Transfusion-dependent AnemiaPhase 2NCT02435212
Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients (2-<18 Years Old) With Iron Overload
A Phase 2 study testing Deferasirox granule formulation and Deferasirox DT formulation in people with Transfusion-dependent Anemia, run by Novartis Pharmaceuticals at 43 sites in 17 countries.
Trial summary
This was a randomized, open-label, multicenter, two arm, phase II study to evaluate treatment compliance and change in serum ferritin of a deferasirox granule formulation and a deferasirox dispersible tablet (DT) formulation in children and adolescents aged ≥ 2 and < 18 years at enrolment with any… Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Transfusion-dependent Anemia
- What is being tested?
- Deferasirox granule formulation and Deferasirox DT formulation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 43 sitesin 17 countries
- Study dates
- 21 Oct 2015to 15 Jan 2024
- Phase
- Phase 2
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 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Written informed consent/assent before any study-specific procedures. Consent will be obtained from parent(s) or legal guardians. Investigators will also obtain assent of patients according to local guidelines.
- Male and female children and adolescents aged ≥ 2 and < 18 years. [France: Male and female children and adolescent aged ≥ 2 and < 18 years old, however children aged ≥ 2 and ≤ 6years can be enrolled only when deferoxamine treatment is contraindicated or inadequate in these patients as per investigator decision. Applicable to core phase only. Once in the core phase patients can turn 18 years and still be considered eligible, also for participation in the optional extension phase.
- Any transfusion-dependent anemia associated with iron overload requiring iron chelation therapy and with a history of transfusion of approximately 20 PRBC units and a treatment goal to reduce iron burden (300mL PRBC = 1 unit in adults whereas 4 ml/kg PRBC is considered 1 unit for children).
- Serum ferritin > 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).
- Patient has to have participated and completed the 48 weeks core phase treatment as per protocol (For optional extension phase eligibility only).
Who cannot join
- Creatinine clearance below the contraindication limit in the locally approved prescribing information (using Schwartz formula) at screening visit 1 or screening visit 2.
- Serum creatinine > 1.5 xULN at screening measured at screening Visit 1 and or screening Visit 2
- ALT and/or AST > 3.0 x ULN at screening visit 1 or screening visit 2..
- Liver disease with severity of Child-Pugh class B or C.
- Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a second morning urine sample at screening Visit 1 or screening Visit 2.
- Patients with significant impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
- Direct (conjugated) bilirubin >2 x ULN at screening visit 1 or screening visit 2.
- Local access to new formulation (granules or FCT) is available (For optional extension phase eligibility only).
Trial locations and contacts
43 sites in 17 countries.
43 sites in 17 countries
United States13 sites
Novartis Investigative Site
Atlanta, Georgia, 30342
Medical Uni of South Carolina Medical Uni of South Carolina
Charleston, South Carolina, 29425
Novartis Investigative Site
Charleston, South Carolina, 29425
Novartis Investigative Site
Chicago, Illinois, 60611
Novartis Investigative Site
Memphis, Tennessee, 38105
St. Jude Children's Research Hospital Memphis St Jude
Memphis, Tennessee, 38105
Novartis Investigative Site
New York, New York, 10021
Weill Cornell Medical College SC -
New York, New York, 10021
Novartis Investigative Site
Oakland, California, 94609-1809
Childrens Hospital of Philadelphia Onc. Dept
Philadelphia, Pennsylvania, 19104 4399
Novartis Investigative Site
Philadelphia, Pennsylvania, 19104 4399
Childrens Hospital at Montefiore
The Bronx, New York, 10467
Novartis Investigative Site
The Bronx, New York, 10467
Italy4 sites
Novartis Investigative Site
Genova, GE, 16128
Novartis Investigative Site
Naples, 80132
Novartis Investigative Site
Palermo, PA, 90127
Novartis Investigative Site
Palermo, PA, 90146
Malaysia4 sites
Novartis Investigative Site
Ipoh, Perak, 30450
Novartis Investigative Site
Kuala Lumpur, 50589
Novartis Investigative Site
Kuching, Sarawak, 93586
Novartis Investigative Site
Pulau Pinang, 10990
Bulgaria3 sites
Novartis Investigative Site
Plovdiv, 4002
Novartis Investigative Site
Sofia, 1527
Novartis Investigative Site
Varna, 9010
Turkey (Türkiye)3 sites
Novartis Investigative Site
Adana, 01330
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Izmir, 35040
Belgium2 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Edegem, Antwerpen, 2650
France2 sites
Novartis Investigative Site
Créteil, 94000
Novartis Investigative Site
Paris, 75015
Philippines2 sites
Novartis Investigative Site
Quezon, 1100
Novartis Investigative Site
Quezon City, 1100
Thailand2 sites
Novartis Investigative Site
Bangkok Noi, Bangkok, 10700
Novartis Investigative Site
Muang, Chiangmai, 50200
Panama1 site
Novartis Investigative Site
Panama City, Republica de Panama, 0801
About this study
Official title: A Randomized, Open-label, Multicenter, Two Arm, Phase II Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients With Iron Overload
This was a randomized, open-label, multicenter, two arm, phase II study to evaluate treatment compliance and change in serum ferritin of a deferasirox granule formulation and a deferasirox dispersible tablet (DT) formulation in children and adolescents aged ≥ 2 and < 18 years at enrolment with any transfusion-dependent anemia requiring chelation therapy due to iron overload, to demonstrate the effect of improved compliance on iron burden.
Randomization was stratified by age groups (2 to <10 years, 10 to <18 years) and prior iron chelation therapy (Yes/ No). There were two study phases which include a 1 year core phase where participants were randomized to a 48 week treatment period to either Deferasirox DT or granules, and an optional extension phase where all participants received the granules up to 5 years. Participants who demonstrated benefit to granules or DT in the core phase, and/or expressed the wish to continue in the optional extension phase on granules, were offered this possibility until there was local access to the new formulation (granules or film-coated tablet (FCT)) or up to 5 years, whichever occurred first.
- Conditions
- Transfusion-dependent Anemia
- Being tested
- Deferasirox granule formulation, Deferasirox DT formulation
- Keywords
- New formulation, deferasirox, chelation, iron overload, compliance, satisfaction, palatability, PRO, PK, safety, PK/PD, ICL670
- Medical subject headings
- Iron Overload, Patient Compliance, Personal Satisfaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deferasirox granule formulationDrug
Also called ICL670
Deferasirox granules will be provided as stick packs containing 90 mg, 180 mg and 360 mg granules for oral use and will be administered based on body weight.
Deferasirox DT formulationDrug
Also called ICL670
Deferasirox DT will be provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use and will be administered based on body weight.
| Study group | Role | What they receive |
|---|---|---|
| DFX DT | Active comparator | Participants will be administered deferasirox dispersible tablets orally once daily based on body weight for 48 weeks. Receives: Drug: Deferasirox DT formulation |
| DFX Granule | Experimental | Participants will be administered deferasirox granules orally once daily in the form of stick packs based on body weight for 48 weeks. Receives: Drug: Deferasirox granule formulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Overall Compliance Using Stick Pack or Tablet Counts in Iron Chelation Therapy (ICT)-naïve Participants During the Core Phase
Compliance was calculated as the ratio of total count consumed to total count prescribed of deferasirox granule stick packs or dispersible tablets, where total count consumed was derived from cumulative dispensed, returned and lost/wasted counts over 24 weeks of treatment and total count prescribed was derived from cumulative prescribed count over 24 weeks of treatment.
Measured: 24 weeks
Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in ICT naïve Participants During the Core Phase
The analysis included the comparison of means between the two treatment arms of change from baseline after 24 weeks of treatment in serum ferritin in pediatric ICT naïve participants with iron overload. The endpoint was assessed at Week 25 visit.
