• ClinicalTrials.gov Identifier: NCT02618915¹  (101HEMB01 study) and NCT02971969² (101HEMB02 long-term study)
• A Phase I/II Open-Label, Safety and Dose Finding Study 

NCT02618915¹  (101HEMB01 study)

• Terminated (Sponsor decision, not due to any safety concerns related to DTX101)1
• Last Update Posted: 2018-11-14

 NCT02971969² (101HEMB02 long-term study)

• Completed
• Last Update posted: 2022-01-06

• Male ≥ 18 years of age.
• Moderate/severe or severe hemophilia B (baseline FIX activity ≤ 2% of normal or documented history of FIX activity ≤2%)
• At least 100 days exposure history to FIX

• Anti-AAVrh10 neutralizing antibody titer > 1:5
• Participation (current or previous) in another gene therapy study.

AAVrh10¹/ not reported

Codon-optimized FIX-WT³

The expression cassette³ includes

• Liver-specific enhancer element
• Liver-specific promoter element

Systemic⁴

• Co. 1: 1.6e12 (3)
• Co. 2: 5.0e12 (3)

Follow-up periods for six 18-year-old male subjects with moderate to severe hemophilia B in the 101HEMB01 and 101HEMB02 studies, as reported in Reference #6, are summarized below:

• 101HEMB01 (Safety and efficacy of treatment)
  • Study End
    • Co 1 (1.6 x 10¹² GC/kg) : Week 52
    • Co 2 (5 x 10¹² GC/kg): Week 44
• 101HEMB02 (long-term safety, tolerability, and efficacy study)
  • Follow-up Period
    • Study visits at Weeks 16, 52, 104, 156
  • End if Study Visit
    • Co 1 (1.6 x 10¹² GC/kg): Week 208
    • Co 2 (5 x 10¹² GC/kg): Week 216

OS¹

Early and long-term follow-up data on FIX activity following gene therapy, as reported in reference #6, are summarized in the table and notes below:

Notes:

• All participants resumed standard FIX therapy early in follow-up (from week 1 to week 18) due to low FIX levels
• FIX activity not assessed for:
  • 1 participant in Cohort 1 at Week 156.
  • 2 participants in Cohort 1 at Week 208 (due to COVID-19 restrictions)
     

More detailed data on FIX activity levels following gene therapy were extracted from ClinicalTrials.gov¹ and are summarized in the table below:

Data on mean time to peak FIX response, as published in reference #3, are summarized below:

• An asymptomatic rise in alanine aminotransferase (ALT) level was observed
  • at approximately the time of peak FIX level and was followed
  • by a gradual reduction in FIX level to near baseline in all but one subject

Data on the annualized bleeding rate, as published in reference #3, are summarized below:

The use of recombinant FIX during the 101HEMB01 and 101HEMB02 studies after DTX101 administration was otlined in Reference #6 as follows:

• Following DTX101 administration, both Cohort 1 (lower dose) and Cohort 2 (higher dose) showed initial increases in FIX activity levels
• Over time, FIX activity declined and became variable during the remainder of the 101HEMB01 study and throughout the 101HEMB02 follow-up
• All participants eventually required recombinant FIX replacement therapy to maintain adequate FIX activity for disease management

Data on the annualized use of FIX replacement therapy during the first year after DTX101 administration, as published in Reference #1, are summarized below:

• See reference #1 for data on average weekly use of FIX replacement therapy

No infusion related reactions reported

The most recent data on treatment-emergent adverse events (TEAEs) from the 101HEMB01 and 101HEMB02 studies—reported in Table 2 (left) for overall TEAEs and Table 3 (right) for related TEAEs of Reference #6—are summarized below.

               Data arepresented as n (%)

ALT elevations reported as adverse events (AEs) during the early follow-up period (≥32 weeks) of the 101HEMB01 study were derived from Reference #3 and are summarized as follows:

• Four subjects experienced Grade 1 or 2 ALT elevations (≤3.0 or ≤5.0 times the upper limit of normal).
• Subject 6 had a severe Grade 4 ALT elevation with a peak ALT of 914 U/L, which normalized following initiation of steroid therapy.
• Subjects 4 and 5 experienced mild ALT rises after completing the steroid protocol, associated with additional loss of FIX activity.
• In most subjects, ALT elevation coincided with peak FIX levels but was followed by a gradual decline in FIX activity toward baseline despite steroid treatment.
• No subjects developed FIX inhibitors during the study.

Summaries of TEAEs (left table)—defined as events not present before exposure to the study product or as pre-existing events that worsened in severity or increased in frequency following exposure—and reported SAEs (right table) were
extracted from ClinicalTrials.gov (Reference #1) and are presented below:

Not reported

Recently published data on ALT elevations during the 101HEMB01 and 101HEMB02 studies after DTX101 administration were extracted from Reference #6 and are summarized below in both table and bullet point format.

• In the 101HEMB01 study, ALT and AST levels rose in some participants in both cohorts after DTX101 administration
• Greater transaminase elevations were seen in Co. 2 (2e13 gc/kg), who received the higher dose of DTX101
• Steroid treatment was initiated in participants with transaminase-related treatment-emergent adverse events (TEAEs)
• All participants remained asymptomatic, and ALT elevations resolved with steroid intervention
• In Co. 2 (2e13 gc/kg), one participant had a sharp ALT rise to 914 U/L on Day 30, triggering a predefined stopping criterion
  • Treated with oral prednisone (60–100 mg/day)
  • ALT normalized by Day 279
• During the 101HEMB02 study, no ALT elevations were observed, and transaminase levels stayed within normal limits throughout

Earlier published data on the peak levels and timing of ALT elevations were extracted from Reference #3 and are summarized as follows:

• In 4/6 pts. peak ALT values ≤3.0 or ≤5.0 x ULN were considered either as Grade 1 or 2 AEs
• In 1/6 pts. peak ALT value of 914 U/L was considered as Grade 4 AE
• Rise in ALT levels were observed at approx. the time of peak FIX level between 8 -14 weeks

Not reported

Data on capsid-directed T-cell immune activation were extracted from Reference #5 and are summarized as follows:

• 4/6 (described as limited/6-8 weeks)
• 1/6 in Co. 2 with strong CD4+ T, IL-2+, IFNγ+ response to FIX that did not persist            

Normalised ALT levels but did not prevent FIX loss in most patients³

• Yes, 5/6 (gradual reduction to baseline levels in all but 1 participant)³

Not reported

1. Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/​Severe to Severe Hemophilia B. Available at: Study Details | Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B | ClinicalTrials.gov
2. Long-Term Safety, Tolerability, and Efficacy of DTX101 (AAVrh10FIX) in Adults With Moderate/​Severe to Severe Hemophilia B.  Available at: No Study Results Posted | Long-Term Safety, Tolerability, and Efficacy of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B | ClinicalTrials.gov
3. Pipe, S., et al., 101HEMB01 Is a Phase 1/2 Open-Label, Single Ascending Dose-Finding Trial of DTX101 (AAVrh10FIX) in Patients with Moderate/Severe Hemophilia B That Demonstrated Meaningful but Transient Expression of Human Factor IX (hFIX). Blood, 2017. 130(Suppl. 1): p. 3331. 101HEMB01 Is a Phase 1/2 Open-Label, Single Ascending Dose-Finding Trial of DTX101 (AAVrh10FIX) in Patients with  Moderate/Severe Hemophilia B That Demonstrated Meaningful but Transient Expression of Human Factor IX (hFIX) - ScienceDirect
4. Nathwani, A.C., Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program, 2019. 2019(1): p. 1-8. Gene therapy for hemophilia | Hematology, ASH Education Program | American Society of Hematology (ashpublications.org)
5. Calcedo, R., et al., Immune Responses in 101HEMB01, a Phase 1/2 Open-Label, Single Ascending Dose-Finding Trial of DTX101 (AAVrh10FIX) in Patients with Severe Hemophilia B. Blood 2017. 130(Suppl. 1): p. 3333. Immune Responses in 101HEMB01, a Phase 1/2 Open-Label, Single Ascending Dose-Finding Trial of DTX101 (AAVrh10FIX) in Patients with Severe Hemophilia B | Blood | American Society of Hematology (ashpublications.org)
6. Pipe S, Poma A, Rajasekhar A, Everington T, Sankoh S, Allen J, Cataldo J, Crombez E. Gene therapy for hemophilia B: results from the phase 1/2 101HEMB01/02 studies. Blood Adv. 2025 Jun 24;9(12):2980-2987. doi: 10.1182/bloodadvances.2024015184. PMID: 40197980; PMCID: PMC12197983. Gene therapy for hemophilia B: results from the phase 1/2 101HEMB01/02 studies - PubMed

AAV, Adeno-associated virus; ABR, Annualized bleeding rate; AEs, adverse events; AIR, Annualized FVIII/FIX infusion rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CH, Chromogenic Assay; Co., cohort; DOACs, Direct oral anticoagulants; D, days; EDs, exposure days; FIX, factor IX; FIX-Padua, gain of function FIX variant; FVIII, factor VIII; gc, genome copies; HEK cells, human embryonic kidney cells; IQR, interquartile range; IRR, Infusion-related reaction; NAbs, neutralizing antibodies; OS, One-stage clotting assay; Pop., population; pt., patient/participant; pts., patients/participants; P1, Participant 1; PI, phase I; PBGD, porphobilinogen deaminase; PBMC, peripheral blood mononuclear cells; SAEs, serious adverse events; SFU, spot-forming units; TAC, tacrolimus; ULN, upper limit of normal; VCN, vector copy number; vg, vector genomes; W, weeks; WT, wild type; Y, year