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NCT03489291

Dose Confirmation Trial of AAV5-hFIXco-Padua

Completed Phase 2 Results posted Last updated 28 June 2024
What this trial tests

Phase 2 trial testing AAV5-hFIXco-Padua (AMT-061) in Hemophilia B in 3 participants. Completed in 21 September 2023.

Timeline
24 July 2018
Primary endpoint
30 October 2018
21 September 2023

Quick facts

Lead sponsorCSL Behring
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment3
Start date24 July 2018
Primary completion30 October 2018
Estimated completion21 September 2023
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

CSL Behring — full company profile →

Who can join

18 and older, male only, with Hemophilia B. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Factor IX Activity Levels Primary · 6 weeks post-dose

To confirm that a single dose of 2x10\^13 gc/kg AMT-061 (CSL222) resulted in factor IX activity levels of ≥5% at 6 weeks after dosing measured by the one-stage (activated partial thromboplastin \[aPTT\]-based) assay.

GroupValue95% CI
AMT-061 (CSL222)30.6± 6.97
Annualized Exogenous Factor IX Usage Secondary · 52 weeks post-dose

Annualized use was calculated as the normalized amount of therapy administered per baseline weight, extrapolated where necessary from any time period less or greater than 1 year. Therapy administered included the total dosage of FIX given as prophylaxis and on-demand. Use for invasive procedures was not included.

GroupValue95% CI
AMT-061 (CSL222)7.1± 6.4
Annualized Bleeding Rate (ABR) Secondary · 5 years post-dose

ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.

All bleeds (Spontaneous + Traumatic + Joint)
GroupValue95% CI
AMT-061 (CSL222)0.14
Spontaneous bleeds
GroupValue95% CI
AMT-061 (CSL222)0.07
Traumatic bleeds
GroupValue95% CI
AMT-061 (CSL222)0.07
Joint bleeds
GroupValue95% CI
AMT-061 (CSL222)0.00
Factor IX Activity Levels Secondary · 52 weeks post-dose

Measured by the one-stage (aPTT-based) assay.

GroupValue95% CI
AMT-061 (CSL222)40.8± 9.45
Number of Participants Remaining Free of Continuous Prophylaxis Secondary · 1 year post-dose

Participants with no usage of continuous factor IX prophylaxis after AMT-061 (CSL222) treatment were considered free from continuous factor IX prophylaxis use.

GroupValue95% CI
AMT-061 (CSL222)3
Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis Secondary · Up to 5 years post-dose

The post-continuous-prophylaxis period began on the day after the end of continuous (routine) prophylaxis.Therapy administered included the total dosage of FIX given as prophylaxis and on-demand. Use for invasive procedures was not included.

GroupValue95% CI
AMT-061 (CSL222)342.1± 592.5
Number of Participants With Treatment Emergent (TE): Adverse Events (AE), Mild, Moderate, and Severe AEs, AEs Related and Unrelated to the Study Treatment, and Serious AEs Secondary · Up to 5 years post-dose
Participant with TEAEs
GroupValue95% CI
AMT-061 (CSL222)3
Participant with mild TEAEs
GroupValue95% CI
AMT-061 (CSL222)3
Participant with moderate TEAEs
GroupValue95% CI
AMT-061 (CSL222)2
Participant with severe TEAEs
GroupValue95% CI
AMT-061 (CSL222)2
Participants with TEAEs related to study treatment
GroupValue95% CI
AMT-061 (CSL222)1
Participants with TEAEs unrelated to study treatment
GroupValue95% CI
AMT-061 (CSL222)3
Participants with serious TEAEs
GroupValue95% CI
AMT-061 (CSL222)1
Number of Participants With Clinically Meaningful Findings in Hematology and Serum Chemistry Parameters Secondary · Up to 5 years post-dose

Clinically meaningful findings were defined as values which were outside the standard normal reference ranges for hematology and serum chemistry parameters.

GroupValue95% CI
AMT-061 (CSL222)0
Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Changes in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels Secondary · From baseline and up to 5 years post-dose

Post-baseline newly occurring or worsening potentially clinically significant ALT and AST levels were defined as values greater than twice the baseline value.

