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TerminatedNCT02443545Updated Jan 10, 2024Results posted

Long-term Safety and Efficacy of Ferriprox® in Iron Overloaded Patients With Sickle Cell Disease or Other Anemias

A Phase 4 interventional study of Deferiprone in Iron Overload, Sickle Cell Disease and Other Anemias, sponsored by ApoPharma. Terminated at 13 sites in 5 countries. Open to participants aged 3 Years and older. Per ClinicalTrials.gov, last updated 2024-01-10.

Sponsored by ApoPharma · Phase 4, Interventional, and Treatment

Why this study was terminated
Recommendation by DSMB, which felt that sufficient data had been obtained
Phase
Phase 4
Study type
Interventional
Enrollment
134
Allocation
Randomized
Ages
3 Years and older
Sex
All
01

Study summary

This is a long-term follow-up to an earlier study, LA38-0411. Its purpose is to gather more information about the safety and efficacy of deferiprone in patients with sickle cell disease or other anemias who suffer from iron overload caused by regular blood transfusions.

Read the detailed description

Deferiprone (brand name Ferriprox®) is an iron chelator that is approved in the United States and over 60 other countries for the treatment of iron overload in patients with thalassemia, when other treatments are inadequate. This study has been designed to evaluate the long-term efficacy, safety, and tolerability of deferiprone to treat iron overload in patients who have sickle cell disease or other anemias.

Only patients who have completed an earlier study, LA38-0411, are eligible to enroll in this one.

02

Conditions studied

  • Iron Overload
  • Sickle Cell Disease
  • Other Anemias

Keywords

  • Iron overload
  • Sickle cell disease
  • Deferiprone
  • Ferriprox
  • Iron chelation
03

Who can participate

Ages eligible
3 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Completed study LA38-0411

  2. Females of childbearing potential must have a negative pregnancy test result at Visit 1. In addition, if applicable, they must:

    • Use an effective method of contraception according to local requirements, during the study and within 30 days following their last dose of study medication, OR
    • Have had a tubal ligation (supporting evidence required), OR
    • Have had a hysterectomy (supporting evidence required), OR
    • Participate in a non-heterosexual lifestyle, OR
    • Have a male sexual partner who has been sterilized (supporting evidence required)
  3. Fertile heterosexual males and/or their partners must agree to use an effective method of contraception during the study and for 30 days following the last dose of study medication
  4. All patients and/or their authorized legal representatives must provide signed and dated written informed consent prior to the first study intervention, and assent will be obtained from patients who are considered to be minors. Patients must be able to adhere to study restrictions, appointments, and evaluation schedules.

Exclusion criteria

Exclusion Criteria:

  1. Plan to participate in another clinical trial at any time from the day of enrollment until 30 days post-treatment in the current study
  2. For only those patients who were treated with deferoxamine in study LA38-0411 (Group 2): Presence of any medical condition (including clinically significant laboratory abnormalities, such as ALT (alanine aminotransferase) ≥ 5 x ULN or creatinine ≥ 2 x ULN), psychological condition, or psychiatric condition which in the opinion of the investigator would cause participation in the study to be unwise.
  3. Pregnant, breastfeeding, or planning to become pregnant during the study period.
  4. Treatment failure after 1 year on deferiprone which in the investigator's judgment indicates the need for the patient to be started on a different iron chelator
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
134 participants (actual)

Study arms

  • Experimental
    Group 1: Deferiprone 3 years

    Patients in this group are those who were randomized to the deferiprone arm in study LA38-0411, and hence will receive deferiprone for a total of 3 years (1 year in the initial study plus 2 years in the extension study).

    Drug: Deferiprone

  • Experimental
    Group 2: Deferiprone 2 years

    Patients in this group are those who were randomized to the deferoxamine arm in study LA38-0411, and hence will receive deferiprone for 2 years (both of them in the extension study).

    Drug: Deferiprone

Interventions

  • DrugDeferiprone

    Also known as: Ferriprox tablets, Ferriprox oral solution

05

What researchers measure

Primary outcomes

  1. Number of Patients With Adverse Events

    Number of patients with at least one adverse event (AE) of any type; number of patients with at least one serious adverse event, and number of patients who withdrew from the study due to an AE

    Time frame: From the first day of the study until the last study visit (Week 104 or early termination)

Secondary outcomes

  1. Change From Baseline in Liver Iron Concentration (LIC)

    LIC was measured by MRI, in units of mg of iron per gram of liver (dry weight). The change from baseline in LIC was determined for three different periods of exposure to deferiprone: one year, two years, and three years.

