Iron OverloadPhase 4MIMASNCT03372083
Safety Study of Crushed Deferasirox Film Coated Tablets in Pediatric Patients With Transfusional Hemosiderosis
A Phase 4 study testing Deferasirox in people with Iron Overload, run by Novartis Pharmaceuticals at 10 sites in 7 countries.
Trial summary
This study employed a prospective, single-arm, global multi-center interventional open-label, non-randomized design to identify and assess safety profile of the crushed deferasirox FCT when administered up to 24 weeks in pediatric patients aged ≥2 to <6 years with transfusional hemosiderosis. Read more about this study
- Who is it for?
- Ages 2 to 6 years
- Conditions the study is for
- Iron Overload
- What is being tested?
- Deferasirox
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 10 sitesin 7 countries
- Study dates
- 16 Jan 2018to 5 Dec 2019
- Phase
- Phase 4
- 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 2 to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients ≥2 to <6 years old diagnosed with transfusional hemosiderosis
- Documented history of red blood cell transfusions
- 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.
- 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.
- 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.
Who cannot join
- 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.)
- Patients continuing on deferoxamine or deferiprone in addition to study treatment. (Patients switching to or continuing on deferasirox are eligible).
- Unresolved adverse events if the patient was previously treated with deferiprone or deferoxamine or deferasirox.
- 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.
- Serum creatinine > age adjusted ULN measured at any screening visit
- 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.
Show all 18Show fewer
- ALT and/or AST > 2.5 x ULN measured at screening visit 1.
- Total bilirubin (TBIL) >1.5 x ULN measured at screening visit 1.
- 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).
- 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.
- Liver disease with severity of Child-Pugh Class B or C.
- History of hypersensitivity to any of the study drug or excipients.
- Patients participating in another clinical trial or receiving an investigational drug.
- Patients with a known history of HIV seropositivity.
- Patients unwilling or unable to comply with the protocol.
- 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.
- 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.).
- Female patients who reach menarche and they or their caregivers refuse pregnancy testing and/or if there is a positive pregnancy test result.
Trial locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
Italy3 sites
Novartis Investigative Site
Cagliari, ITA, 09121
Novartis Investigative Site
Cona, FE, 44100
Novartis Investigative Site
Naples, 80138
Thailand2 sites
Novartis Investigative Site
Bangkok Noi, Bangkok, 10700
Novartis Investigative Site
Muang, Chiangmai, 50200
United Arab Emirates1 site
Novartis Investigative Site
Dubai, 9115
About this study
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
This study employed a prospective, single-arm, global multi-center interventional open-label, non-randomized design to identify and assess safety profile of the crushed deferasirox FCT when administered up to 24 weeks in pediatric patients aged ≥2 to <6 years with transfusional hemosiderosis. The study was designed to enroll a minimum of 40 patients. Forty-four patients were treated and analyzed.
Read the detailed description
The study included a screening period (from Day 0-14) with two visits at least 7 days apart to assess eligibility of patients that were 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) were to occur to determine eligibility. Any current chelation therapy except deferasirox were to be discontinued to undergo a 5-day washout period prior to commencing a 24 week treatment period with crushed deferasirox FCT.
All patients were to have weekly visits for the first month to monitor renal function. Hepatic function were to be assessed biweekly during the first month. Thereafter, monthly safety assessments were to 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.
The planned duration of treatment was 24 weeks followed by a 30-day safety follow up.
- Conditions
- Iron Overload
- Being tested
- Deferasirox
- Keywords
- Iron Chelation Therapy, Deferasirox, Asunra, Jadenu, Exjade, ICL 670, Pediatric
- Medical subject headings
- Iron Overload
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeferasiroxDrug
Also called ICL670
Deferosirox was provided in tablet forms of 90, 180 and 360mg. Tablets were crushed in the home environment and administered by sprinkling the full dose on to soft food to be consumed immediately.
| Study group | Role | What they receive |
|---|---|---|
| Deferasirox | Experimental | Crushed deferasirox (ICL670) FCT for oral use daily. Deferasirox FCT dosing was based on subject's weight. Receives: Drug: Deferasirox |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Selected Gastrointestinal Disorders up to 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). Only descriptive analysis performed.
