Restless Legs Syndrome (RLS)Phase 3NCT02397057
Placebo-Controlled Study to Investigate the Efficacy & Safety of Injectafer in the Treatment of RLS
A Phase 3 study testing Injectafer in people with Restless Legs Syndrome (RLS), run by American Regent, Inc. at 19 sites in United States.
Trial summary
This will be a Phase III, double blinded, multi-center, randomized, placebo-controlled study. Eligible subjects will be randomized in a 1:1 ratio to receive Injectafer or Placebo on days 0 and 5. All treated subjects will be followed for efficacy and safety for 12 months. 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
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 209 participants
- Where
- 19 sitesUnited States
- Study dates
- Jan 2015to Jan 2018
- Phase
- Phase 3
- 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's ≥18 years of age, willing and able to give informed consent to the study.
- RLS symptoms affirming diagnosis. The IRLS Diagnostic Criteria must be met:
- An urge (distressing need) to move the legs usually associated with painful or uncomfortable sensations in the legs. The urge to move may be present without the uncomfortable sensations. The arms or other body parts may be involved in addition to the legs.
- The urge to move or unpleasant sensations are worse or exclusively present at rest or inactivity, such as lying down or sitting.
- The urge to move or unpleasant sensations are partially/temporarily relieved with walking or moving the legs.
- The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night. When symptoms are severe, the worsening at night may not be noticeable but must have been previously present.
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- Subjects should be on monotherapy for RLS. Treatment should be stable for at least 8 weeks prior to screening (See approved RLS Therapies/Regimen in Appendix III).
- A score ≥15 on the IRLS Rating Scale at screening and on Day 0 prior to dosing.
- Subjects on anti-depressants and sleep medications must be on a stable dose for at least 6 months.
- Subject has regular sleep hours between 9 pm and 9 am.
- Subjects at risk for pregnancy must have a negative pregnancy test at baseline 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
- RLS 2° to other disease or injury.
- Disorders that require treatment with the same medications used for RLS include: peripheral neuropathy and neurodegenerative disorders (i.e. Parkinson's Disease or Dementia).
- Stage 4 - 5 CKD, subjects on dialysis or anticipated to start dialysis while participating in this study.
- Any pain related (e.g., frequent muscle cramps, myalgia, fibromyalgia) or sleep related disorders (e.g. sleep apnea, unless on stable Continuous Positive Airway Pressure [CPAP]) which may confound the outcome measures.
- Subjects with multiple sclerosis.
- History of neuroleptic akathisia.
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- Parenteral iron use within 6 weeks prior to screening.
- History of >10 blood transfusions in the past 2 years.
- Anticipated need for blood transfusion during the study.
- Known hypersensitivity reaction to any component of Injectafer® (Ferric Carboxymaltose).
- Previously randomized to Injectafer® (FCM or VIT-45) in a clinical trial.
- Current, active or acute or chronic infection other than viral upper respiratory tract infection
- Malignancy (other than basal or squamous cell skin cancer or the subject has been cancer free for ≥ 5 years).
- Pregnant or lactating women.
- Seizure disorder currently being treated with medication.
- Baseline ferritin ≥300 ng/mL.
- Baseline TSAT ≥45%.
- History of hemochromatosis, hemosiderosis, or other iron storage disorders.
- AST or ALT greater than 2 times the upper limit of normal (ULN).
- Hemoglobin greater than the ULN.
- Known positive hepatitis B antigen (HBsAg), 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 the upper limit of normal).
- Known positive HIV-1/HIV-2 antibodies (anti-HIV).
- Received an investigational drug within 30 days before randomization.
- Chronic alcohol or drug abuse within the past 6 months.
- Any other pre-existing laboratory abnormality, medical condition or disease, which per the investigator may put the subject at risk if they participate in the study.
- Subject unable or unwilling to comply with the study requirements.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
Neuromedical Clinical of Central Louisiana
Alexandria, Louisiana, 71301
Neurology Offices of South FL
Boca Raton, Florida, 33428
Massachusetts General Hospital, Sleep Disorders Clinical Research Program
Boston, Massachusetts, 02114
Ctr for Brain & Neuro Care, LLC
Fulton, Maryland, 20759
Guilford Neurologic Associates
Greensboro, North Carolina, 27405
Egret Bay Neurology
Houston, Texas, 77058
Tri-State Mountain Neurology Associates
Johnson City, Tennessee, 37604
Desert Neurology
Las Vegas, Nevada, 89119
Neurology Center of Las Vegas
Las Vegas, Nevada, 89128
MidAmmerica Neuroscience Institute
Lenexa, Kansas, 66214-1505
Central Kentucky Research Assoc., Inc.
Lexington, Kentucky, 40509
Elite Research Institute
Miami, Florida, 33169
Coastal Clinical Research, Inc.
Mobile, Alabama, 36608
Synergy San Diego
National City, California, 91950
Metrolina Neurological Associates
Old Point Station, South Carolina, 29707
Desert Valley Research
Rancho Mirage, California, 92270
Anderson Clinical Research
Redlands, California, 92374
The Polyclinic, Madison Center
Seattle, Washington, 98104
Saad Upstate Neurology
Spartanburg, South Carolina, 29307
About this study
Official title: A Double-Blinded, Multi-Center, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Injectafer (Ferric Carboxymaltose) in the Treatment of Restless Legs Syndrome (RLS)
This will be a Phase III, double blinded, multi-center, randomized, placebo-controlled study. Eligible subjects will be randomized in a 1:1 ratio to receive Injectafer or Placebo on days 0 and 5. All treated subjects will be followed for efficacy and safety for 12 months. The subject's participation in the study will be for approximately 1 year from Day 0.
Read the detailed description
This will be a Phase III, double blinded, multi-center, randomized, placebo-controlled study. Eligible subjects will be randomized in a 1:1 ratio to receive Injectafer or Placebo on days 0 and 5. All treated subjects will be followed for efficacy and safety for 12 months. Subjects will visit the clinic on Days 0 and 5 for treatment, and then on Days 14, 42, 168, and 365. In between the clinic visits subjects will be contacted remotely on Days 84, 126, 210, 252, 294, and 336. The subject's participation in the study will be for approximately 1 year from Day 0.
- Conditions
- Restless Legs Syndrome (RLS)
- Being tested
- Injectafer, Placebo
- 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.
InjectaferDrug
Also called Ferinject®, Iroprem®, Renegy®
PlaceboOther
Also called Normal Saline
| Study group | Role | What they receive |
|---|---|---|
| Injectafer | Active comparator | Two doses of Injectafer 750 mg undiluted dose at 100 mg/minute given 5 days apart for a total of 1500 mgs. Receives: Drug: Injectafer |
| Normal Saline | Placebo comparator | IV Placebo (15ml of Normal Saline) IV push at 2ml/minute Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
International Restless Legs Syndrome (IRLS) Total Score Change From Baseline on Day 42
Summary of the actual values of IRLS total score on baseline and Day 42, and the change from baseline to Day 42.
Eligible subjects were to have met the following requirements prior to receiving additional treatment:
A baseline score ≥ 15 on the International Restless Legs Syndrome (IRLS) Rating Scale. The minimum score is 15 with the maximum of 40. A score of less than 15 is not an indicator of RLS. However, a score of 15 or greater is an indicator of RLS. Further increase indicates more severe disease.
Measured: Baseline and Day 42
Proportion of Patients Rated as Much or Very Much Improved With the Clinical Global Impression (CGI) Performed by Investigator (CGI-I)
Responder is defined as subjects rated as much or very much improved with the CGI-I on Day 42. Summary of the number (percentage) of CGI-I responder. Per the protocol, the he CGI is a 3-item observer-rated scale that measures illness severity (CGIS), global improvement or change (CGIC) and therapeutic response. The scale requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.
Measured: Day 42
Secondary outcomes (5)
Clinical Global Impression-Improvement (CGI-S) by Subject
Similar to the CGI-I except this is self-reported, 7-item scale for assessment of symptoms after treatment with the rating as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Measured: Day 42
Restless Legs Syndrome Quality of Life (RLS-QLI) Change From Baseline to Day 42.
