An Extension Trial to Assess the Safety of Re-dosing of Iron Isomaltoside/Ferric Derisomaltose (Monofer®/Monoferric®) (FERWON-EXT)
Primary Purpose
Iron Deficiency Anemia, Iron Deficiency Anaemia
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Iron isomaltoside/ferric derisomaltose
Sponsored by
About this trial
This is an interventional treatment trial for Iron Deficiency Anemia focused on measuring Iron Deficiency Anemia, Iron Deficiency Anaemia, IDA, Intravenous iron replacement therapy, Chronic Kidney Disease, CKD, Iron isomaltoside, Ferric derisomaltose, Monofer, Monoferric, Monover, Monofar, Monoferro
Eligibility Criteria
Inclusion Criteria:
- Completed one of the lead-in trials
- Randomised and dosed with iron isomaltoside/ferric derisomaltose in one of the lead-in trials.
- Haemoglobin (Hb) of ≤ 11 g/dL
- Screening serum ferritin (s-ferritin) ≤ 100 ng/mL, or ≤ 300 ng/mL if transferrin saturation (TSAT) ≤ 30 %
- Willingness to participate and signing the informed consent form (ICF)
Exclusion Criteria:
- Intravenous (IV) iron treatment between the lead-in trial and screening
- During 30-day period prior to screening or during the trial period; has or will be treated with a red blood cell transfusion, radiotherapy, and/or chemotherapy
- Received an investigational drug within 30 days of screening
- Decompensated liver cirrhosis or active hepatitis
- Pregnant or nursing women.
- Any other laboratory abnormality, medical condition, or psychiatric disorders which, in the opinion of the Investigator, will put the subject's disease management at risk or may result in the subject being unable to comply with the trial requirements
Sites / Locations
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site 1
- Pharmacosmos Investigational Site 2
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site
- Pharmacosmos Investigational Site 1
- Pharmacosmos Investigational Site 2
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Iron isomaltoside/ferric derisomaltose
Arm Description
Administered IV
Outcomes
Primary Outcome Measures
Number of Subjects With Adverse Drug Reactions (ADR)
Safety
Evaluate the number of subjects with adverse drug reactions (ADRs), defined as AEs that were assessed by the investigator as related or possible related to the investigational product.
Secondary Outcome Measures
Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions
Safety.
For this endpoint, the number of participants with serious or severe hypersensitivity reactions were evaluated. The hypersensitivity terms that were included in the analysis were those that started or after the first dose of treatment (i.e. treatment emergent). The terms used to define hypersensitivity were those specified by the Standardised MedDRA Queries (SMQ) for hypersensitivity, plus four additional terms: Loss of consciousness; Seizure; Syncope; Unresponsiveness.
The potential hypersensitivity AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC).
Results show only those participants that had adjudicated and confirmed serious or severe hypersensitivity reactions.
Composite Cardiovascular Adverse Events (AEs)
Safety
Results show the composite cardiovascular AEs, that started on or after the first dose of treatment (i.e. treatment emergent) up to month 6.
The reported potential cardiovascular AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC).
The potential cardiovascular AEs included the following:
Death due to any cause
Non-fatal myocardial infarction
Non-fatal stroke
Unstable angina requiring hospitalisation
Congestive heart failure requiring hospitalisation or medical intervention
Arrhythmias
Hypertension
Hypotension
Results show only those participants that had adjudicated and confirmed treatment-emergent composite cardiovascular AEs.
Time to First Composite Cardiovascular Safety AE
Safety
Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit. Only the adjudicated and confirmed composite cardiovascular safety AEs, as judged by the Clinical Endpoint Adjudication Committee (CEAC), were considered for this endpoint.
Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit.
S-phosphate <2 mg/dL at Any Time From Baseline to Week 26
Safety
Results show the number of trial participants and their status of s-phosphate <2 mg/dL, at any time from baseline to week 26.
Change in Hb From Baseline to Week 2, 13, and 26
Efficacy.
Change in Hb from baseline to week 2, 13, and 26.
Change in S-ferritin From Baseline to Week 2, 13, and 26
Efficacy.
Change in s-ferritin from baseline to week 2, 13, and 26.
