Study of efficacy and safety of INC424 in regularly transfused patients with thalassemia.

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2013-002812-28-GR
• Date of registration: 10/07/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of efficacy and safety of INC424 in regularly transfused patients with thalassemia.
• Scientific title: A single arm, multicenter, phase IIa study to explore the efficacy and safety of ruxolitinib (INC424) in regularly transfused patients with thalassemia
• Date of first enrolment: 02/09/2014
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002812-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Greece, Italy, Lebanon, Thailand, Turkey

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients 18 years of age or older
2. 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.
3. Patients with spleen enlargement at Screening, defined as
a. Spleen palpable below the costal margin, AND
b. Spleen volume of = 450 cm3 as confirmed by MRI (or CT scan in applicable patients)
4. Patients need to be on iron chelation treatment (deferoxamine or deferasirox) for at least four weeks prior to Screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Splenectomy prior to or planned during the study
2. Active serious bacterial, mycobacterial, fungal, parasitic or viral infection which requires therapy (e.g., pneumonia, tuberculosis, systemic mycosis, herpes zoster)
3. Hemoglobin <65 g/L (<4.0 mmol/L) at Screening
4. Platelet count < 75 109/L, absolute neutrophils count < 1.5 109/L at Screening
5. Estimated MDRD < 30 mL/min/1.73 m2 at Screening
6. ALT (SGPT) levels >5 times ULN at Screening
7. Hepatocellular disease such as hepatitis B (presence of HBs antigen), hepatitis C (presence of HCV RNA), liver cirrhosis
8. HIV positivity


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Thalassemia
MedDRA version: 17.0 Level: LLT Classification code 10054658 Term: Thalassemia System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Jakavi
Product Name: ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: ruxolitinib
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Other descriptive name: RUXOLITINIB PHOSPHATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week -24 to baseline period against week 6 to week 30

Primary end point(s): Percent change of RBC (Red Blood Cell) transfusion requirement between week 6 and week 30 compared to the baseline period between week -24 and the day before first study drug administration

Main Objective: To assess the effect of INC424 on transfusion requirement

Secondary Objective: Key secondary:
- to assess the effect of INC424 on spleen volume

Other secondary:
- to assess the effect of INC424 on pre transfusion hemoglobin levels
- to assess the effect of INC424 ib spleen lenght
- to assess pharmacokinetics of INC424
- to assess the safety of INC424

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: for Key secondary:
- baseline, week 12 and week 30

for Other secondary:
- baseline; week 1, 2, 3, 4, 6, 12, 18, 24, 30
- baseline; week 1, 2, 3, 4, 6, 12, 18, 24, 30
- baseline, week 2 and week 12
- baseline; week 1, 2, 3, 4, 6, 12, 18, 24, 30

Secondary end point(s): Key secondary:
- change of spleen volume from baseline measured by MRI or CT at week 12 and week 30

Other secondary:
- change of pre-transfusion hemoglobin level from baseline at each post-baseline visit
- change of spleen length from baseline over time measured by palpation
- pharmacokinetic (PK) parameters of Cmin and Cmax (1h) of INC424 by actual dose administered
- number of participants with adverse events as measure of satefy and tolerability (adverse events, serious adverse events, lab results, ECGs, vital signs)

Secondary ID(s)

CINC424X2201

Source(s) of Monetary Support

Novartis Pharma Services AG