Thalassemia MajorPhase 2NCT02049450
Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia.
A Phase 2 study testing ruxolitinib in people with Thalassemia Major, run by Novartis Pharmaceuticals at 7 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thalassemia Major
- What is being tested?
- ruxolitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 28 May 2014to 12 Apr 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
Italy2 sites
Novartis Investigative Site
Milan, MI, 20122
Novartis Investigative Site
Palermo, PA, 90146
Turkey (Türkiye)2 sites
Novartis Investigative Site
Istanbul, 34093
Novartis Investigative Site
Izmir, 35040
About this study
Official title: A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia
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
- Being tested
- ruxolitinib
- Keywords
- thalassemia, thalassemia major, spleen enlargement, INC424, ruxolitinib
- Medical subject headings
- beta-Thalassemia, Thalassemia, Splenomegaly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ruxolitinibDrug
Also called INC424
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.
| Study group | Role | What they receive |
|---|---|---|
| INC424 (ruxolitinib) - Study Treatment | Experimental | Regularly transfused adult patients with thalassemia and spleen enlargement. Receives: Drug: ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: week 6 to week 30 interval
Secondary outcomes (5)
Percentage Change in Spleen Volume (cm3)
Change of spleen volume from baseline at week 12 and week 30 as measured by magnetic imaging resonance (MRI) or computed tomography (CT).
Measured: baseline, week 12, week 30
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals
Change from baseline in pre-transfusion hemoglobin levels
Measured: baseline, weeks 0 - 30
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin
Change of spleen length from baseline over time measured by palpitation by time
Measured: baseline, weeks 1,2,3,4,6,12,18,24,30
Pharmacokinetics (PK) Parameter of Cmin
C min of INC424 by actual dose administered from 10mg bid to 20mg bid. Plasma PK samples were collected at Day 15 (Week 2), and Day 85 (Week 12). Cmin was collected immediately prior to dosing. n= number of patients with valid PK samples as per definition of the PK analysis set.
Measured: week 2, week 12
Pharmacokinetics (PK) Parameter of Cmax
Cmax (1h) of INC424 by actual dose administered from 10mg bid to 20mg bid. Plasma PK samples were collected at Day 1, Week 2, and Week 12. Cmax was collected within a +/- 1 hour post dose.
n= number of patients with valid PK samples as per definition of the PK analysis set.
Measured: Day 1, Week 2 (Day 15), Week 12 (Day 85)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2014 (estimated)
- Study start28 May 2014
- Primary completion12 Apr 2016
- Study completion12 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Thalassemia MajorStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02049450
- Sponsor's protocol ID
- CINC424X2201
- Other IDs
- 2013-002812-28
- Status last verified
- Jun 2017
- First submitted
- 28 Jan 2014
- Last updated
- 17 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia
- ClinicalTrials.gov ID
- NCT02049450
- Acronym / sponsor ID
- CINC424X2201
- Conditions
- Thalassemia Major
- Keywords
- thalassemia, thalassemia major, spleen enlargement, INC424, ruxolitinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 28 May 2014 (actual)
- Primary completion
- 12 Apr 2016 (actual)
- Study completion
- 12 Apr 2016 (actual)
- First posted
- 30 Jan 2014 (estimated)
- Results
- Posted 15 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| INC424 (ruxolitinib) - Study Treatment | Experimental | Drug: ruxolitinibRegularly transfused adult patients with thalassemia and spleen enlargement. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ruxolitinibAlso: INC424Ruxolitinib was taken at a starting dose of 10 mg twice daily with dose adjustments within the range of 5 to 25 mg twice daily. | Drug | INC424 (ruxolitinib) - Study Treatment |
Primary outcome
Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)
Time frame: week 6 to week 30 interval
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).
5 secondary outcomes
Percentage Change in Spleen Volume (cm3)
Time frame: baseline, week 12, week 30
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals
Time frame: baseline, weeks 0 - 30
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin
Time frame: baseline, weeks 1,2,3,4,6,12,18,24,30
Pharmacokinetics (PK) Parameter of Cmin
Time frame: week 2, week 12
Pharmacokinetics (PK) Parameter of Cmax
Time frame: Day 1, Week 2 (Day 15), Week 12 (Day 85)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ruxolitinib in people with Thalassemia Major, run by Novartis Pharmaceuticals at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy, Turkey (Türkiye), Greece, Lebanon, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC) (time frame: week 6 to week 30 interval). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2017.