The Restless Legs Syndrome Quality of Life (RLS-QLI) instrument, a self-assessment, 17-item questionnaire with four scales identified through factor analysis: Daily Function, Social Function, Sleep Quality, and Emotional Well-Being, developed to facilitate clinical research on RLS. Scoring Instructions below:
- Social Function = Sum (Items 1, 2, 3, 4), subtract 4, divide by 16, multiply by 100
- Daily Function = Sum (Items 5, 6, 13,14, 15, 16), subtract 6, divide by 24, multiply by 100
- Sleep Quality = Sum (Item 7, 8, 9, 17), subtract 4, divide by 18, multiply by 100
- Emotional Well-being = Sum (Items 10, 11, 12), subtract 3, divide by 12, multiply by 100
Note: Resulting scores range between 0-100.
Higher scores on the RLS-QLI indicate a lower quality of life. Lower scores indicate a higher quality of life.
Measured: Baseline and Day 42
Fatigue Linear Analog Scale Change From Baseline
The Fatigue Linear Analog Scale is a self-assessment scale in which a 100 mm line is used to measure the severity of fatigue and its effect on a person's activities and lifestyle. The scale severity measure ranges from No Fatigue to Worst Possible Fatigue.
Measured: Baseline and Day 42
Medical Outcomes Study(MOS) Sleep Scale Change From Baseline to Day 42
The MOS-Sleep scale, is a 12-item standardized, validated questionnaire for assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache which has been demonstrated to be sensitive to RLS treatment effects. This questionnaire provides information about sleep quality. Individual questions can be used for analysis but summary or index scores of a group of questions, is more commonly used in analysis.
The "quantity of sleep" dimension is the average number of hours of sleep per night reported by the patient and the "optimal sleep" is a dichotomized version that is "yes" when the number of hours of sleep is 7 or 8. The scores of the dimensions and of the sleep problem index were converted to a 0 to 100 scale, with higher scores reflecting more of the attribute implied by the name (e.g. greater sleep disturbance, greater adequacy of sleep).
Measured: Change from Baseline and Day 42.
Time Off Pre-Enrollment Prescribed Restless Legs Syndrome (RLS) Medications
Subjects could start tapering off pre-enrollment prescribed RLS medications after Day 5 until Day 365.
Measured: Time from Day 5 to Day 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2015 (estimated)
- Study startJan 2015
- Primary completionJan 2018
- Study completionJan 2018
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 209 participants (actual)
Sponsor and investigators
- Lead sponsor
- American Regent, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark Falone, MD, Study director, American Regent, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02397057
- Sponsor's protocol ID
- 1VIT14037
- Status last verified
- Oct 2021
- First submitted
- 18 Mar 2015
- Last updated
- 12 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Earley CJ, Garcia-Borreguero D, Falone M, Winkelman JW. Clinical efficacy and safety of intravenous ferric carboxymaltose for treatment of restless legs syndrome: a multicenter, randomized, placebo-controlled clinical trial. Sleep. 2024 Jul 11;47(7):zsae095. doi: 10.1093/sleep/zsae095.
PubMed 38625730
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blinded, Multi-Center, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Injectafer (Ferric Carboxymaltose) in the Treatment of Restless Legs Syndrome (RLS)
- ClinicalTrials.gov ID
- NCT02397057
- Acronym / sponsor ID
- 1VIT14037
- Conditions
- Restless Legs Syndrome (RLS)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 209 participants (actual)
- Lead sponsor
- American Regent, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2015 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 24 Mar 2015 (estimated)
- Results
- Posted 12 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a Phase III, double blinded, multi-center, randomized, placebo-controlled study. Eligible subjects will be randomized in a 1:1 ratio to receive Injectafer or Placebo on days 0 and 5. All treated subjects will be followed for efficacy and safety for 12 months. The subject's participation in the study will be for approximately 1 year from Day 0.
Detailed description
This will be a Phase III, double blinded, multi-center, randomized, placebo-controlled study. Eligible subjects will be randomized in a 1:1 ratio to receive Injectafer or Placebo on days 0 and 5. All treated subjects will be followed for efficacy and safety for 12 months. Subjects will visit the clinic on Days 0 and 5 for treatment, and then on Days 14, 42, 168, and 365. In between the clinic visits subjects will be contacted remotely on Days 84, 126, 210, 252, 294, and 336. The subject's participation in the study will be for approximately 1 year from Day 0.
