Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis (HH)

October 7, 2024 updated by: Novartis Pharmaceuticals

A Phase II, Multicenter, Open-label, Randomized Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis.

The purpose of this study was to evaluate the efficacy and safety of deferasirox film coated tablet (FCT) versus phlebotomy for the management of iron overload in adults with Hereditary Hemochromatosis (HH) at risk of iron-related morbidity. This evaluation provided information on the two treatment options in terms of the rate of response of proportion of patients reaching the study target SF ≤ 100 μg/L and their associated safety profiles.

In addition to exploring the safety and efficacy of deferasirox FCT in hereditary hemochromatosis (HH), this study is being conducted to fulfill an FDA post-marketing requirement [PMC 750-10 (Exjade) /PMR 2888-8 (Jadenu)] to provide additional randomized data to confirm the ocular safety profile of deferasirox through detailed ocular assessments in patients treated with deferasirox FCT for 2 years.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This was a Phase II, multicenter, open-label, randomized two-year study in adults with Hereditary Hemochromatosis (HH) confirmed by HH genotype with iron overload. Eligible subjects were identified during a 4-week screening period, then randomized in a 2:1 ratio to be treated with deferasirox FCT or phlebotomy for up to 24 months (104 weeks).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • France
      • Limoges cedex, France, 87042
        • Novartis Investigative Site
      • Rennes, France, 35043
        • Novartis Investigative Site
  • Romania
      • Sibiu, Romania, 550245
        • Novartis Investigative Site
  • Russian Federation
      • Moscow, Russian Federation, 125167
        • Novartis Investigative Site
  • Slovakia
      • Bratislava, Slovakia, 85107
        • Novartis Investigative Site
      • Bratislava, Slovakia, 831 01
        • Novartis Investigative Site
  • Spain
      • Las Palmas de Gran Canaria, Spain, 35010
        • Novartis Investigative Site
    • Espana
      • Manresa, Espana, Spain, 08241
        • Novartis Investigative Site
    • Vizcaya
      • Baracaldo, Vizcaya, Spain, 48903
        • Novartis Investigative Site
  • Switzerland
      • Lugano, Switzerland, 6900
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Written informed consent must be obtained prior to any screening procedures.

Patients eligible for inclusion must meet all following criteria prior to receiving study treatment:

1. Male or female ≥ 18-years-old 2. Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) 3. Transferrin saturation ≥ 45% (at either screening visit) 4. Serum ferritin (SF) ≥ 500 μg/L (at either screening visit)

-

Exclusion Criteria:

  1. Medical conditions that preclude inclusion:

    • Iron overload not due to HH
    • Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox
    • Systemic disease which prevents taking study treatment or any contraindication to phlebotomy
    • Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia
    • Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection.
    • Psychiatric or addictive disorder which prevent giving informed consent or undergoing any of the treatment options or unwilling or unable to comply with the protocol
    • Uncontrolled or significant cardiac disease or symptomatic cardiac arrhythmias, e.g., sustained ventricular tachycardia and clinically significant second or third degree AV block without a pacemaker.
    • Illicit drug use and/or alcohol use, defined as an average alcohol consumption greater than one standard drink a day for women or two standard drinks a day for men within the 12 months prior to enrolment. A standard drink is generally considered to be 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof distilled spirits
    • Cirrhosis, including Child-Pugh class A, B, and C, diagnosed by liver biopsy, elastography, radiologic exams, or clinical criteria
    • Active hepatitis B or C (hepatitis B carrier will be allowed)
    • History of HIV seropositivity (ELISA or Western blot)
    • Organ transplant recipient
    • Malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, except localized basal cell carcinoma of the skin, or any history of hepatocellular carcinoma

  2. Concomitant therapy that precludes enrollment:

    • Prior iron chelation therapy
    • Prohibited concomitant medications with deferasirox

  3. Abnormal Laboratory Values:

    • Significant anemia that contraindicates phlebotomy (males with hemoglobin < 130g/L, females with hemoglobin < 120g/L) in both screening visit samples
    • Platelets ≤ 50 x 109/L in both screening visit samples
    • Urine protein/urine creatinine ratio > 1.0 mg/mg in both non-first void urine screening visit samples
    • Creatinine clearance ≤ 40 ml/min, or use the locally approved contraindication limit in prescribing information if it is stricter, in both screening visit samples
    • Serum creatinine > 1.5 x ULN in both screening visit samples
    • ALT ≥ 5 x ULN in both screening visit samples
    • Total bilirubin > 1.5 x ULN in both screening visit samples