    Time frame: One year, two years, and three years after the start of deferiprone therapy

  2. Change From Baseline in Cardiac MRI T2*

    The change from baseline in cardiac MRI T2\* was determined for three different periods of exposure to deferiprone: one year, two years, and three years

    Time frame: One year, two years, and three years after the start of deferiprone therapy

  3. Change From Baseline in Serum Ferritin

    The change from baseline in serum ferritin (SF) was determined for three different periods of exposure to deferiprone: one year, two years, and three years.

    Time frame: One year, two years, and three years after the start of deferiprone therapy

06

Results

Posted Jan 10, 2024
Limitations and caveats
The trial was terminated early upon recommendation of the Data and Safety Monitoring Board (DSMB), which felt that sufficient information had been obtained.

Participant flow

Participant flow — Overall Study
MilestoneGroup 1: Deferiprone 3 YearsGroup 2: Deferiprone 2 Years
Started8945
Completed5026
Not completed3919
Withdrew: Adverse event11
Withdrew: Lost to follow-up02
Withdrew: Physician decision30
Withdrew: Protocol violation81
Withdrew: Pregnancy11
Withdrew: Withdrawal by subject63
Withdrew: Termination of study2011

Outcome measures

PrimaryNumber of Patients With Adverse Events

Number of patients with at least one adverse event (AE) of any type; number of patients with at least one serious adverse event, and number of patients who withdrew from the study due to an AE

Time frame:
From the first day of the study until the last study visit (Week 104 or early termination)
Reported as:
Count of participants · Participants
Number of Patients With Adverse Events
ParticipantsDeferiprone
Number of patients with any type of adverse event104
Number of patients with a serious adverse event35
Number of patients who discontinued due to an AE2
SecondaryChange From Baseline in Liver Iron Concentration (LIC)

LIC was measured by MRI, in units of mg of iron per gram of liver (dry weight). The change from baseline in LIC was determined for three different periods of exposure to deferiprone: one year, two years, and three years.

Time frame:
One year, two years, and three years after the start of deferiprone therapy
Reported as:
Mean · mg of iron per gram of liver dry weight
Change From Baseline in Liver Iron Concentration (LIC)
mg of iron per gram of liver dry weightDeferiprone
Change from baseline in LIC after 1 year-2.64 ± 4.64
Change from baseline in LIC after 2 years-3.91 ± 6.38
Change from baseline in LIC after 3 years-6.64 ± 7.72
Statistical analysis
  • Deferiprone · t-test, 2 sided · p = 0.0000
  • Deferiprone · t-test, 2 sided · p = 0.0000
  • Deferiprone · t-test, 2 sided · p = 0.0000
SecondaryChange From Baseline in Cardiac MRI T2*

The change from baseline in cardiac MRI T2\* was determined for three different periods of exposure to deferiprone: one year, two years, and three years

Time frame:
One year, two years, and three years after the start of deferiprone therapy
Reported as:
Mean · milliseconds
Change From Baseline in Cardiac MRI T2*
millisecondsDeferiprone
Change from baseline in cardiac iron after 1 year1.02 ± 19.65
Change from baseline in cardiac iron after 2 years1.00 ± 21.18
Change from baseline in cardiac iron after 3 years0.98 ± 24.53
Statistical analysis
  • Deferiprone · t-test, 2 sided · p = 0.3146
  • Deferiprone · t-test, 2 sided · p = 0.9454
  • Deferiprone · t-test, 2 sided · p = 0.4336
SecondaryChange From Baseline in Serum Ferritin

The change from baseline in serum ferritin (SF) was determined for three different periods of exposure to deferiprone: one year, two years, and three years.

