Phase 2
N=30
Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia.
Thalassemia Major
Bottom Line
View on ClinicalTrials.gov: NCT02049450 ↗Enrolled (actual)
30
Serious AEs
20.0%
Results posted
Jun 2017
Primary outcome: Primary: Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC) — -5.934 % change of hematocrit-adjusted volume
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ruxolitinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Apr 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC) |
-5.934 | — |
| SECONDARY Percentage Change in Spleen Volume (cm3) |
-19.733; -26.829 | — |
| SECONDARY Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals |
0.43; 2.87; 2.78; -0.56; 0.06 | — |
| SECONDARY Percentage Change in Spleen Length (cm) Below the Left Coastal Margin |
-11.19; -22.11; -25.01; -26.94; -33.85; -49.29 | — |
| SECONDARY Pharmacokinetics (PK) Parameter of Cmin |
7.5800; NA; NA; 9.1300; 18.5400; 20.2300 | — |
| SECONDARY Pharmacokinetics (PK) Parameter of Cmax |
58.2000; 126.8000; 0.00; 0.00; 56.7000; 125.400 | — |
Summary
Patients with severe thalassemia (thalassemia major) present with severe anemia that required life-long transfusion therapy, spleen enlargement that led to increased transfusion requirement, and other serious complications as early death, growth retardation, bone deformations and iron overload due to blood transfusions. Splenectomy can significantly reduce transfusion requirement in thalassemia patients, but it is associated with an increased risk of serious complications such as sepsis and thrombosis. Preliminary preclinical and clinical data suggested that JAK2 inhibition, by reducing spleen size, could improve hemoglobin levels, thereby eliminating the need for splenectomy and reducing transfusion requirement and related iron overload.
Eligibility Criteria
Inclusion Criteria
- Patients with thalassemia on a regular and stable transfusion regimen (at least 2 RBC units within every 4-week interval for 24 weeks prior to Screening) and anticipated to receive the same transfusion regimen during the study.
- Patients with spleen enlargement at Screening, defined as spleen palpable below the costal margin and spleen volume of ≥ 450 cm3 as confirmed by MRI (or CT scan in applicable patients).
- Patients need to be on iron chelation treatment (deferoxamine or deferasirox) for at least four weeks prior to Screening
Exclusion Criteria
- Splenectomy prior to or planned during the study
- Active serious bacterial, mycobacterial, fungal, parasitic or viral infection which requires therapy (e.g., pneumonia, tuberculosis, systemic mycosis, herpes zoster)
- Hemoglobin 5 times ULN at Screening.
- Hepatocellular disease such as hepatitis B (presence of HBs antigen), hepatitis C (presence of HCV RNA), liver cirrhosis.
- HIV positivity
Data sourced from ClinicalTrials.gov (NCT02049450). 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.