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Trial record 8 of 22 for:    "Hemosiderosis" | "Chelating Agents"

Safety Study of Crushed Deferasirox Film Coated Tablets in Pediatric Patients With Transfusional Hemosiderosis (MIMAS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03372083
Recruitment Status : Active, not recruiting
First Posted : December 13, 2017
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The study employs an interventional, prospective, single arm, open label, global, multicenter,non-randomized trial design to monitor and assess the safety profile of the crushed deferasirox FCT in pediatric patients between age ≥2 to <6 with transfusional hemosiderosis over 24 weeks. This study will aim to enroll at least 40 patients.

Condition or disease Intervention/treatment Phase
Iron Over Load Drug: Deferasirox Phase 4

Detailed Description:
  • The study will include a screening period (from Day 0-14) with two visits at least 7 days apart to assess eligibility of patients that are chelation naïve or on a prior iron chelator treatment other than DFX. For Patients on DFX treatment prior to study entry only one screening visit (screening visit 1) will occur to determine eligibility. Any current chelation therapy except deferasirox will be discontinued to undergo a 5-day washout period prior to commencing a 24 week treatment period with crushed deferasirox FCT.
  • All patients will have weekly visits for the first month to monitor renal function. Hepaticfunction will be assessed biweekly during the first month. Thereafter, monthly safety assessments will be performed, including the monitoring of serum ferritin values and trends in order to adapt patient treatment.

Eligibility, application of dosing standards and adjustments, as well as safety and serum ferritin assessments as specified in the protocol, will occur in accordance with the EU label throughout the study.

- Patients will continue therapy up to 24 weeks.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-arm Interventional Phase IV, Post-authorisation Study Evaluating the Safety of Pediatric Patients With Transfusional Hemosiderosis Treated With Deferasirox Crushed Film Coated Tablets
Actual Study Start Date : January 16, 2018
Estimated Primary Completion Date : November 14, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Iron
Drug Information available for: Deferasirox

Arm Intervention/treatment
Experimental: Deferasirox
Crushed deferasirox (ICL670) FCT for oral use daily. Deferasirox FCT dosing is based on subject's weight
Drug: Deferasirox
Deferosirox is provided in tablet forms of 90, 180 and 360mg. Tablets must be crushed.
Other Name: ICL670




Primary Outcome Measures :
  1. Percentage of patients with selected gastrointestinal disorders up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    To assess the safety of crushed deferasirox FCT with respect to selected gastrointestinal (GI) disorders (esophagitis, stomatitis, mouth ulceration, gastric ulcers, haemorrhage, abdominal pain, diarrhea, nausea, and vomiting)


Secondary Outcome Measures :
  1. Percentage of patients who experienced AEs suspected to be related to study drug up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    Evaluate AEs suspected to be related to the crushed deferasirox FCT

  2. Change from baseline ECGs up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    12-lead ECGs will be obtained for each subject during the study. ECG data will be read and interpreted centrally. Any clinically significant (notable) changes will be reported (which may include PR, QRS, QT, QTcF and HR intervals, if appropriate). Clinically significant abnormalities will be reported as adverse events.

  3. Change from baseline serum ferritin (SF) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    To assess the efficacy of deferasirox FCT treatment.Absolute change from baseline over time in SF values up to 24 weeks of treatment will be provided

  4. Absolute change for serum creatinine up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    To assess the overall safety of crushed FCT of deferasirox for predetermined acceptable lab values

  5. Absolute change for creatinine clearance UPCR up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    To assess the overall safety of crushed FCT of deferasirox for predetermined acceptable lab values. UPCR=urine protein to creatinine ratio

  6. Absolute change for total bilirubin up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    To assess the overall safety of crushed FCT of deferasirox for predetermined acceptable lab values

  7. Absolute change for alkaline phosphatase (ALP) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    To assess the overall safety of crushed FCT of deferasirox for predetermined acceptable lab values of ALP(alkaline phosphatase).

  8. Change in Mean Domain Scores of the Modified Satisfaction With Iron Chelation Therapy (Modified SICT) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    The mSICT questionnaire will be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire will be considered as baseline. The modified SICT consists of 20 items that represent 3 domains: Adherence, Preference and Concerns

  9. Palatability Questionnaire Score up to 24 weeks [ Time Frame: Baseline (screening Visit 1) up to approximately 24 weeks ]

    The palatable questionnaire will be completed at screening visit 1, week 4, week 12, and EOT. The responses at screening visit 1 for palatable questionnaire will be considered as baseline. The palatability questionnaire consists of 4 items. Two items measure the taste Item 1 and aftertaste (Item 2) of the medication and are scored on a 5-point response scale with the response format Very good =1 (best), Good=2,Neither good nor bad =3, Bad=4, and Very bad=5 (worst).

    The aftertaste item will be treated as an independent item (and will not be part of the scoring) and will be presented descriptively.


  10. Change in GI Symptoms to 24 weeks [ Time Frame: Baseline (screening Visit 1) up to approximately 24 weeks ]
    The GI symptom questionnaire consists of 6 items, 5 of which are scored using a 1-5 rating scale with appropriate end anchors to rate the symptom. The items are Pains in the belly, Nausea (feeling like throwing up), Vomiting, Constipation and Diarrhea. All are scored as Always=5 (worst), Most of the time=4, Sometimes=3, Rarely=2, Never=1 (best). The sixth item assesses number of bowel movements during the past week with 7 possible responses: 0 to 4, 5=5 to 10 and 6 = greater than 11

  11. Change from baseline in systolic and diastolic blood pressures(mmHg) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    The change from baseline in systolic and diastolic blood pressures(mmHg) will be summarized using descriptive statistics.