Time frame:
One year, two years, and three years after the start of deferiprone therapy
Reported as:
Mean · micrograms per liter
Change From Baseline in Serum Ferritin
micrograms per literDeferiprone
Change from baseline in SF after 1 year-1 ± 1986
Change from baseline in SF after 2 years-771 ± 2171
Change from baseline in SF after 3 years-1016 ± 3617
Statistical analysis
  • Deferiprone · t-test, 2 sided · p = 0.9952
  • Deferiprone · t-test, 2 sided · p = 0.0008
  • Deferiprone · t-test, 2 sided · p = 0.0420

Adverse events

Collected over Baseline to end of study (up to 2 years). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Deferiprone1/134 (0.7%)35/134 (26.1%)99/134 (73.9%)
Most frequent serious events
Showing 10 of 36
Most frequent serious events
EventDeferiprone
Sickle cell anaemia with crisisBlood and lymphatic system disorders19/134
NeutropeniaBlood and lymphatic system disorders12/134
PyrexiaGeneral disorders5/134
CholecystectomySurgical and medical procedures3/134
AgranulocytosisBlood and lymphatic system disorders2/134
PneumoniaInfections and infestations2/134
ArthralgiaMusculoskeletal and connective tissue disorders2/134
SplenectomySurgical and medical procedures2/134
HypotensionVascular disorders2/134
ThrombocytopeniaBlood and lymphatic system disorders1/134
Most frequent other events
Showing 10 of 16
Most frequent other events
EventDeferiprone
Bone painMusculoskeletal and connective tissue disorders35/134
PyrexiaGeneral disorders33/134
Abdominal painGastrointestinal disorders26/134
Pain in extremityMusculoskeletal and connective tissue disorders18/134
Oropharyngeal painRespiratory, thoracic and mediastinal disorders18/134
Sickle cell anaemia with crisisBlood and lymphatic system disorders17/134
NasopharyngitisInfections and infestations17/134
Back painMusculoskeletal and connective tissue disorders17/134
Neutrophil count decreasedInvestigations16/134
HeadacheNervous system disorders12/134

Baseline characteristics

Age, Continuous
Age, Continuous(years)Deferiprone
Mean16.2 ± 8.6
Sex: Female, Male
Sex: Female, Male(Participants)Deferiprone
Female53
Male81
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Deferiprone
Hispanic or Latino1
Not Hispanic or Latino133
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Deferiprone
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American20
White114
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Deferiprone
Saudi Arabia5
Canada2
United States14
Egypt109
United Kingdom4
Liver iron concentration at baseline
Liver iron concentration at baseline(mg iron per gram of liver dry weight)Deferiprone
Mean14.93 ± 7.61
Cardiac iron at baseline
Cardiac iron at baseline(milliseconds)Deferiprone
Mean32.69 ± 17.66
Serum ferritin level at baseline
Serum ferritin level at baseline(micrograms per liter)Deferiprone
Mean3894 ± 2591
07

Study locations

13 sites
  • UCSF Benioff Children's Hospital Oakland
    Oakland, California 94609, United States
  • University of Michigan Comprehensive Cancer Center
    Ann Arbor, Michigan 48109, United States
  • Children's Hospital of Michigan
    Detroit, Michigan 48201, United States
  • The Children's Hospital of Philadephia
    Philadelphia, Pennsylvania 19104-4399, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Hospital for Sick Kids
    Toronto, Ontario, Canada
  • Zagazig University
    Alexandria, Egypt
  • Ain Shams University
    Cairo, Egypt
  • Cairo University
    Cairo, Egypt
  • Pediatric Hospital of Cairo University
    Cairo, Egypt
  • Asser Central Hospital
    Abha, Saudi Arabia
  • Barts and The London
    London, United Kingdom
  • Evelina Children's Hospital
    London, United Kingdom
08

References and documents

Publications

  • Elalfy MS, Hamdy M, El-Beshlawy A, Ebeid FSE, Badr M, Kanter J, Inusa B, Adly AAM, Williams S, Kilinc Y, Lee D, Fradette C, Rozova A, Temin NT, Tricta F, Kwiatkowski JL. Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years. Blood Adv. 2023 Feb 28;7(4):611-619. doi: 10.1182/bloodadvances.2021006778. PubMed 36018224 ↗

Study documents

  • Study protocol · May 1, 2017
  • Statistical analysis plan · Jun 14, 2019

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT02443545
Lead sponsor
ApoPharma
Responsible party
Sponsor
First posted
May 14, 2015
Start date
May 21, 2015
Primary completion
Apr 30, 2019
Completion
Aug 21, 2019
Results posted
Jan 10, 2024
Last update
Jan 10, 2024

Study contacts

Janet Kwiatkowski, MD
principal investigator · Children's Hospital of Philadelphia

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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