Study of Ruxolitinib (INCB018424) Sustained Release Formulation in Myelofibrosis Patients

Myelofibrosis Clinical Trial

Official title:

An Open-label Assessment of Once-daily Dosing of a Sustained Release (SR) Formulation of INCB018424 in Patients With Primary Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, and Post-polycythemia Vera Myelofibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01340651
• Other study ID #: 18424-260
• Status: Completed
• Phase: Phase 2
• First received: April 21, 2011
• Last updated: February 5, 2014
• Start date: March 2011
• Est. completion date: July 2012

Study information

• Verified date: December 2013
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and tolerability of ruxolitinib (INCB018424) sustained release (SR) formulation in participants with primary myelofibrosis (PMF), post-polycythemia vera MF (PPV-MF), and post-essential thrombocythemia MF (PET-MF).

Description:

The study will enroll approximately 40 participants with PMF, PPV-MF or PET-MF. Participants will take ruxolitinib SR once daily for 16 consecutive weeks and then transition to a comparable twice daily dose regimen of ruxolitinib using the immediate release (IR) tablets which have been under investigation in controlled Phase 1, 2, and 3 clinical trials.

Participants receiving benefit from treatment with ruxolitinib may continue further participation with IR tablets up to the time when the last participant completed Week 36 or the commercial availability of ruxolitinib IR, whichever was earlier. Follow-up will occur at least 30 days following the last dose of ruxolitinib.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants 18 years of age or older.

• Participants must be diagnosed with primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (PPV-MF), or post-polycythemia vera myelofibrosis (PET-MF).

• Participants with myelofibrosis requiring therapy must be classified as high risk (3 or more prognostic factors), intermediate risk level 2 (2 prognostic factors), or intermediate risk level 1 (1 prognostic factor)defined by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT).

• Participants must have a palpable spleen measuring 5 cm or greater below the costal margin.

Exclusion Criteria:

• Participants with a life expectancy of less than 6 months.

• Participants of childbearing potential who are unwilling to take appropriate precautions to avoid pregnancy or fathering a child.

• Participants with inadequate bone marrow reserve.

• Participants with history of platelet counts < 50,000/µL, platelet transfusion(s), or an absolute neutrophil count < 500/µL in the month prior to Screening.

• Participants with inadequate liver or renal function at Screening and Baseline visits.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• Ruxolitinib
Ruxolitinib was supplied as SR and IR formulated tablets.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With at Least 1 Adverse Event From Baseline Through Week 16		Baseline to Week 16	Yes
Primary	Overall Response (OR) at Week 16	The investigator graded OR according to the International Working Group for Myelofibrosis Research and Therapy criteria for treatment response. As bone marrow biopsies were not taken after baseline, the best achievable response was clinical improvement which required 1 of the following in the absence of progressive disease (PD): (1) A = 2 g/dL increase in hemoglobin level or (2) either a palpable = 50% reduction of splenomegaly of a spleen = 10 cm at baseline or a spleen palpable at > 5 cm at baseline becoming not palpable. PD required 1 of the following: (1) Progressive splenomegaly defined by the appearance of previously absent splenomegaly that was palpable at > 5 cm below the left costal margin or a = 100% increase in palpable distance for baseline splenomegaly of 5-10 cm or a = 50% increase in palpable distance for baseline splenomegaly of > 10 cm or (2) an increase in peripheral blood blast percentage to = 20% that lasted for = 8 weeks. Stable disease: None of the above.	Baseline to Week 16	No
Secondary	Change From Baseline in Spleen Volume at Week 16	Spleen volume was measured by magnetic resonance imaging (or by computed tomography [CT] in applicable participants). Scans were read by a central reader. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares.	Baseline to Week 16	No
Secondary	Change From Baseline in Spleen Length at Week 16	Spleen length was measured in centimeters by palpation.	Baseline to Week 16	No
Secondary	Percentage of Participants With = 35% Reduction in Spleen Volume at Week 16 From Baseline	Spleen volume was measured by magnetic resonance imaging (or by computed tomography [CT] in applicable participants). Scans were read by a central reader. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares.	Baseline to Week 16	No
Secondary	Change From Baseline in the Total Symptom Score at Week 16	Symptoms of myelofibrosis were assessed using the modified Myelofibrosis Symptom Assessment Form v2.0 diary that was to be completed by participants each night. The 7 symptoms (night sweats, itchiness, abdominal pain, pain under the ribs on left side, feeling of fullness [early satiety], bone/muscle pain, inactivity) were each rated on a scale from 0 (absent) to 10 (worst imaginable). The total symptom score was the sum of 6 of the 7 symptoms (inactivity was not included) and ranged from 0 to 60. A lower score indicated fewer symptoms. A negative change score indicated improvement.	Baseline to Week 16	No
Secondary	Percentage of Participants With a = 50% Reduction From Baseline in the Total Symptom Score at Week 16	Symptoms of myelofibrosis were assessed using the modified Myelofibrosis Symptom Assessment Form v2.0 diary that was to be completed by participants each night. The 7 symptoms (night sweats, itchiness, abdominal pain, pain under the ribs on left side, feeling of fullness [early satiety], bone/muscle pain, inactivity) were each rated on a scale from 0 (absent) to 10 (worst imaginable). The total symptom score was the sum of 6 of the 7 symptoms (inactivity was not included) and ranged from 0 to 60. A lower score indicated fewer symptoms.	Baseline to Week 16	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib 25 mg SR on Day 1	Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. Standard non-compartmental pharmacokinetic methods were used to analyze the ruxolitinib plasma concentration data using WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA). Cmax was taken directly from the observed plasma concentration data.	Day 1	No
Secondary	Time to Reach the Maximum Plasma Concentration (Tmax) of Ruxolitinib 25 mg SR on Day 1	Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. Standard noncompartmental pharmacokinetic methods were used to analyze the ruxolitinib plasma concentration data using WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA). Tmax was taken directly from the observed plasma concentration data.	Day 1	No
Secondary	Area Under the Plasma Concentration-time Curve (AUC) of Ruxolitinib 25 mg SR on Day 1	Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. The area under the plasma concentration-time curve (AUC) was derived from the plasma concentrations using a non-compartmental method and computed using the linear trapezoidal rule for increasing concentrations and the log-trapezoidal rule for decreasing concentrations with the software WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA).	Day 1	No