Restless Legs Syndrome (RLS)Phase 2NCT02826681
Randomized, Placebo-controlled Trial of Ferric Carboxymaltose in RLS Patients With Iron-deficiency Anemia
A Phase 2 study testing Injectafer® (Ferric Carboxymaltose - FCM) in people with Restless Legs Syndrome (RLS), run by American Regent, Inc. at 8 sites in United States.
Trial summary
Treatment Phase I and II Primary Objective: To evaluate the efficacy and safety of FCM (750 mg dose x 2) for treatment of Restless Legs Syndrome (RLS) in patients with iron-deficiency anemia (IDA). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Restless Legs Syndrome (RLS)
- What is being tested?
- Injectafer® (Ferric Carboxymaltose - FCM)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 8 sitesUnited States
- Study dates
- 10 Jul 2017to 1 Jul 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subject ≥18 years of age who is able to give informed consent.
- Confirmed diagnosis of RLS based on the Cambridge-Hopkins Diagnostic Questionnaire (CHDQ) and the Hopkins-Hening Telephone Diagnostic Interview (HDTI).
- IRLSS score ≥15 plus RLS symptoms for at least 3 months and currently occurring ≥2 nights per week.
- Iron-deficiency anemia defined as an Hgb <12 g/dl with a ferritin <20 ng/mL, or ferritin <100 when TSAT is <18%.
- Subjects on sleep medication must be on a stable dose for at least 6 months prior screening.
- Subjects at risk for pregnancy must have a negative pregnancy test at screening and be practicing an acceptable form of birth control, have had a hysterectomy or tubal ligation, or otherwise be incapable of pregnancy, or have practiced any of the following methods of contraception for at least one month prior to study entry: hormonal contraceptives, spermicide with barrier, intrauterine device, or partner sterility.
Who cannot join
- Disorders that require treatment with the same medications used for RLS include:
- peripheral neuropathy and neurodegenerative disorders (i.e. Parkinson's disease or dementia).
- Current (past 4 weeks) use of drugs that may cause or treat RLS, e.g. opioids, calcium channel alpha-2-delta ligands, anti-depressants, dopaminergic agonist or antagonists, or centrally-acting antihistamines.
- Any medical conditions contraindicated to MRI.
- Abnormal MRI at baseline that would confound the outcome measures.
- Secondary RLS due to neurological conditions or head trauma.
Show all 22Show fewer
- History of hemochromatosis, hemosiderosis, other iron storage disorders or iron metabolism disorders.
- Women with clinically significant uterine bleeding (>200 cc blood loss) during the six months prior to screening.
- Liver transaminases (AST or ALT) greater than two times the upper limit of normal (ULN).
- Known positive Hepatitis B antigen (HBs Ag), unless positive test can be attributed to receipt of Hepatitis B vaccination in childhood or Hepatitis C viral antibody (HCV) with evidence of active hepatitis (i.e., AST/ALT greater than two times the ULN).
- Known positive HIV-1 or HIV-2 antibodies (anti-HIV).
- Active acute or known chronic infections.
- Rheumatoid arthritis with symptoms or signs of active inflammation.
- Pregnant and lactating women.
- Known hypersensitivity reaction to any component of Injectafer® (ferric carboxymaltose).
- Previously randomized to Injectafer® (FCM or VIT-45) in a clinical trial.
- Previous IV iron treatment for RLS.
- Parenteral iron, erythropoiesis stimulating agent use or blood transfusion within six weeks prior to the screening visit.
- Planned elective surgery during the study year.
- Chronic alcohol or drug abuse within the past six months.
- Any other pre-existing laboratory abnormality, medical condition, or disease that, in the opinion of Investigator, may cause the subject to be unsuitable for the study or place the subject at potential risk from being in the study, e.g. a malignancy, uncontrolled hypertension, unstable ischemic heart disease, or uncontrolled diabetes mellitus.