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: InjectaferTwo doses of Injectafer 750 mg undiluted dose at 100 mg/minute given 5 days apart for a total of 1500 mgs. |
| Normal Saline | Placebo comparator | Other: PlaceboIV Placebo (15ml of Normal Saline) IV push at 2ml/minute |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female subject's ≥18 years of age, willing and able to give informed consent to the study.
- RLS symptoms affirming diagnosis. The IRLS Diagnostic Criteria must be met:
- Subjects should be on monotherapy for RLS. Treatment should be stable for at least 8 weeks prior to screening (See approved RLS Therapies/Regimen in Appendix III).
- A score ≥15 on the IRLS Rating Scale at screening and on Day 0 prior to dosing.
- Subjects on anti-depressants and sleep medications must be on a stable dose for at least 6 months.
Key exclusion criteria (26 listed)
- RLS 2° to other disease or injury.
- Disorders that require treatment with the same medications used for RLS include: peripheral neuropathy and neurodegenerative disorders (i.e. Parkinson's Disease or Dementia).
- Stage 4 - 5 CKD, subjects on dialysis or anticipated to start dialysis while participating in this study.
- Any pain related (e.g., frequent muscle cramps, myalgia, fibromyalgia) or sleep related disorders (e.g. sleep apnea, unless on stable Continuous Positive Airway Pressure [CPAP]) which may confound the outcome measures.
- Subjects with multiple sclerosis.
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 |
|---|---|---|
| InjectaferAlso: Ferinject®, Iroprem®, Renegy® | Drug | Injectafer |
| PlaceboAlso: Normal Saline | Other | Normal Saline |
Primary outcome
International Restless Legs Syndrome (IRLS) Total Score Change From Baseline on Day 42
Time frame: Baseline and Day 42
Summary of the actual values of IRLS total score on baseline and Day 42, and the change from baseline to Day 42. Eligible subjects were to have met the following requirements prior to receiving additional treatment: A baseline score ≥ 15 on the International Restless Legs Syndrome (IRLS) Rating Scale. The minimum score is 15 with the maximum of 40. A score of less than 15 is not an indicator of RLS. However, a score of 15 or greater is an indicator of RLS. Further increase indicates more severe disease.
Proportion of Patients Rated as Much or Very Much Improved With the Clinical Global Impression (CGI) Performed by Investigator (CGI-I)
Time frame: Day 42
Responder is defined as subjects rated as much or very much improved with the CGI-I on Day 42. Summary of the number (percentage) of CGI-I responder. Per the protocol, the he CGI is a 3-item observer-rated scale that measures illness severity (CGIS), global improvement or change (CGIC) and therapeutic response. The scale requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.
5 secondary outcomes
Clinical Global Impression-Improvement (CGI-S) by Subject
Time frame: Day 42
Restless Legs Syndrome Quality of Life (RLS-QLI) Change From Baseline to Day 42.
Time frame: Baseline and Day 42
Fatigue Linear Analog Scale Change From Baseline
Time frame: Baseline and Day 42
Medical Outcomes Study(MOS) Sleep Scale Change From Baseline to Day 42
Time frame: Change from Baseline and Day 42.
Time Off Pre-Enrollment Prescribed Restless Legs Syndrome (RLS) Medications
Time frame: Time from Day 5 to Day 365
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38625730Earley CJ, Garcia-Borreguero D, Falone M, Winkelman JW. Clinical efficacy and safety of intravenous ferric carboxymaltose for treatment of restless legs syndrome: a multicenter, randomized, placebo-controlled clinical trial. Sleep. 2024 Jul 11;47(7):zsae095. doi: 10.1093/sleep/zsae095.
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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.
Mark Falone, MD study director
American Regent, Inc.
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Injectafer in people with Restless Legs Syndrome (RLS), run by American Regent, Inc. at 19 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 11 inclusion and 26 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: finished, as of the sponsor's last update on 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 12 Oct 2021). 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?
International Restless Legs Syndrome (IRLS) Total Score Change From Baseline on Day 42 (time frame: Baseline and Day 42). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02397057, which also lists 1 linked publication.
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 12 Oct 2021.