Measured: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Secondary outcomes (28)
Adverse Events Profile
Analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event TEAEs and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.
Measured: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Number of Participants With Notable Changes in ECG Values From Baseline
Safety measured by the notable post-baseline changes in ECG values (PR, QRS, QT, QTcF and HR intervals) compared to baseline. Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Measured: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Absolute Change From Baseline in Serum Ferritin (SF)
Absolute change from baseline over time in SF values up to 24 weeks of treatment were to be provided. Only descriptive analysis performed.
Measured: Baseline (BL), Week 4, Week 8, Week 12, Week 16, EOT (Week 24)
Number of Participants With Worst Post-baseline Values in Selected Chemistry Parameters
Safety measured by the worst post-baseline severity grade observed in a patient calculated using the normal/low/high classifications based on local laboratory normal ranges, regardless of the baseline status. Baseline was defined as the last non-missing value on or prior to the first dose. The selected chemistry parameters were: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), total bilirubin, direct bilirubin, serum creatinine and Urine protein creatinine ratio (UPCR) (Protein/Creatinine represented UPCR). Only descriptive analysis performed.
Measured: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Number of Participants With Clinically Significant Auditory Assessments Changes From Baseline
Safety measured by notable post-baseline changes in Auditory assessments (comprehensive audiometry threshold examination and speech recognition). Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Measured: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Number of Participants With Clinically Significant Ocular Assessments Changes From Baseline
Safety measured by notable post-baseline changes in Ocular assessments (Distance visual acuity test, Applanation tonometry, lens photography, wide angle fundus photography of the retina and optic nerve). Ocular assessment were required at screening and end of Treatment; during treatment, they were to be performed at the discretion of the investigator based on patient reporting symptoms. Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Measured: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Absolute Change From Baseline in Systolic and Diastolic Blood Pressures (mmHg)
Absolute change from baseline over time in systolic and diastolic blood pressures measurements were to be provided. Only descriptive analysis performed.
Measured: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Absolute Change From Baseline in Pulse Rate (Bpm)
Absolute change from baseline over time in supine pulse rate was to be provided. Only descriptive analysis performed.
Measured: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Absolute Change From Baseline in Body Temperature (°C)
Absolute change from baseline over time in body temperature measurements was to be provided. Only descriptive analysis performed.
Measured: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Absolute Change From Baseline in Body Weight (kg)
Absolute change from baseline over time in body weight measurements was to be provided. Only descriptive analysis performed.
Measured: Baseline (BL), Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Participants Pre-treated With Deferasirox: Mean Change From Baseline in Adherence
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT adherence domain consisted of 6 items from the child's perspective and 6 items from the caregiver's perspective, each with a possible score of 1 to 5, for an overall possible score range of 6 to 30. A higher score indicates poorer adherence. Only descriptive analysis performed.
Measured: Week 4, Week 12, EOT (Week 24)
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Type of Medicine Child Like Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the type of medicine the child said he/she liked best (tablet to dissolve in liquid, tablet (taken once a day), tablet (taken 3 times a day), tablet crushed, sprinkle powder on food, injection and I don't know). These items were presented descriptively using frequency counts.
Measured: Baseline (BL), Week 4, Week 12, EOT (Week 24)
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Reasons Child Preferred Crushed Medicine Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the reason child preferred crushed medicine (taste, aftertaste, convenience, number of pills, no/less side effects, can correctly prepare the medicine, easier to remember to take the medicine, number of times he/she has to take the medicine, no/less pain on the injection site, gain personal time with their family and friends, and other). These items were presented descriptively using frequency counts.