- Subject is unwilling or has conditions that would prohibit them from complying with the study requirements.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224-2780
Alliance for Multispeciality Research
Fort Myers, Florida, 33912
Clinical Trial Network
Houston, Texas, 77074
Neurology Center of Las Vegas
Las Vegas, Nevada, 89128
Synergy San Diego
Lemon Grove, California, 91945
CNS Healthcare
Orlando, Florida, 32801
The Polyclinic
Seattle, Washington, 98104
Boston Neuro Research
South Dartmouth, Massachusetts, 02169
About this study
Official title: Randomized, Placebo-controlled Trial of Ferric Carboxymaltose in Restless Legs Syndrome Patients With Iron-deficiency Anemia
Treatment Phase I and II Primary Objective: To evaluate the efficacy and safety of FCM (750 mg dose x 2) for treatment of Restless Legs Syndrome (RLS) in patients with iron-deficiency anemia (IDA).
Long-Term Extension Phase III Primary Objective: To evaluate the duration of effect of prior FCM treatment and to determine the effectiveness of further iron repletion with FCM when RLS symptoms worsen or reoccur.
Read the detailed description
This will be a Phase II, randomized, placebo-controlled study. All subjects who meet the inclusion criteria, with no exclusion criteria, will qualify to enter the Screening Phase. The study will enroll 70 eligible subjects to receive blinded study drug in Treatment Phase I. All eligible subjects will be randomized in a 1:1 ratio to receive a blinded dose of either FCM 750 mg undiluted slow intravenous (IV) push at 100 mg/minute or a Placebo (15 ml of Normal Saline [NS]) IV push at 2 ml/minute on Day 0 and 7.
A subject will be defined at Day 42 as a Responder if the International Restless Legs Syndrome Severity Scale (IRLSS) score is ≤10 or if the IRLSS score is >10 with a Clinical Global Impression-Improvement (CGI-I) score of much or very much improvement and the subject does not request further treatment for RLS. A subject will be defined as a treatment Non-Responder if neither of these criteria are met.
Non-Responders who do not meet the laboratory criteria for additional dosing will be discontinued from the study and treated for RLS as deemed appropriate by the referring physician. Subjects who are Non-Responders at the end of Treatment Phase I and met the necessary laboratory criteria (ferritin <300 ng/mL and a TSAT <45%) will consented for enrollment in Treatment Phase II of the study. These subjects will receive the first of two unblinded doses of FCM (undiluted slow IV push 750 mg 100 mg/minute) on Day 0 of Phase II, which will occur within 7 days of the completing Treatment Phase I visit. The subjects will then receive the second dose of FCM (undiluted slow IV push 750 mg 100 mg/minute) on Day 7. All treated subjects will have blood samples taken for hematology, chemistries and iron indices on Day 14. Treatment efficacy (IRLSS score), medication review and adverse events assessment by phone will be done on Day 28. All subjects will return to the clinic on Day 42 for end of study assessments. Subjects completing Treatment Phase II will be re-evaluated on Day 42 and defined as either a Responder or Non-Responder, using the same criteria described above. Subjects deemed as treatment Non-Responders will be discontinued from the study after final assessments are complete.
Subjects who are evaluated on Day 42 (Week 6) as Responders from either Treatment Phase I or Treatment Phase II will continue through into the 46-Week, Long-Term Extension Phase III of the study, and be monitored and assessed by phone for RLS symptoms (IRLSS and Hopkins RLS-Sleep Quality Questionnaire [HRSQ]) and adverse events on (approximately every 9 weeks) Weeks 15, 25, 34, 43 and 52 (final follow-up visit). During Phase III subjects may receive additional unblinded treatments with FCM if at any time the subject reports worsening of RLS symptoms (an increase >4 points on the IRLSS compared to the last evaluation captured for that subject) and laboratory criteria are met (ferritin <300 ng/mL and a TSAT <45%). Subjects will receive a single FCM 750 mg undiluted slow IV push at 100 mg/minute. See section 6.6 for dosing and assessment outline. No additional treatment will be allowed after the Week 46. A final face-to-face study visit will occur on Week 52 (approximately 365 days since initial Day 0 Treatment). If a clinic visit is not possible, final evaluation will be completed by phone.
