Phase 2
Completed N=34
An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B
Source: ClinicalTrials.gov NCT02554773 ↗Enrolled (actual)
34
Serious AEs
26.9%
Results posted
Jun 2024
Primary outcomePrimary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) — 33; 14; 13; 1 Participants
Summary
Primary Objective:
To evaluate the long-term safety and tolerability of fitusiran in male patients with moderate or severe hemophilia A or B
Secondary Objectives:
* To investigate the long-term efficacy of fitusiran
* To characterize the safety and efficacy of concomitantly administered Factor VIII (FVIII), Factor IX (FIX) or bypassing agents (BPA) and fitusiran for treatment of bleeding episodes
* To assess changes in health-related quality of life (QOL) over time
* To characterize antithrombin (AT) reduction and thrombin generation (TG) increase
* To characterize the pharmacokinetics (PK) of fitusiran
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) |
33; 14; 13; 1; 11; 1 | — |
| PRIMARY Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology |
5; 2; 3; 1; 10; 3 | — |
| PRIMARY Number of Participants With Potentially Clinically Significant Abnormality: Clinical Chemistry |
13; 2; 10; 2; 20; 7 | — |
| PRIMARY Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis |
0; 0 | — |
| PRIMARY Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs |
1; 0; 1; 0; 8; 3 | — |
| PRIMARY Number of Participants With Potentially Clinically Significant Abnormality: Electrocardiogram (ECG) |
1; 0; 8; 5; 3; 1 | — |
| PRIMARY Number of Participants With Potentially Clinically Significant Abnormality: Physical Examination |
17; 2 | — |
| SECONDARY Annualized Bleeding Rate (ABR) During the Efficacy Period |
3.035; 3.929 | — |
| SECONDARY Annualized Spontaneous Bleeding Rate During the Efficacy Period |
2.60; 3.96 | — |
| SECONDARY Annualized Joint Bleeding Rate During the Efficacy Period |
3.51; 4.78 | — |
| SECONDARY Time Intervals Between Bleeding Events |
368.50; 249.00 | — |
| SECONDARY Annualized Weight-Adjusted Consumption of Coagulation Factor VIII (FVIII) and Coagulation Factor IX (FIX) |
63.66; 52.13; 110.26; 108.63 | — |
| SECONDARY Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Recombinant Factor VIIa (rFVIIa) |
1316.19; 1431.84 | — |
| SECONDARY Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Activated Prothrombin Complex Concentrate (aPCC) |
381.81 | — |
| SECONDARY Change From Baseline in EuroQoL 5-Dimension 5-level Questionnaire (EQ-5D-5L) Index and Visual Analog Scale (VAS) Scores at Month 24 |
0.01; 0.09; 4.73; 16.67 | — |
| SECONDARY Change From Baseline in Hemophilia Quality of Life Questionnaire (Haem-A-QoL) Total Score and Physical Health Scores at Month 24 |
-0.20; 0.02; -0.14; -0.53 | — |
| SECONDARY Antithrombin Activity Level at the End of Treatment Regimen |
16.28; 24.76 | — |
| SECONDARY Thrombin Generation at the End of Treatment Regimen |
71.39; 32.31 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Fitusiran |
86.8; 168; 75.2; 149; 62.5; 155 | — |
| SECONDARY Time to Reach the Maximum Concentration (Tmax) of Fitusiran |
3.97; 4.00; 4.02; 6.00; 4.00; 7.83 | — |
| SECONDARY Area Under the Concentration Versus Time Curve From Time 0 to the Real Time (AUClast) of Fitusiran |
1110; 2130; 961; 2020; 935; 2070 | — |
| SECONDARY Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of Fitusiran |
1470; 2230; 356; 2860 | — |
| SECONDARY Terminal Half-Life (t1/2z) of Fitusiran |
5.19; 5.90; 3.91; 4.94 | — |
| SECONDARY Apparent Total Body Clearance (CL/F) of Fitusiran |
37.6; 38.8; 143; 28.3 | — |
| SECONDARY Apparent Volume of Distribution at the Steady State After Single Extravascular Dose (Vss/F) of Fitusiran |
283; 390; 834; 204 | — |
| SECONDARY Recovery of Fraction of the Dose Excreted in Urine (fe) in 0-24 Hours After Fitusiran Administration |
10.7; 12.6 | — |
Eligibility Criteria
Inclusion Criteria
- Completed and tolerated study drug dosing in study TDR14767 (ALN-AT3SC-001)
- Male aged ≥18 years
- Moderate or severe, clinically stable hemophilia A or B as evidenced by a laboratory FVIII or FIX level ≤5% at screening. Patients with a FVIII or FIX level >5% at screening will be eligible on provision of a historic laboratory report indicating a trough level ≤5%
- Willing and able to comply with the study requirements and provide written informed consent
Exclusion Criteria
- Clinically significant liver disease
- Patients known to be human immunodeficiency virus seropositive and have a CD4 count <200 cells/μL
- History of venous thromboembolism
- Current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity
- Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory, or other diseases that, in the judgment of the Investigator, precludes study participation
Data sourced from ClinicalTrials.gov (NCT02554773). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.