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

NCT03203850 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CICL670F22032016-002529-12
• Study Type: interventional
• Target: 45
• Locations: 7 countries
• Sites: 11

Brief Summary

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.

Conditions

Hereditary Hemochromatosis

Keywords

hereditary hemochromatosis; ICL670; deferasirox FCT; iron overload

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Achieving Target SF ≤ 100 μg/L for the First Time

  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 Outcomes (12)

• Number of Participants With Ocular Treatment Emergent Adverse Events (AEs)

  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

  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)

  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

  Up to 24 months

• Categorical Analysis of logMAR Score Changes From Baseline to Best Post-baseline Changes in One Eye With More Extreme Change

  Baseline, Weeks 24, 52, 76 and 104.

Study Arms (2)

Deferasirox FCT Arm

EXPERIMENTAL

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

phlebotomy

ACTIVE COMPARATOR

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

Interventions

Deferasirox FCT DRUG

Taken orally once per day (QD) as a film coated tablet (FCT)

Also known as: ICL670

Deferasirox FCT Arm

Phlebotomy PROCEDURE

according to investigator's decision

phlebotomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Limoges, 87042, France

Location

Novartis Investigative Site

Rennes, 35043, France

Location

Novartis Investigative Site

Sibiu, 550245, Romania

Location

Novartis Investigative Site

Moscow, 125167, Russia

Location

Novartis Investigative Site

Bratislava, 831 01, Slovakia

Location

Novartis Investigative Site

Bratislava, 85107, Slovakia

Location

Novartis Investigative Site

Manresa, Espana, 08241, Spain

Location

Novartis Investigative Site

Barakaldo, Vizcaya, 48903, Spain

Location

Novartis Investigative Site

Las Palmas de Gran Canaria, 35010, Spain

Location

Novartis Investigative Site

Lugano, 6900, Switzerland

Location

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Hemochromatosis; Iron Overload

Interventions

Deferasirox; Phlebotomy

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

The results should be interpreted with caution due to low number of participants enrolled in both arms.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: June 29, 2017
• Study Start: January 11, 2018
• Primary Completion: April 17, 2023
• Study Completion: April 17, 2023
• Last Updated: October 9, 2024
• Results First Posted: June 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

FR (2); RU (1); CH (1); RO (1); SL (2); ES (3); BE (1)