  4. Participation in an investigational study:

    • Observational registry study is allowable
    • Within 30 days prior to enrollment or within 5-half-lives of an investigational product, whichever is longer
    • Treatment with a systemic investigational drug within 4 weeks or topical investigational drug within 7 days of starting the study

  5. Pregnancy and contraception:

    • Pregnant or nursing (lactating) women
    • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless using basic methods of contraception, such as:
    • Total abstinence Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are unacceptable methods.
    • Female sterilization (bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. If oophorectomy alone, hormone levels must confirm menopause.
    • Male sterilization (at least 6 months prior to screening). The vasectomized male must be the sole partner.
    • Barrier methods of contraception: condom or occlusive cap For UK: spermicidal foam/gel/film/cream/vaginal suppository
    • Placement of an intrauterine device or intrauterine system
    • Women considered as post-menopausal and not of childbearing potential are allowed to be enrolled in the trial if they have had 12 months of natural (spontaneous) amenorrhea with an expected clinical profile, e.g., age appropriate and history of vasomotor symptoms.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Deferasirox FCT Arm
An initial dose of deferasirox FCT 7 mg/kg/day was used for 3 months (12 weeks), then was adjusted according to the serum ferritin (SF) level. Deferasirox was interrupted when the study-defined target SF ≤ 100 μg/L was achieved. Deferasirox was to be reinitiated when SF ≥ 300 μg/L, according to deferasirox label.
Drug: Deferasirox FCT
Taken orally once per day (QD) as a film coated tablet (FCT)
Other Names:
  • ICL670
Active Comparator: phlebotomy
Phlebotomy was conducted at a frequency determined by the physician. Phlebotomy was interrupted when the study-defined target SF ≤ 100 μg/L was achieved. Phlebotomy was to be reinitiated when SF > 100 μg/L, based on standard of care practice.
Procedure: Phlebotomy
according to investigator's decision

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of Patients Achieving Target SF ≤ 100 μg/L for the First Time
Time Frame: Up to Month 24
Proportion of participants achieving target serum ferritin (SF) ≤ 100 μg/L on or before Month 24. Participants were considered responders if they met response criteria (target SF ≤100 µg/L) on or before Month 24 (Week 104) during the treatment phase. Any participant who discontinued treatment prematurely before meeting such criterion and participants with unknown or missing SF by Month 24 were counted as non-responder.
Up to Month 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Ocular Treatment Emergent Adverse Events (AEs)
Time Frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 108 weeks.
Number of participants with at least one ocular treatment emergent adverse event (new or worsening from baseline).
Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 108 weeks.
Number of Participants With Ocular Treatment Emergent Adverse Events (AEs) by Preferred Term
Time Frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 108 weeks.
Number of participants with at least one ocular treatment emergent adverse event (new or worsening from baseline). Preferred terms are based on Medical Dictionary of Regulatory Activities (MedDRA) version 26.0.
Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 108 weeks.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 108 weeks.
Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs leading to study treatment discontinuation, and SAEs.
Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 108 weeks.
Number of Adverse Events in Participants Who Had Study Treatment Interrupted Due to SF ≤ 100 μg/L and Re-initiated Study Treatment When ≥ 300 μg/L
Time Frame: Up to 24 months

Number of participants with Adverse Events who interrupt deferasirox FCT at least once due to SF level ≤ 100 μg/L and re-initiate therapy at SF level ≥ 300 μg/L.

