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A Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis.

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03203850
Recruitment Status : Recruiting
First Posted : June 29, 2017
Last Update Posted : April 22, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 22, 2017
First Posted Date  ICMJE June 29, 2017
Last Update Posted Date April 22, 2020
Actual Study Start Date  ICMJE January 11, 2018
Estimated Primary Completion Date April 21, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2017)
Proportion of patients achieving target SF ≤ 100 μg/L for the first time. [ Time Frame: Response is defined by achieving target SF ≤ 100 μg/L on or before 24 months. ]
Assess the response rate (RR) of deferasirox film coated tablet (FCT) and phlebotomy treatment arms where response is defined by achieving target serum ferritin (SF) ≤ 100 μg/L on or before 24 months. Estimate of the RR and corresponding 95% confidence interval (CI) will be provided for each arm. No formal hypothesis testing is planned in this study.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2017)
  • Incidence of ocular adverse events (AEs) overall [ Time Frame: 24 months ]
    To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by the incidence of treatment-emergent ocular adverse events (AEs) (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.
  • Incidence of ocular adverse events (AEs) by severity [ Time Frame: 24 months ]
    To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by AE severity (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis.
Official Title  ICMJE 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.
Brief Summary

The purpose of this study is to evaluate the efficacy and safety of deferasirox film coated tablet (FCT) versus phlebotomy for the management of iron overload in adults with HH at risk of iron-related morbidity. This evaluation will provide 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hereditary Hemochromatosis
Intervention  ICMJE
  • Drug: Deferasirox FCT
    Taken orally once per day (QD)
    Other Name: ICL670
  • Procedure: Phlebotomy
    according to investigator's decision
Study Arms  ICMJE
  • Experimental: Deferasirox FCT Arm
    randomized in a 2:1 ratio: Deferasirox to surgery
    Intervention: Drug: Deferasirox FCT
  • Experimental: phlebotomy
    randomized in a 2:1 ratio: Deferasirox to surgery
    Intervention: Procedure: Phlebotomy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 28, 2017)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2023
Estimated Primary Completion Date April 21, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Other protocol-defined inclusion/exclusion may apply. -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Romania,   Russian Federation,   Slovakia,   Spain,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03203850
Other Study ID Numbers  ICMJE CICL670F2203
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP