Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia.

NCT02049450 | Completed Phase 2 Results

• 2 other identifiers: CINC424X22012013-002812-28
• Study Type: interventional
• Target: 30
• Locations: 5 countries
• Sites: 7

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.

Conditions

Thalassemia Major

Keywords

thalassemia; thalassemia major; spleen enlargement; INC424; ruxolitinib

Outcome Measures

Primary Outcomes (1)

• Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)

  Change of RBC transfusion requirement measured as percent change of the hematocrit-adjusted volume of transfused RBC and observed during within on-treatment interval (any time-points of RBC transfusion between week 6 and week 30 driven by the individual patient's need) compared to baseline (defined by pre-treatment interval between Week - 24 to start of treatment).

  week 6 to week 30 interval

Secondary Outcomes (5)

• Percentage Change in Spleen Volume (cm3)

  baseline, week 12, week 30

• Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals

  baseline, weeks 0 - 30

• Percentage Change in Spleen Length (cm) Below the Left Coastal Margin

  baseline, weeks 1,2,3,4,6,12,18,24,30

• Pharmacokinetics (PK) Parameter of Cmin

  week 2, week 12

• Pharmacokinetics (PK) Parameter of Cmax

  Day 1, Week 2 (Day 15), Week 12 (Day 85)

Study Arms (1)

INC424 (ruxolitinib) - Study Treatment

EXPERIMENTAL

Regularly transfused adult patients with thalassemia and spleen enlargement.

Drug: ruxolitinib

Interventions

ruxolitinib DRUG

Ruxolitinib was taken at a starting dose of 10 mg twice daily with dose adjustments within the range of 5 to 25 mg twice daily.

Also known as: INC424

INC424 (ruxolitinib) - Study Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

Athens, GR, GR-115 27, Greece

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Palermo, PA, 90146, Italy

Location

Novartis Investigative Site

Beirut, 1107 2020, Lebanon

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia; Splenomegaly

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2014
• First Posted: January 30, 2014
• Study Start: May 28, 2014
• Primary Completion: April 12, 2016
• Study Completion: April 12, 2016
• Last Updated: July 17, 2017
• Results First Posted: June 15, 2017

Record last verified: 2017-06

Locations

TU (2); LE (1); TH (1); GR (1); IT (2)