  12. Change from baseline Ocular assessments up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    Ocular assessments will be performed at screening, EOT and as needed basis and will include: Distance visual acuity test, Applanation tonometry, lens photography, wide angle fundus photography of the retina and optic nerve. Clinically significant abnormalities will be reported as adverse events.

  13. Change from baseline auditory assessments up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    Auditory assessments will be performed at screening, EOT and as needed basis: comprehensive audiometry threshold examination, speech recognition. The data will be summarized using the Safety set. Clinically significant abnormalities will be reported as adverse events.

  14. Absolute change for ALT(alanine aminotransferase) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    To assess the overall safety of crushed FCT of deferasirox for predetermined acceptable lab values for ALT(alanine aminotransferase)

  15. Absolute change for AST( Aspartate aminotransferase) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    To assess the overall safety of crushed FCT of deferasirox for predetermined acceptable lab values for AST ( Aspartate aminotransferase)

  16. Change from baseline height(cm) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    The change from baseline in height(cm) will be summarized using descriptive statistics.

  17. Change from baseline in weight(kg) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    The change from baseline in weight(kg) will be summarized using descriptive statistics.

  18. Change from baseline in temperature(°C), up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    The change from baseline in temperature(°C) will be summarized using descriptive statistics.

  19. Change from baseline in supine bolld pressure (mmHg) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    The change from baseline in supine blood pressure (mmHg) will be summarized using descriptive statistics.

  20. Change from baseline in supine pulse rate(bpm) up to 24 weeks [ Time Frame: Baseline up to approximately 24 weeks ]
    The change from baseline in supine pulse rate(bpm) will be summarized using descriptive statistics.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients ≥2 to <6 years old diagnosed with transfusional hemosiderosis
  2. Documented history of red blood cell transfusions
  3. Written informed consent/assent before any study-specific procedures. The consent will be obtained from caregiver(s) or patient's legal representative. Investigators will also obtain assent of patients according to local, regional, or national regulations.
  4. For patients on prior DFX: Serum ferritin (SF) >500 ng/mL, measured at screening visit 1 and requiring a DFX daily dose equivalent to FCT ≥ 7mg/kg/day.
  5. For patients on a prior chelator other than DFX (e.g. deferiprone or deferoxamine) or chelation naive: Serum ferritin (SF) >1000 ng/mL measured at screening visits 1 and 2.

Exclusion Criteria:

  1. Patients that receive more than one iron chelator at the same time as current iron chelation treatment. (Patients who have received combination therapy in their medical history but are currently being treated with a single ICT agent are eligible.)
  2. Patients continuing on deferoxamine or deferiprone in addition to study treatment.

    (Patients switching to or continuing on deferasirox are eligible).

  3. Unresolved adverse events if the patient was previously treated with deferiprone or deferoxamine or deferasirox.
  4. Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void sample urine measured at screening visit 1.
  5. Serum creatinine > age adjusted ULN measured at any screening visit
  6. Creatinine clearance below 90 mL/minute measured at any screening visit. Creatinine clearance using the Schwartz formula will be estimated from serum creatinine measured at each respective visit.
  7. ALT and/or AST > 2.5 x ULN measured at screening visit 1.
  8. Total bilirubin (TBIL) >1.5 x ULN measured at screening visit 1.
  9. Patients with significant impaired GI function or GI disease that may significantly alter the absorption of oral deferasirox FCT (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  10. History of and/or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive.
  11. Liver disease with severity of Child-Pugh Class B or C.
  12. History of hypersensitivity to any of the study drug or excipients.
  13. Patients participating in another clinical trial or receiving an investigational drug.
  14. Patients with a known history of HIV seropositivity.
  15. Patients unwilling or unable to comply with the protocol.
  16. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
  17. Significant medical condition interfering with the ability to partake in this study (e.g.

    uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease: cardiovascular, renal, hepatic, etc.).

  18. Female patients who reach menarche and they or their caregivers refuse pregnancy testing and/or if there is a positive pregnancy test result.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03372083


Locations
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Egypt
Novartis Investigative Site
Zagazig, Egypt, 44519
Italy
Novartis Investigative Site
Cona, FE, Italy, 44100
Novartis Investigative Site
Cagliari, ITA, Italy, 09121
Novartis Investigative Site
Napoli, Italy, 80138
Lebanon
Novartis Investigative Site
Hazmiyeh, Beirut, Lebanon, PO BOX 213
Oman
Novartis Investigative Site
Muscat, Oman, 123
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 117198
Thailand
Novartis Investigative Site
Bangkok noi, Bangkok, Thailand, 10700
Novartis Investigative Site
Muang, Chiangmai, Thailand, 50200
United Arab Emirates
Novartis Investigative Site
Dubai, United Arab Emirates, 9115
United Kingdom
Novartis Investigative Site
London, United Kingdom, NW1 2BU
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03372083     History of Changes
Other Study ID Numbers: CICL670F2429
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Iron Chelation Therapy
Deferasirox
Asunra
Jadenu
Exjade
ICL 670
Pediatric
Additional relevant MeSH terms:
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Hemosiderosis
Iron Overload
Iron Metabolism Disorders
Metabolic Diseases
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action