Measured: Baseline (BL), Week 4, Week 12, EOT (Week 24)
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Rank Based on Child's Preference Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the rank of the medicine (tablet to dissolve in liquid, tablet taken once a day, tablet taken 3 times a day, tablet crushed, sprinkle powder on food and injection), with a range of 1 to 6 (1 being most preferred and 6 being least preferred), based on what the child prefers. These items were presented descriptively using frequency count.
Measured: Baseline (BL), Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Participants Pre-treated With Deferasirox: Mean Change From Baseline in Concerns
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT concerns domain scale for child's response had a possible range from 2 to 10, based on two questions and the mSICT concerns domain scale for caregiver's responses had the possible range of 1 to 5 based on one question. A higher score indicated fewer concerns. Only descriptive analysis performed.
Measured: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Mean Change From Baseline in Adherence
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT adherence domain consisted of 6 items from the child's perspective and 6 items from the caregiver's perspective, each with a possible score of 1 to 5, for an overall possible score range of 6 to 30. A higher score indicates poorer adherence. Only descriptive analysis performed.
Measured: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Type of Medicine Child Like Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the type of medicine the child said he/she liked best (tablet to dissolve in liquid, tablet (taken once a day), tablet (taken 3 times a day), tablet crushed, sprinkle powder on food, injection and I don't know). These items were presented descriptively using frequency counts.
Measured: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Reasons Child Preferred Crushed Medicine Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the reason child preferred crushed medicine (taste, aftertaste, convenience, number of pills, no/less side effects, can correctly prepare the medicine, easier to remember to take the medicine, number of times he/she has to take the medicine, no/less pain on the injection site, gain personal time with their family and friends, and other). These items were presented descriptively using frequency counts.
Measured: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Rank Based on Child's Preference Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the rank of the medicine (tablet to dissolve in liquid, tablet taken once a day, tablet taken 3 times a day, tablet crushed, sprinkle powder on food and injection), with a range of 1 to 6 (1 being most preferred and 6 being least preferred), based on what the child prefers. These items were presented descriptively using frequency counts.
Measured: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Mean Change From Baseline in Concerns
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT concerns domain scale for child's response had a possible range from 2 to 10, based on two questions and the mSICT concerns domain scale for caregiver's responses had the possible range of 1 to 5 based on one question. A higher score indicated fewer concerns. Only descriptive analysis performed.
Measured: Week 4, Week 12, EOT (Week 24)
Palatability Score in Chelation Naive Participants
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated separately. Among the taste items, first one measured taste on a five point response scale. The last two items measured what happened after taking the medicine, i.e., swallowed or vomited etc. and how the perceived amount of liquid taken with the medicine was, enough, not enough or too much. The palatability summary score was calculated from these three items using a scoring matrix and the score ranges from 0 to 11. A higher score indicates better palatability. Only descriptive analysis was performed.
Measured: Week 4, Week 12, EOT (Week 24)
Number of Chelation Naive Participants With Palatability After Taste Item Scoring
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated as a separate item and scored on a 5-point response scale with the response format Very good = 1 (best), Good = 2, Neither good nor bad = 3, Bad = 4, Very bad = 5 (worst). Only descriptive analysis performed using frequency counts.
Measured: Week 4, Week 12, EOT (Week 24)
Palatability Score in Participants Pre-treated With Deferasirox
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated separately. Among the taste items, first one measured taste on a five point response scale. The last two items measured what happened after taking the medicine, i.e., swallowed or vomited etc. and how the perceived amount of liquid taken with the medicine was, enough, not enough or too much. The palatability summary score was calculated from these three items using a scoring matrix and the score ranges from 0 to 11. A higher score indicates better palatability. Only descriptive analysis was performed.
Measured: Week 4, Week 12, EOT (Week 24)
Number of Participants Pre-treated With Deferasirox With Palatability After Taste Item Scoring
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated as a separate item and scored on a 5-point response scale with the response format Very good = 1 (best), Good = 2, Neither good nor bad = 3, Bad = 4, Very bad = 5 (worst). Only descriptive analysis performed using frequency counts.
