Clinical trial NCT02049450: Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia.
Official title: A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thalassemia Major
Keywords: thalassemia
thalassemia major
spleen enlargement
INC424
ruxolitinib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-01-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 \<65 g/L (\<4.0 mmol/L) at Screening
* Platelet count \<75×109/L, absolute neutrophils count \< 1.5×109/L at Screening.
* Estimated MDRD \< 30 mL/min/1.73 m2 at Screening.
* ALT (SGPT) levels \>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

Primary outcomes:
measure: Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)
timeFrame: week 6 to week 30 interval
Secondary outcomes:
measure: Percentage Change in Spleen Volume (cm3)
timeFrame: baseline, week 12, week 30
measure: Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals
timeFrame: baseline, weeks 0 - 30
measure: Percentage Change in Spleen Length (cm) Below the Left Coastal Margin
timeFrame: baseline, weeks 1,2,3,4,6,12,18,24,30
measure: Pharmacokinetics (PK) Parameter of Cmin
timeFrame: week 2, week 12
measure: Pharmacokinetics (PK) Parameter of Cmax
timeFrame: Day 1, Week 2 (Day 15), Week 12 (Day 85)
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: