:
• Known severe FIX deficiency with plasma FIX activity level \< 1% and a severe bleeding phenotype defined by one of the following:
• Currently on prophylactic FIX replacement therapy for a history of bleeding
• Currently on on-demand therapy with a current or past history of frequent bleeding defined as four or more bleeding episodes in the last 12 months or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints
• Known moderately severe FIX deficiency with plasma FIX activity level between ≥ 1% and ≤ 2% and a severe bleeding phenotype defined by one of the following:
• Currently on prophylactic FIX replacement therapy for a history of bleeding
• Currently on on-demand therapy with a current or past history of frequent bleeding defined as four or more bleeding episodes in the last 12 months or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints
• More than 150 previous exposure days of treatment with FIX protein.
• Acceptance to use a condom during sexual intercourse in the period from Investigational Medicinal Product (IMP) administration until AAV5 has been cleared from semen, as evidenced by the central laboratory from negative analysis results for at least 3 consecutively collected semen samples (this criterion is applicable also for subjects who are surgically sterilized)
• Following receipt of verbal and written information about the trial, the subject has provided signed informed consent before any trial related activity is carried out.

You may not qualify if:

• History of FIX inhibitors measured to be ≥ 0.6 Bethesda Units (BU)/mL
• FIX inhibitors ≥ 0.6 BU/mL at Visit 1 (measured by the local laboratory)
• Neutralizing antibodies against AAV5 at Visit 1 (measured by the central laboratory)
• Visit 1 laboratory values (measured by the central laboratory):
• alanine aminotransferase \> 2 times upper normal limit
• aspartate aminotransferase \> 2 times upper normal limit
• total bilirubin \> 2 times upper normal limit
• alkaline phosphatase \> 2 times upper normal limit
• creatinine \> 1.5 times upper normal limit
• Positive HIV serological test at Visit 1, not controlled with anti-viral therapy as shown by cluster of differentiation 4+ counts ≤ 200 per μL or by a viral load of \>200 copies per mL (measured by the central laboratory)
• Active infection with Hepatitis B or C virus as reflected by Hepatitis B Surface Antigen (HBsAg), Hepatitis B extracellular Antigen (HBeAg), Hepatitis B Virus DeoxyriboNucleic Acid (HBV DNA) or Hepatitis C Virus RiboNucleic Acid (HCV RNA) positivity, respectively, at Visit 1 (measured by the central laboratory).
• History of Hepatitis B or C exposure, currently controlled by antiviral therapy
• Any coagulation disorder other than hemophilia B
• Thrombocytopenia, defined as a platelet count below 50 × 10E9 / L, at Visit 1 (measured by the central laboratory)
• Body mass index \< 16 or ≥ 35 kg/m2

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (7)

uniQure Investigative Site

Copenhagen, Denmark

Location

uniQure Investigative Site

Berlin, Germany

Location

uniQure Investigative Site

Frankfurt, Germany

Location

uniQure Investigative Site

Amsterdam, Netherlands

Location

uniQure Investigative Site

Groningen, Netherlands

Location

uniQure Investigative Site

Rotterdam, Netherlands

Location

uniQure Investigative Site

Utrecht, Netherlands

Location

Related Publications (1)

• Miesbach W, Meijer K, Coppens M, Kampmann P, Klamroth R, Schutgens R, Tangelder M, Castaman G, Schwable J, Bonig H, Seifried E, Cattaneo F, Meyer C, Leebeek FWG. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood. 2018 Mar 1;131(9):1022-1031. doi: 10.1182/blood-2017-09-804419. Epub 2017 Dec 15.

  PMID: 29246900 DERIVED

MeSH Terms

Conditions

Hemophilia B

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: Study Director
• Organization: CSL Behring

clinicaltrials@cslbehring.com

610-878-4000

Study Officials

• uniQure Clinical Trials

  UniQure Biopharma B.V.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: March 24, 2015
• Study Start: June 10, 2015
• Primary Completion: April 15, 2021
• Study Completion: April 15, 2021
• Last Updated: June 27, 2022
• Results First Posted: June 27, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); DE (2); NL (4)