Change in Transferrin Saturation (TSAT) From Baseline to Week 2, 13, and 26
Efficacy
Change in transferrin saturation (TSAT) from baseline to week 2, 13, and 26.
TSAT is the value of serum iron divided by the total iron-binding capacity and the unit is %, which referrers to % of iron-binding sites of transferrin being occupied by iron.
Change in S-iron From Baseline to Week 2, 13, and 26
Efficacy.
Change in s-iron from baseline to week 2, 13, and 26.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02962648
Brief Title
An Extension Trial to Assess the Safety of Re-dosing of Iron Isomaltoside/Ferric Derisomaltose (Monofer®/Monoferric®)
Acronym
FERWON-EXT
Official Title
An Open-label, Multicentre, Extension Trial to Assess the Safety of Re-dosing of Intravenous Iron Isomaltoside/Ferric Derisomaltose (Monofer®/Monoferric®)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
January 9, 2017 (Actual)
Primary Completion Date
June 12, 2018 (Actual)
Study Completion Date
June 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacosmos A/S
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Evaluate safety and efficacy of intravenous (IV) iron isomaltoside/ferric derisomaltose re-dosing, in subjects who were previously treated with iron isomaltoside/ferric derisomaltose.
Detailed Description
Among the various formulations of parenteral iron that are currently available, iron isomaltoside/ferric derisomaltose may allow flexibility in terms of high and rapid dosing. Up to now, most clinical trials with intravenous (IV) iron treatment were of 4-12 weeks in duration; longer trials are warranted to follow-up on long-term safety.
The aim of the trial was to evaluate the safety and efficacy of IV iron isomaltoside/ferric derisomaltose re-dosing in subjects who were previously treated with iron isomaltoside/ferric derisomaltose in lead-in trials.
This was a 6-months extension trial lasting 26 weeks. Eligible subjects attended 5 visits: screening, baseline (subjects treated with a single IV dose of 1000 mg iron isomaltoside/ferric derisomaltose), and follow-up visits at week 2, 13, and 26 weeks after the IV dose, for safety and efficacy assessments.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron Deficiency Anemia, Iron Deficiency Anaemia
Keywords
Iron Deficiency Anemia, Iron Deficiency Anaemia, IDA, Intravenous iron replacement therapy, Chronic Kidney Disease, CKD, Iron isomaltoside, Ferric derisomaltose, Monofer, Monoferric, Monover, Monofar, Monoferro
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
103 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Iron isomaltoside/ferric derisomaltose
Arm Type
Experimental
Arm Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Iron isomaltoside/ferric derisomaltose
Other Intervention Name(s)
Monofer®, Monoferric®, Monover®, Monofar®, Monoferro®
Intervention Description
Iron isomaltoside/ferric derisomaltose (Monofer®/Monoferric®; 100 mg/mL) was the test product in this trial.
The dose of iron isomaltoside/ferric derisomaltose for the individual subject was set to 1000 mg. The dose was diluted in 100 mL 0.9 % sodium chloride from the site's supply and administered over approximately 20 minutes using IV infusion.
Primary Outcome Measure Information:
Title
Number of Subjects With Adverse Drug Reactions (ADR)
Description
Safety
Evaluate the number of subjects with adverse drug reactions (ADRs), defined as AEs that were assessed by the investigator as related or possible related to the investigational product.
Time Frame
Baseline to week 26
Secondary Outcome Measure Information:
Title
Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions
Description
Safety.
For this endpoint, the number of participants with serious or severe hypersensitivity reactions were evaluated. The hypersensitivity terms that were included in the analysis were those that started or after the first dose of treatment (i.e. treatment emergent). The terms used to define hypersensitivity were those specified by the Standardised MedDRA Queries (SMQ) for hypersensitivity, plus four additional terms: Loss of consciousness; Seizure; Syncope; Unresponsiveness.
The potential hypersensitivity AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC).
Results show only those participants that had adjudicated and confirmed serious or severe hypersensitivity reactions.
Time Frame
Baseline to week 26
Title
Composite Cardiovascular Adverse Events (AEs)
Description
Safety
Results show the composite cardiovascular AEs, that started on or after the first dose of treatment (i.e. treatment emergent) up to month 6.