AST
GroupValue95% CI
AMT-061 (CSL222)1
ALT
GroupValue95% CI
AMT-061 (CSL222)1
Number of Participants Receiving Corticosteroids for AST and ALT Elevations Secondary · Up to 5 years post-dose
GroupValue95% CI
AMT-061 (CSL222)0
Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum Secondary · Baseline and at 5 years post-dose
At Baseline for AAV5
GroupValue95% CI
AMT-061 (CSL222)3
At 5 years post dose for AAV5
GroupValue95% CI
AMT-061 (CSL222)3
At Baseline for FIX
GroupValue95% CI
AMT-061 (CSL222)0
At 5 years post dose for FIX
GroupValue95% CI
AMT-061 (CSL222)0
Number of Participants With AAV5 Capsid-specific T Cell Response Secondary · Up to Week 52
GroupValue95% CI
AMT-061 (CSL222)1

Adverse events — posted to ClinicalTrials.gov

Time frame: 5 years post-dose. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AMT-061 (CSL222)
Serious: 1/3 (33%)
Deaths: 0/3

Serious adverse events (1 terms)

ReactionSystemAMT-061 (CSL222)
OsteonecrosisMusculoskeletal and connective tissue disorders
Other adverse events (50 terms — click to expand)

ReactionSystemAMT-061 (CSL222)
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Joint swellingMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Dental cariesGastrointestinal disorders
BronchitisInfections and infestations
COVID 19Infections and infestations
CoccidioidomycosisInfections and infestations
InfluenzaInfections and infestations
PneumoniaInfections and infestations
SinusitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Joint range of motion decreasedMusculoskeletal and connective tissue disorders
OsteonecrosisMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
HypoaesthesiaNervous system disorders
ParaesthesiaNervous system disorders
SciaticaNervous system disorders
Sinus headacheNervous system disorders
ConstipationGastrointestinal disorders
Tongue disorderGastrointestinal disorders
AstheniaGeneral disorders
Chest painGeneral disorders
Chronic fatigue syndromeGeneral disorders
PainGeneral disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood creatine phosphokinase increasedInvestigations
Blood potassium decreasedInvestigations
C reactive protein increasedInvestigations
Transaminases increasedInvestigations
TachycardiaCardiac disorders
VertigoEar and labyrinth disorders
AmblyopiaEye disorders
Cataract nuclearEye disorders
PingueculaEye disorders
PseudophakiaEye disorders
Refraction disorderEye disorders
HypersensitivityImmune system disorders
Procedural painInjury, poisoning and procedural complications

Most-reported serious reactions: Osteonecrosis.

Data from ClinicalTrials.gov NCT03489291 adverse events section.

Sponsor's own description

This is an open-label, single-dose, single-arm, multi-center trial, with a screening, a treatment + post-treatment follow-up phase, and a long-term follow-up phase. The IMP AMT-061 is a recombinant adeno-associated viral vector of serotype 5 (AAV5) containing the Padua variant of a codon-optimized human FIX complementary deoxyribonucleic acid (cDNA) under the control of a liver-specific promoter. The IMP is identified as AAV5-hFIXco-Padua (AMT- 061). The pharmaceutical form of AMT-061 is a solution for intravenous infusion. The administered dose of AMT-061 will be 2 x 10\^13 gc/kg.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer.
    Costa Verdera H, Kuranda K, Mingozzi F. · · 2020 · cited 493× · PMID 31972133 · DOI 10.1016/j.ymthe.2019.12.010
  2. Update on clinical gene therapy for hemophilia.
    Perrin GQ, Herzog RW, Markusic DM. · · 2019 · cited 128× · PMID 30559260 · DOI 10.1182/blood-2018-07-820720
  3. Anti-AAV Antibodies in AAV Gene Therapy: Current Challenges and Possible Solutions.
    Weber T. · · 2021 · cited 126× · PMID 33815421 · DOI 10.3389/fimmu.2021.658399
  4. Adeno-Associated Virus Gene Therapy for Hemophilia.
    Samelson-Jones BJ, George LA. · · 2023 · cited 97× · PMID 36103998 · DOI 10.1146/annurev-med-043021-033013
  5. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B.
    Von Drygalski A, Giermasz A, Castaman G, Key NS, et al · · 2019 · cited 95× · PMID 31698454 · DOI 10.1182/bloodadvances.2019000811
  6. Testing preexisting antibodies prior to AAV gene transfer therapy: rationale, lessons and future considerations.
    Mendell JR, Connolly AM, Lehman KJ, Griffin DA, et al · · 2022 · cited 87× · PMID 35356756 · DOI 10.1016/j.omtm.2022.02.011
  7. A Molecular Revolution in the Treatment of Hemophilia.
    Butterfield JSS, Hege KM, Herzog RW, Kaczmarek R. · · 2020 · cited 76× · PMID 31843450 · DOI 10.1016/j.ymthe.2019.11.006
  8. Gene therapy for hemophilia.
    Nathwani AC. · · 2022 · cited 74× · PMID 36485127 · DOI 10.1182/hematology.2022000388

Verify or expand the search:

Other recruiting trials for Hemophilia B

Currently open trials in the same condition.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03489291.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing