A study to test a medicine (fitusiran) injected under the skin for preventing bleeding episodes in male adolescent or adult participants with severe Hemophilia

JRCT ID: jRCT2001230001

Registered date:14/05/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Hemophilia
• Date of first enrollment: 23/08/2023
• Target sample size: 75
• Countries of recruitment: United States,Japan,Republic of Korea,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Greece,Japan,India,Japan,Italy,Japan,Mexico,Japan,South Africa,Japan,Spain,Japan,Taiwan,Japan
• Study type: Interventional

Intervention(s)

Drug: Fitusiran
Pharmaceutical form: Solution for injection, Route of administration: Subcutaneous (SC)
Drug: Clotting factor concentrates (CFC) or bypassing agents (BPA)
- Coagulation factor VIII (ATC code: B02BD02)
- Coagulation factor IX (ATC code: B02BD04)
- Coagulation factor VIIa (ATC code: B02BD08)
- Factor VIII inhibitor bypassing activity (ATC code: B02BD03)
Pharmaceutical form: Solution for infusion, Route of administration: Intravenous (IV)
Drug: Antithrombin concentrate (ATIIIC)
- Antithrombin III (ATC code: B01AB02)
Pharmaceutical form: Solution for infusion, Route of administration: Intravenous (IV)

Outcome(s)

Primary Outcome

1.Annualized bleeding rate (ABR) in the fitusiran primary efficacy period
[Time Frame baseline: Day 169 to Day 505 (since the first dose of fitusiran)]
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.

Secondary Outcome

1.Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on prophylaxis standard of care (SOC) in the SOC period
[Time Frame baseline: Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period) ]
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.
2.Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on on-demand standard of care (SOC) in the SOC period
[Time Frame baseline: Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)]
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.
3.Annualized spontaneous bleeding rate in the fitusiran primary efficacy period and in the SOC period
[Time Frame baseline: Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period) ]
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.
A spontaneous bleeding episode is a bleeding event that occurs for no apparent or known reason, particularly into the joints, muscles, and soft tissues.
4.Annualized joint bleeding rate in the fitusiran primary efficacy period and in the SOC period
[Time Frame baseline: Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period) ]
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.
A joint bleeding episode is characterized by an unusual sensation in the joint ("aura") in combination with 1) increasing swelling or warmth over the skin over the joint, 2) increasing pain, or 3) progressive loss of range of motion or difficulty in using the limb as compared with baseline.
5.Change in Haem-A-QOL physical health score and total score during SOC and during fitusiran prophylaxis
[Time Frame baseline: Day 1 (D1) to Day 505, and from D1 to Day 1009, and during SOC from Day-168 to D-1]
The Haem-A-QoL will be provided to participants >=17 years of age and includes 46 items contributing to 10 QoL domains (physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership, and sexuality). Scoring for each item is based on a 5-point Likert scale (never, rarely, sometimes, often, and all the time), and higher scores represent greater impairment.
6.Annualized bleeding rate (ABR) in the fitusiran 18-month efficacy period
[Time Frame baseline: Day 1 to Day 505]
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.
7.Annualized bleeding rate (ABR) in the fitusiran 36-month treatment period
[Time Frame baseline: Day 1 to Day 1009]
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.
8.Annualized weight-adjusted consumption of CFC/BPA
[Time Frame baseline: Day -168 until Day 1009]
All CFC or BPA doses (including doses per kg body weight) administered during the study treatment will be recorded.
9.Number of participants with adverse events
[Time Frame baseline: Date of signed ICF (Day -228 to Day -169) until last visit (approximately 50 months after date of signed ICF)]
All AEs (serious or nonserious) will be collected from the signing of the informed consent form (ICF) until last AT follow up visit.

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Male

Include criteria

- Diagnosis of severe congenital hemophilia A or B (FVIII <1% or FIX level <=2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence
- For participants currently not on prophylaxis (clotting factor concentrates [CFC] or bypassing agents [BPA] on-demand): A minimum of 4 bleeding episodes requiring BPA (inhibitor participants) or CFC (non-inhibitor participants) treatment within the last 6 months prior to screening.
- Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of participants under the age of legal consent, per local and national requirements

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Known co-existing bleeding disorders other than congenital hemophilia A or B
- History of arterial or venous thromboembolism, not associated with an indwelling venous access.
- History of intolerance to subcutaneous (SC) injection(s).
- Current participation in immune tolerance induction therapy (ITI)
- Prior gene therapy
- Current or prior participation in a fitusiran trial
- Current or prior participation in a gene therapy trial
- Received an investigational drug or device within 30 days prior to the screening visit or within 5 half-lives of the investigational drug (or device) prior to the screening visit, whichever is longer
- Presence of clinically significant liver disease
- AT activity <60% at Screening
- Co-existing thrombophilic disorder
- Hepatitis C virus antibody positive, except participants who have negative Hepatitis C viral load and no evidence of cirrhosis
- Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
- Presence of acute or chronic hepatitis B infection
- Known to be human immunodeficiency virus (HIV) positive with CD4 count <200 cells/micro L.
- Reduced renal function

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05662319,2022-500221-33-00