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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03203850

Collaborator

(none)

Enrollment

Locations

Arms

63.2

Anticipated Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hereditary Hemochromatosis	Drug: Deferasirox FCT Procedure: Phlebotomy	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Jan 11, 2018

Anticipated Primary Completion Date :

Apr 18, 2023

Anticipated Study Completion Date :

Apr 18, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferasirox FCT Arm randomized in a 2:1 ratio: Deferasirox to surgery	Drug: Deferasirox FCT Taken orally once per day (QD) Other Names: ICL670
Experimental: phlebotomy randomized in a 2:1 ratio: Deferasirox to surgery	Procedure: Phlebotomy according to investigator's decision

Arm

Intervention/Treatment

Experimental: Deferasirox FCT Arm

randomized in a 2:1 ratio: Deferasirox to surgery

Drug: Deferasirox FCT

Taken orally once per day (QD)

Other Names:

ICL670

Experimental: phlebotomy

randomized in a 2:1 ratio: Deferasirox to surgery

Procedure: Phlebotomy

according to investigator's decision

Outcome Measures

Primary Outcome Measures

Proportion of patients achieving target SF ≤ 100 μg/L for the first time. [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.

Secondary Outcome Measures

Incidence of ocular adverse events (AEs) overall [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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:

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

Concomitant therapy that precludes enrollment:

Prior iron chelation therapy
Prohibited concomitant medications with deferasirox

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

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

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. -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Leuven		Belgium	3000
2	Novartis Investigative Site	Limoges cedex		France	87042
3	Novartis Investigative Site	Rennes		France	35043
4	Novartis Investigative Site	Sibiu		Romania	550245
5	Novartis Investigative Site	Moscow		Russian Federation	125167
6	Novartis Investigative Site	Bratislava		Slovakia	831 01
7	Novartis Investigative Site	Bratislava		Slovakia	85107
8	Novartis Investigative Site	Manresa	Espana	Spain	08241
9	Novartis Investigative Site	Baracaldo	Vizcaya	Spain	48903
10	Novartis Investigative Site	Las Palmas de Gran Canaria		Spain	35010
11	Novartis Investigative Site	Lugano		Switzerland	6900