- Conditions
- Restless Legs Syndrome (RLS)
- Being tested
- Injectafer® (Ferric Carboxymaltose - FCM), Placebo (Normal Saline)
- Medical subject headings
- Restless Legs Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injectafer® (Ferric Carboxymaltose - FCM)Drug
Also called Ferinject®, Iroprem®, Renegy®
Intravenous Iron
Placebo (Normal Saline)Drug
Also called Normal Saline
Normal Saline Solution
| Study group | Role | What they receive |
|---|---|---|
| Injectafer | Active comparator | 750 mg undiluted slow IVpush (100 mg/minute) of Injectafer® (Ferric Carboxymaltose - FCM) Receives: Drug: Injectafer® (Ferric Carboxymaltose - FCM) |
| Normal Saline | Placebo comparator | Placebo (15 ml of Normal Saline [NS]) IV push at 2 ml/minute on Day 0 and 7. Receives: Drug: Placebo (Normal Saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Phase I: IRLSS Score Change
IRLSS (International Restless Legs Syndrome Severity Scale) score change from baseline to Day 42 with comparison between FCM (Ferric Carboxymaltose) vs. Placebo.
Measured: Baseline to Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2016 (estimated)
- Study start10 Jul 2017
- Primary completion4 Sep 2021
- Study completion1 Jul 2022
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Restless Legs Syndrome (RLS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- American Regent, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Khaled Khechen, MD, Study director, American Regent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02826681
- Sponsor's protocol ID
- 1VIT15042
- Status last verified
- Aug 2022
- First submitted
- 30 Jun 2016
- Last updated
- 11 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Placebo-controlled Trial of Ferric Carboxymaltose in Restless Legs Syndrome Patients With Iron-deficiency Anemia
- ClinicalTrials.gov ID
- NCT02826681
- Acronym / sponsor ID
- 1VIT15042
- Conditions
- Restless Legs Syndrome (RLS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 70 participants (actual)
- Lead sponsor
- American Regent, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Jul 2017 (actual)
- Primary completion
- 4 Sep 2021 (actual)
- Study completion
- 1 Jul 2022 (actual)
- First posted
- 11 Jul 2016 (estimated)
- Results
- Posted 14 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment Phase I and II Primary Objective: To evaluate the efficacy and safety of FCM (750 mg dose x 2) for treatment of Restless Legs Syndrome (RLS) in patients with iron-deficiency anemia (IDA).
Long-Term Extension Phase III Primary Objective: To evaluate the duration of effect of prior FCM treatment and to determine the effectiveness of further iron repletion with FCM when RLS symptoms worsen or reoccur.
Detailed description
This will be a Phase II, randomized, placebo-controlled study. All subjects who meet the inclusion criteria, with no exclusion criteria, will qualify to enter the Screening Phase. The study will enroll 70 eligible subjects to receive blinded study drug in Treatment Phase I. All eligible subjects will be randomized in a 1:1 ratio to receive a blinded dose of either FCM 750 mg undiluted slow intravenous (IV) push at 100 mg/minute or a Placebo (15 ml of Normal Saline [NS]) IV push at 2 ml/minute on Day 0 and 7.
A subject will be defined at Day 42 as a Responder if the International Restless Legs Syndrome Severity Scale (IRLSS) score is ≤10 or if the IRLSS score is >10 with a Clinical Global Impression-Improvement (CGI-I) score of much or very much improvement and the subject does not request further treatment for RLS. A subject will be defined as a treatment Non-Responder if neither of these criteria are met.
Non-Responders who do not meet the laboratory criteria for additional dosing will be discontinued from the study and treated for RLS as deemed appropriate by the referring physician. Subjects who are Non-Responders at the end of Treatment Phase I and met the necessary laboratory criteria (ferritin <300 ng/mL and a TSAT <45%) will consented for enrollment in Treatment Phase II of the study. These subjects will receive the first of two unblinded doses of FCM (undiluted slow IV push 750 mg 100 mg/minute) on Day 0 of Phase II, which will occur within 7 days of the completing Treatment Phase I visit. The subjects will then receive the second dose of FCM (undiluted slow IV push 750 mg 100 mg/minute) on Day 7. All treated subjects will have blood samples taken for hematology, chemistries and iron indices on Day 14. Treatment efficacy (IRLSS score), medication review and adverse events assessment by phone will be done on Day 28. All subjects will return to the clinic on Day 42 for end of study assessments. Subjects completing Treatment Phase II will be re-evaluated on Day 42 and defined as either a Responder or Non-Responder, using the same criteria described above. Subjects deemed as treatment Non-Responders will be discontinued from the study after final assessments are complete.