Measured: Baseline, Week 4, Week 12, EOT (Week 24)
GI Symptom Score in Chelation Naive Participants
The GI symptom score was calculated from responses to 5 questions, each with a possible score of 1 to 5, for an overall possible score range of 5 to 25, where a lower score represents a less severe GI symptom and a higher score represents a more severe GI symptom. GI symptom scores were summarized using descriptive statistics at week 2, week 3, week 4, week 8, week 12, week 16, week 20 and EOT.
Measured: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Number of Participants With GI Bowel Movements Item Scoring in Chelation Naive Participants
The GI symptom questionnaire consisted of 6 items, 5 of which were scored using a 1-5 rating scale. The sixth item assessed bowel movement frequency during the past week, using 7 response options 0 = 0 ("None"), 1 = 1, 2 = 2, 3 = 3, 4 = 4, 5 = "5 - 10" and 6 = "11 or more". The GI bowel movements item score was presented descriptively using frequency counts.
Measured: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
GI Symptom Score in Participants Pre-treated With Deferasirox
The GI symptom score was calculated from responses to 5 questions, each with a possible score of 1 to 5, for an overall possible score range of 5 to 25, where a lower score represents a less severe GI symptom and a higher score represents a more severe GI symptom. GI symptom scores were summarized using descriptive statistics at week 2, week 3, week 4, week 8, week 12, week 16, week 20 and EOT.
Measured: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Number of Participants With GI Bowel Movements Item Scoring in Participants Pre-treated With Deferasirox
The GI symptom questionnaire consisted of 6 items, 5 of which were scored using a 1-5 rating scale. The sixth item assessed bowel movement frequency during the past week, using 7 response options 0 = 0 ("None"), 1 = 1, 2 = 2, 3 = 3, 4 = 4, 5 = "5 - 10" and 6 = "11 or more". The GI bowel movements item score was presented descriptively using frequency counts.
Measured: Baseline, Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2017
- Study start16 Jan 2018
- Primary completion5 Dec 2019
- Study completion5 Dec 2019
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 Iron OverloadStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 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
- NCT03372083
- Sponsor's protocol ID
- CICL670F2429
- Other IDs
- 2016-003482-25, 2016
- Acronym
- MIMAS
- Status last verified
- Aug 2020
- First submitted
- 21 Nov 2017
- Last updated
- 25 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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 25 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03372083
- Acronym / sponsor ID
- MIMAS / CICL670F2429
- Conditions
- Iron Overload
- Keywords
- Iron Chelation Therapy, Deferasirox, Asunra, Jadenu, Exjade, ICL 670, Pediatric
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Jan 2018 (actual)
- Primary completion
- 5 Dec 2019 (actual)
- Study completion
- 5 Dec 2019 (actual)
- First posted
- 13 Dec 2017 (actual)
- Results
- Posted 3 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study employed a prospective, single-arm, global multi-center interventional open-label, non-randomized design to identify and assess safety profile of the crushed deferasirox FCT when administered up to 24 weeks in pediatric patients aged ≥2 to <6 years with transfusional hemosiderosis. The study was designed to enroll a minimum of 40 patients. Forty-four patients were treated and analyzed.
Detailed description
The study included a screening period (from Day 0-14) with two visits at least 7 days apart to assess eligibility of patients that were 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) were to occur to determine eligibility. Any current chelation therapy except deferasirox were to be discontinued to undergo a 5-day washout period prior to commencing a 24 week treatment period with crushed deferasirox FCT.
All patients were to have weekly visits for the first month to monitor renal function. Hepatic function were to be assessed biweekly during the first month. Thereafter, monthly safety assessments were to 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.
The planned duration of treatment was 24 weeks followed by a 30-day safety follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Deferasirox | Experimental | Drug: DeferasiroxCrushed deferasirox (ICL670) FCT for oral use daily. Deferasirox FCT dosing was based on subject's weight. |
Who may qualify
- Ages
- 2 to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Patients ≥2 to <6 years old diagnosed with transfusional hemosiderosis
- Documented history of red blood cell transfusions
- 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.