The reported potential cardiovascular AEs were adjudicated in a blinded fashion by an independent Clinical Endpoint Adjudication Committee (CEAC).
The potential cardiovascular AEs included the following:
Death due to any cause
Non-fatal myocardial infarction
Non-fatal stroke
Unstable angina requiring hospitalisation
Congestive heart failure requiring hospitalisation or medical intervention
Arrhythmias
Hypertension
Hypotension
Results show only those participants that had adjudicated and confirmed treatment-emergent composite cardiovascular AEs.
Time Frame
Baseline to week 26
Title
Time to First Composite Cardiovascular Safety AE
Description
Safety
Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit. Only the adjudicated and confirmed composite cardiovascular safety AEs, as judged by the Clinical Endpoint Adjudication Committee (CEAC), were considered for this endpoint.
Time to first composite cardiovascular AE was defined as the actual time in days from first dose of treatment until the date of the composite cardiovascular AE. For subjects not reporting a composite cardiovascular AE, the time was censored at the date of the last attended visit.
Time Frame
Baseline, week 2, 13, and 26
Title
S-phosphate <2 mg/dL at Any Time From Baseline to Week 26
Description
Safety
Results show the number of trial participants and their status of s-phosphate <2 mg/dL, at any time from baseline to week 26.
Time Frame
Baseline to week 26
Title
Change in Hb From Baseline to Week 2, 13, and 26
Description
Efficacy.
Change in Hb from baseline to week 2, 13, and 26.
Time Frame
Baseline, week 2, 13, and 26
Title
Change in S-ferritin From Baseline to Week 2, 13, and 26
Description
Efficacy.
Change in s-ferritin from baseline to week 2, 13, and 26.
Time Frame
Baseline, week 2, 13, and 26
Title
Change in Transferrin Saturation (TSAT) From Baseline to Week 2, 13, and 26
Description
Efficacy
Change in transferrin saturation (TSAT) from baseline to week 2, 13, and 26.
TSAT is the value of serum iron divided by the total iron-binding capacity and the unit is %, which referrers to % of iron-binding sites of transferrin being occupied by iron.
Time Frame
Baseline, week 2, 13, and 26
Title
Change in S-iron From Baseline to Week 2, 13, and 26
Description
Efficacy.
Change in s-iron from baseline to week 2, 13, and 26.
Time Frame
Baseline, week 2, 13, and 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Completed one of the lead-in trials
Randomised and dosed with iron isomaltoside/ferric derisomaltose in one of the lead-in trials.
Haemoglobin (Hb) of ≤ 11 g/dL
Screening serum ferritin (s-ferritin) ≤ 100 ng/mL, or ≤ 300 ng/mL if transferrin saturation (TSAT) ≤ 30 %
Willingness to participate and signing the informed consent form (ICF)
Exclusion Criteria:
Intravenous (IV) iron treatment between the lead-in trial and screening
During 30-day period prior to screening or during the trial period; has or will be treated with a red blood cell transfusion, radiotherapy, and/or chemotherapy
Received an investigational drug within 30 days of screening
Decompensated liver cirrhosis or active hepatitis
Pregnant or nursing women.
Any other laboratory abnormality, medical condition, or psychiatric disorders which, in the opinion of the Investigator, will put the subject's disease management at risk or may result in the subject being unable to comply with the trial requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pharmacosmos A/S Clinical and Non-clinical Research
Organizational Affiliation
Pharmacosmos A/S
Official's Role
Study Director
Facility Information:
Facility Name
Pharmacosmos Investigational Site
City
Chula Vista
State/Province
California
ZIP/Postal Code
91910
Country
United States
Facility Name
Pharmacosmos Investigational Site 1
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
Pharmacosmos Investigational Site 2
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Porterville
State/Province
California
ZIP/Postal Code
93257
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Doral
State/Province
Florida
ZIP/Postal Code
33172
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33147
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33409
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70125
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71101
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Plainsboro
State/Province
New Jersey
ZIP/Postal Code
08536
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87109
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Pharmacosmos Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Pharmacosmos Investigational Site 1
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Pharmacosmos Investigational Site 2
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
An Extension Trial to Assess the Safety of Re-dosing of Iron Isomaltoside/Ferric Derisomaltose (Monofer®/Monoferric®)
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