Subjects who are evaluated on Day 42 (Week 6) as Responders from either Treatment Phase I or Treatment Phase II will continue through into the 46-Week, Long-Term Extension Phase III of the study, and be monitored and assessed by phone for RLS symptoms (IRLSS and Hopkins RLS-Sleep Quality Questionnaire [HRSQ]) and adverse events on (approximately every 9 weeks) Weeks 15, 25, 34, 43 and 52 (final follow-up visit). During Phase III subjects may receive additional unblinded treatments with FCM if at any time the subject reports worsening of RLS symptoms (an increase >4 points on the IRLSS compared to the last evaluation captured for that subject) and laboratory criteria are met (ferritin <300 ng/mL and a TSAT <45%). Subjects will receive a single FCM 750 mg undiluted slow IV push at 100 mg/minute. See section 6.6 for dosing and assessment outline. No additional treatment will be allowed after the Week 46. A final face-to-face study visit will occur on Week 52 (approximately 365 days since initial Day 0 Treatment). If a clinic visit is not possible, final evaluation will be completed by phone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Injectafer | Active comparator | Drug: Injectafer® (Ferric Carboxymaltose - FCM)750 mg undiluted slow IVpush (100 mg/minute) of Injectafer® (Ferric Carboxymaltose - FCM) |
| Normal Saline | Placebo comparator | Drug: Placebo (Normal Saline)Placebo (15 ml of Normal Saline [NS]) IV push at 2 ml/minute on Day 0 and 7. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female subject ≥18 years of age who is able to give informed consent.
- Confirmed diagnosis of RLS based on the Cambridge-Hopkins Diagnostic Questionnaire (CHDQ) and the Hopkins-Hening Telephone Diagnostic Interview (HDTI).
- IRLSS score ≥15 plus RLS symptoms for at least 3 months and currently occurring ≥2 nights per week.
- Iron-deficiency anemia defined as an Hgb <12 g/dl with a ferritin <20 ng/mL, or ferritin <100 when TSAT is <18%.
- Subjects on sleep medication must be on a stable dose for at least 6 months prior screening.
Key exclusion criteria (22 listed)
- Disorders that require treatment with the same medications used for RLS include:
- peripheral neuropathy and neurodegenerative disorders (i.e. Parkinson's disease or dementia).
- Current (past 4 weeks) use of drugs that may cause or treat RLS, e.g. opioids, calcium channel alpha-2-delta ligands, anti-depressants, dopaminergic agonist or antagonists, or centrally-acting antihistamines.
- Any medical conditions contraindicated to MRI.
- Abnormal MRI at baseline that would confound the outcome measures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Injectafer® (Ferric Carboxymaltose - FCM)Also: Ferinject®, Iroprem®, Renegy®Intravenous Iron | Drug | Injectafer |
| Placebo (Normal Saline)Also: Normal SalineNormal Saline Solution | Drug | Normal Saline |
Primary outcome
Treatment Phase I: IRLSS Score Change
Time frame: Baseline to Day 42
IRLSS (International Restless Legs Syndrome Severity Scale) score change from baseline to Day 42 with comparison between FCM (Ferric Carboxymaltose) vs. Placebo.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Restless Legs Syndrome (RLS)
RecruitingObservational study
Lemborexant vs Clonidine vs Sedatives to Treat Insomnia in Chronic Pain Patients
Chronic Insomnia, Chronic Pain
Not yet recruiting
Neuromodulation to Overcome Severe Restless Legs Syndrome
Restless Leg Syndrome (RLS), Spinal Cord Stimulation (SCS)
Not yet recruitingPhase 2
Tolerability and Efficacy of CBD Extract for RLS Treatment
Restless Leg Syndrome
Recruiting
Functional Connectivity of the Interoceptive Network in RLS
Restless Legs Syndrome
Not yet recruitingPhase 2
Intravenous Iron in the Management of Drug-resistant Restless Legs syndromeI
Restless Legs Syndrome (RLS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Khaled Khechen, MD study director
American Regent
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Injectafer® (Ferric Carboxymaltose - FCM) in people with Restless Legs Syndrome (RLS), run by American Regent, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Phase I: IRLSS Score Change (time frame: Baseline to Day 42). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.