Measured: From Baseline to Week 25
Secondary outcomes (15)
Percentage of Overall Compliance Using Stick Pack or Tablet Counts in ICT-naïve Participants During the Core Phase
Compliance was calculated as the ratio of total count consumed to total count prescribed of deferasirox granule stick packs or dispersible tablets over 48 weeks of treatment.
Measured: 48 weeks
Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in ICT naïve Participants During the Core Phase
The analysis included the comparison of means between the two treatment arms of change from baseline after 48 weeks of treatment in serum ferritin in pediatric ICT naïve participants with iron overload.
Measured: From Baseline to 48 weeks
Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in Pre-treated Participants During the Core Phase
The analysis included the comparison of means between the two treatment arms of change from baseline after 25 weeks and after 48 weeks of treatment in serum ferritin in pre-treated participants. The analyses were performed at Week 25 and Week 48.
Measured: From Baseline to Week 25 and Week 48
Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Patient Reported Outcomes (PRO) Questionnaires
Participants aged between 10 years and less than 18 years at enrollment completed PRO questionnaires by themselves. The mSICT questionnaire for PRO consisted of 3 domains: adherence, satisfaction/preference, and concerns. The adherence domain had a minimum score of 6 and maximum score of 30; a lower score for adherence indicates better adherence. Satisfaction/preference domain had a minimum score of 2 and maximum score of 10; a lower score for satisfaction/preference indicates better satisfaction/preference. Concerns domain had a minimum score of 3 and maximum score of 15; a higher score for concerns indicate fewer concerns.
Measured: At Week 2, Week 3, Week 25 and Week 48
Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Observer Reported Outcomes (ObsRO) Questionnaire (Caregiver's Perspective)
The ObsRO questionnaires for participants aged between 2 years and less than 10 years were designed as observations made by caregivers such as the parent or legal guardian. The caregivers continued completing the ObsRO questionnaires even after the participant turned 10 years for consistency in responses. The mSICT questionnaire consisted of 2 domains: adherence and concerns per caregiver's perspective. The adherence domain had a minimum score of 5 and a maximum score of 25; a lower score for adherence indicates better adherence. The concerns domain had a minimum score of 1 and a maximum score of 5; a higher score for concerns indicates fewer concerns.
Measured: At Week 2, Week 3, Week 25 and Week 48
Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Observer Reported Outcomes (ObsRO) Questionnaire (Child's Perspective)
The ObsRO questionnaires for participants aged between 2 years and less than 10 years were designed as observations made by caregivers such as the parent or legal guardian. The caregivers continued completing the ObsRO questionnaires even after the participant turned 10 years for consistency in responses. The mSICT questionnaire is presented for 2 domains: adherence and concerns per child's perspective. The adherence domain had a minimum score of 6 and a maximum score of 30; a lower score for adherence indicates better adherence. The concerns domain had a minimum score of 2 and a maximum score of 10; a higher score for concerns indicates fewer concerns.
Measured: At Week 2, Week 3, Week 25 and Week 48
Change Over-time in Domain Score of Palatability Using Patient Reported Outcomes (PRO) Questionnaires
The palatability questionnaire was used to measure: taste, aftertaste, whether medication was taken and how the participant perceived the amount of medication taken. This questionnaire had a minimum score of 0 and maximum score of 11; a higher score means better palatability. Participants aged between 10 years and less than 18 years at enrollment completed the PRO questionnaire by themselves.
Measured: At Week 2, Week 3, Week 25 and Week 48
Change Over-time in Domain Score of Palatability Using Observer Reported Outcomes (ObsRO) Questionnaire
The palatability questionnaire was used to measure: taste, aftertaste, whether medication was taken and how the participant perceived the amount of medication taken. This questionnaire had a minimum score of 0 and maximum score of 11; a higher score means better palatability. The ObsRO questionnaires for participants aged between 2 years and less than 10 years were designed as observations made by caregivers such as the parent or legal guardian. The caregivers continued completing the ObsRO questionnaires even after the participant turned 10 years for consistency in responses.
Measured: At Week 2, Week 3, Week 25 and Week 48
Change Over Time in Weekly Dose Violation Rate Using Compliance Patient Reported Outcomes (PRO) Questionnaire
The compliance questionnaire consisted of 2 items: 1. To assess if the medication was taken (yes/no) and 2. To record of the time when the medication was taken (with a not applicable option for participants who did not take their medication). Daily diary records were used to calculate the rate of dose violation in each study arm (doses missed completely or not taken before 12 PM). The dose violation rate was calculated as:
[Number of dose violations / Drug exposure (days)] *100. Higher values represent more dose violations.
Measured: At Week 1, Week 13, Week 25, Week 37 and Week 48
Change Over Time in Weekly Dose Violation Rate Using Compliance Observer Reported Outcomes (ObsRO) Questionnaire
The compliance questionnaire consisted of 2 items: 1. To assess if the medication was taken (yes/no) and 2. To record the time when the medication was taken (with a not applicable option for participants who did not take their medication). Daily diary records were used to calculate the rate of dose violation in each treatment arm (doses missed completely or not taken before 12 PM). The ObsRO questionnaires for participants aged between 2 years and less than 10 years were designed as observations made by caregivers such as the parent or legal guardian. The caregivers continued completing the ObsRO questionnaires even after the participant turned 10 years for consistency in responses. The dose violation rate was calculated as: [Number of dose violations / Drug exposure (days)] *100.
Higher values represent more dose violations.
Measured: At Week 1, Week 13, Week 25, Week 37 and Week 48
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Core Phase
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
Measured: From Baseline to 48 weeks
Pre-dose Concentrations of Deferasirox to Support the Assessment of Compliance
Pre-dose pharmacokinetic (PK) data from participants in the Pharmacokinetic Analysis Set 1 (PAS-1) were analyzed to assess variability of individual participant's compliance. A linear mixed effect power model to pre-dose samples which fulfill compliance criteria in terms of steady state (4 consecutive same doses prior to the PK sample drawn), time-windows (PK sample drawn 20 to 28 hours after previous dose) and without any vomiting episodes within the 4 hours prior to the PK sample were fitted. The model considered dose, treatment group, stratification factors and potential other factors, such as body weight as covariates.
Measured: At Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, and 45
Concentrations of Deferasirox Between 2 and 4 Hours Post-dose at Weeks 5 and 9
Post-dose pharmacokinetic (PK) data from participants in the Pharmacokinetic Analysis Set 1 (PAS-1) were analyzed along with Pre-dose PK data.
Measured: At Week 5 and Week 9
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Entire Granule Period
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation after participant providing written informed consent for participation in the study. In the DFX Granules arm, AEs are reported since the initial randomization to the arm in the core phase and continuing in the extension phase. In the DFX cross-over arm, AEs are reported for participants since the participant crossed-over from dispersible tablet to granules in the extension phase only.
Measured: From Baseline to 305 weeks
Number of Participants With Adverse Events of Special Interest (AESI) During the Entire Granule Period
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation after participant providing written informed consent for participation in the study. In the DFX Granules arm, AEs are reported since the initial randomization to the arm in the core phase and continuing in the extension phase. In the DFX cross-over arm, AEs are reported for participants since the participant crossed-over from dispersible tablet to granules in the extension phase only. AESI included active monitoring for renal toxicity; including renal failure, hepatic toxicity; including hepatic failure, and gastrointestinal hemorrhage
Measured: From Baseline to 305 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2015 (estimated)
- Study start21 Oct 2015
- Primary completion31 May 2018
- Study completion15 Jan 2024
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 Transfusion-dependent AnemiaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 224 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
- NCT02435212
- Sponsor's protocol ID
- CICL670F2202
- Other IDs
- 2013-004739-55
- Status last verified
- Aug 2024
- First submitted
- 17 Mar 2015
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- 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