- 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.
- 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.
Key exclusion criteria (18 listed)
- 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.)
- Patients continuing on deferoxamine or deferiprone in addition to study treatment. (Patients switching to or continuing on deferasirox are eligible).
- Unresolved adverse events if the patient was previously treated with deferiprone or deferoxamine or deferasirox.
- 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.
- Serum creatinine > age adjusted ULN measured at any screening visit
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 |
|---|---|---|
| DeferasiroxAlso: ICL670Deferosirox was provided in tablet forms of 90, 180 and 360mg. Tablets were crushed in the home environment and administered by sprinkling the full dose on to soft food to be consumed immediately. | Drug | Deferasirox |
Primary outcome
Number of Participants With Selected Gastrointestinal Disorders up to 24 Weeks
Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
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). Only descriptive analysis performed.
28 secondary outcomes
Adverse Events Profile
Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Number of Participants With Notable Changes in ECG Values From Baseline
Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Absolute Change From Baseline in Serum Ferritin (SF)
Time frame: Baseline (BL), Week 4, Week 8, Week 12, Week 16, EOT (Week 24)
Number of Participants With Worst Post-baseline Values in Selected Chemistry Parameters
Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Number of Participants With Clinically Significant Auditory Assessments Changes From Baseline
Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Number of Participants With Clinically Significant Ocular Assessments Changes From Baseline
Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Absolute Change From Baseline in Systolic and Diastolic Blood Pressures (mmHg)
Time frame: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Absolute Change From Baseline in Pulse Rate (Bpm)
Time frame: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Absolute Change From Baseline in Body Temperature (°C)
Time frame: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Absolute Change From Baseline in Body Weight (kg)
Time frame: Baseline (BL), Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Participants Pre-treated With Deferasirox: Mean Change From Baseline in Adherence
Time frame: Week 4, Week 12, EOT (Week 24)
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Type of Medicine Child Like Scoring
Time frame: Baseline (BL), Week 4, Week 12, EOT (Week 24)
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Reasons Child Preferred Crushed Medicine Scoring
Time frame: Baseline (BL), Week 4, Week 12, EOT (Week 24)
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Rank Based on Child's Preference Scoring
Time frame: Baseline (BL), Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Participants Pre-treated With Deferasirox: Mean Change From Baseline in Concerns
Time frame: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Mean Change From Baseline in Adherence
Time frame: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Type of Medicine Child Like Scoring
Time frame: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Reasons Child Preferred Crushed Medicine Scoring
Time frame: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Rank Based on Child's Preference Scoring
Time frame: Week 4, Week 12, EOT (Week 24)
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Mean Change From Baseline in Concerns
Time frame: Week 4, Week 12, EOT (Week 24)
Palatability Score in Chelation Naive Participants
Time frame: Week 4, Week 12, EOT (Week 24)
Number of Chelation Naive Participants With Palatability After Taste Item Scoring
Time frame: Week 4, Week 12, EOT (Week 24)
Palatability Score in Participants Pre-treated With Deferasirox
Time frame: Week 4, Week 12, EOT (Week 24)
Number of Participants Pre-treated With Deferasirox With Palatability After Taste Item Scoring
Time frame: Baseline, Week 4, Week 12, EOT (Week 24)
GI Symptom Score in Chelation Naive Participants
Time frame: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Number of Participants With GI Bowel Movements Item Scoring in Chelation Naive Participants
Time frame: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
GI Symptom Score in Participants Pre-treated With Deferasirox
Time frame: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Number of Participants With GI Bowel Movements Item Scoring in Participants Pre-treated With Deferasirox
Time frame: Baseline, Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Deferasirox in people with Iron Overload, run by Novartis Pharmaceuticals at 10 sites in 7 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 5 inclusion and 18 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 25 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy, Thailand, Egypt, Lebanon, Oman and 2 more countries. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 3 Aug 2020). 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?
Number of Participants With Selected Gastrointestinal Disorders up to 24 Weeks (time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.). 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 25 Aug 2020.