There were no participants that re-initiated therapy when reached 300 ug/L.
Up to 24 months
Categorical Analysis of logMAR Score Changes From Baseline to Best Post-baseline Changes in One Eye With More Extreme Change
Time Frame: Baseline, Weeks 24, 52, 76 and 104.
Visual acuity was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. A letter score was calculated based on the number of letters that could correctly be identified from specified distances. For low luminance and standard acuity measures, visual acuity was described on a logMAR scale for all measures. For including acuity obtained with the ETDRS letter score, the values were converted to a logMAR scale, using the following formula: logMAR = 1.7-0.02*ETDRS score. With this conversion, a difference from baseline of 0.1 logMAR = 5-letter difference in visual acuity, 0.2 logMAR = 10-letter difference, 0.3 logMAR = 15-letter difference, 0.4 logMAR = 20-letter difference, 0.5 logMAR = 25-letter difference and 0.6 logMAR = 30-letter difference. Decrease in logMAR score category from baseline indicates improvement in visual acuity. The best change from baseline amongst all post baseline visit is presented.
Baseline, Weeks 24, 52, 76 and 104.
Categorical Analysis of logMAR Score Changes From Baseline to Worst Post-baseline Changes in One Eye With More Extreme Change
Time Frame: Baseline, Weeks 24, 52, 76 and 104.
Visual acuity was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. A letter score was calculated based on the number of letters that could correctly be identified from specified distances. For low luminance and standard acuity measures, visual acuity was described on a logMAR scale for all measures. For including acuity obtained with the ETDRS letter score, the values were converted to a logMAR scale, using the following formula: logMAR = 1.7-0.02*ETDRS score. With this conversion, a difference from baseline of 0.1 logMAR = 5-letter difference in visual acuity, 0.2 logMAR = 10-letter difference, 0.3 logMAR = 15-letter difference, 0.4 logMAR = 20-letter difference, 0.5 logMAR = 25-letter difference and 0.6 logMAR = 30-letter difference. Increase in logMAR score from baseline indicates worsening in visual acuity. The worst change from baseline amongst all post baseline visit is presented.
Baseline, Weeks 24, 52, 76 and 104.
Categorical Analysis of Worst Post-baseline Values of Intraocular Pressure in One Eye With More Extreme Change
Time Frame: Weeks 24, 52, 76 and 104
Intraocular pressure was measured by tonometry. Intraocular pressure values >5 to ≤21 mmHg were considered normal. The worst post-baseline value corresponds to the worst outcome amongst all post baseline visit
Weeks 24, 52, 76 and 104
Categorical Analysis of Changes in Intraocular Pressure From Baseline to Best/Worst Post-baseline Changes in One Eye With More Extreme Change
Time Frame: Baseline, up to Week 104
Intraocular pressure was measured by tonometry. A decrease in intraocular pressure from baseline indicated improvement.
Baseline, up to Week 104
Number of Participants With Slit Lamp Results for Any Evaluation and Worst Eye
Time Frame: Baseline, up to Week 104
Slit lamp examination was used to evaluate lids, cornea, conjunctiva, iris, anterior chamber, aqueous flare, aqueous inflammatory cells and lens. Any post-baseline abnormalities (not present at baseline) in slit lamp examination were assesses by the investigator and classified as insignificant or clinically significant. Number of participants with slit lamp results (normal, insignificant, significant, missing) for any evaluation and worst eye are reported.
Baseline, up to Week 104
Number of Participants With an Increase From Baseline of ≥1 and ≥2 in LOCS III Grades
Time Frame: Baseline, up to Week 104

Lens Opacities Classification System III (LOCS III) grading scales include lens opacities defined as nuclear opalescence (NO), nuclear color (NC), cortical (C) cataract and posterior subcapsular (P) cataract with several degrees of extend, i.e. severity. The LOCS III scale for nuclear opalescence and for nuclear color ranges from 0 to 6. The LOCS III scale for cortical cataract and posterior subcapsular cataract opacity ranges from 0 to 5. For all scales, higher values indicate higher opacity, opalescence, or color (range: NO0/NC0/C0/P0 to NO6/NC6/C5/P5).

Number of participants with an increase from baseline of ≥1 and increase of ≥2 in LOCS III grades is reported.
Baseline, up to Week 104
Number of Participants With Fundus Oculi Results for Any Evaluation and Worst Eye
Time Frame: Baseline, up to Week 104
Fundus oculi examination was used to evaluate peripheral retina, macula, optic nerve, and vitreous hemorrhage. Any post-baseline abnormalities (not present at baseline) in fundus oculi examination were assessed by the investigator and classified as insignificant or clinically significant. Number of participants with fundus oculi results (normal, insignificant, significant, missing) for any evaluation and worst eye are reported.
Baseline, up to Week 104
Time to Response (TTR)
Time Frame: Up to Month 24
Time to response (TTR) is defined as the time from the date of randomization to the date of the first time the SF achieved a value ≤ 100 μg/L during the treatment phase. Participants who did not achieve SF ≤ 100 μg/L were censored as follows: at the last serum ferritin assessment date on or before month 24 (week 104), at the day of randomization if a subject does not have any post-baseline serum ferritin value or at the death date. TTR was analyzed using the Kaplan-Meier method.
Up to Month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 11, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 17, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 17, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 22, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 28, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 29, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CICL670F2203
  • 2016-002529-12 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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