Clinical trial: A Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis. (NCT03203850)

Eligibility criteria:
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. -
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 51-year-old man comes to the office complaining of fatigue and some sexual problems including lack of libido. The patient doesn't smoke or use any illicit drug.  Blood pressure is 120/80 mm Hg and pulse is 70/min.  Oxygen saturation is 99% on room air.  BMI is 24 kg/m2.  Skin examination shows increased pigmentation. Genotype testing is consistent with homozygosity for the C282Y mutation. Laboratory study shows transferrin saturation of 55% and serum ferritin of 550 μg/L. He is diagnosed as a case of hemochromatosis.

Patient description (patient's own words): I am 51 years old and I just came back from the doctor's office. I'm sick and tired of being that exhausted, reaching the point where me and my lovely wife are not touching each other anymore! I'm not smoking or doing drugs! My blood pressure was 120/80 mm Hg, and pulse was 70/min and my oxygen saturation 99%. My BMI is 24. My skin also turned a bit darker lately. He tested my genes and told me that I have a mutation of the C282Y gene. I also did lab tests where my transferrin saturation was 55% and serum ferritin was 550  μg/L. The doctor diagnosed me with iron overload.

Does the patient match the trial criteria? Entailment