Clinical trial NCT02397057: Placebo-Controlled Study to Investigate the Efficacy & Safety of Injectafer in the Treatment of RLS
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Restless Legs Syndrome (RLS)
Lead sponsor: American Regent, Inc.
Sponsor class: INDUSTRY
First posted: 2015-03-24
Enrollment: 209
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female subject's ≥18 years of age, willing and able to give informed consent to the study.
2. RLS symptoms affirming diagnosis. The IRLS Diagnostic Criteria must be met:

   1. 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.
   2. The urge to move or unpleasant sensations are worse or exclusively present at rest or inactivity, such as lying down or sitting.
   3. The urge to move or unpleasant sensations are partially/temporarily relieved with walking or moving the legs.
   4. 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.
3. 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).
4. A score ≥15 on the IRLS Rating Scale at screening and on Day 0 prior to dosing.
5. Subjects on anti-depressants and sleep medications must be on a stable dose for at least 6 months.
6. Subject has regular sleep hours between 9 pm and 9 am.
7. 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.

Exclusion Criteria:

1. RLS 2° to other disease or injury.
2. Disorders that require treatment with the same medications used for RLS include: peripheral neuropathy and neurodegenerative disorders (i.e. Parkinson's Disease or Dementia).
3. Stage 4 - 5 CKD, subjects on dialysis or anticipated to start dialysis while participating in this study.
4. 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.
5. Subjects with multiple sclerosis.
6. History of neuroleptic akathisia.
7. Parenteral iron use within 6 weeks prior to screening.
8. History of \>10 blood transfusions in the past 2 years.
9. Anticipated need for blood transfusion during the study.
10. Known hypersensitivity reaction to any component of Injectafer® (Ferric Carboxymaltose).
11. Previously randomized to Injectafer® (FCM or VIT-45) in a clinical trial.
12. Current, active or acute or chronic infection other than viral upper respiratory tract infection
13. Malignancy (other than basal or squamous cell skin cancer or the subject has been cancer free for ≥ 5 years).
14. Pregnant or lactating women.
15. Seizure disorder currently being treated with medication.
16. Baseline ferritin ≥300 ng/mL.
17. Baseline TSAT ≥45%.
18. History of hemochromatosis, hemosiderosis, or other iron storage disorders.
19. AST or ALT greater than 2 times the upper limit of normal (ULN).
20. Hemoglobin greater than the ULN.
21. 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).
22. Known positive HIV-1/HIV-2 antibodies (anti-HIV).
23. Received an investigational drug within 30 days before randomization.
24. Chronic alcohol or drug abuse within the past 6 months.
25. 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.
26. Subject unable or unwilling to comply with the study requirements.

Primary outcomes:
measure: International Restless Legs Syndrome (IRLS) Total Score Change From Baseline on Day 42
timeFrame: Baseline and Day 42
measure: Proportion of Patients Rated as Much or Very Much Improved With the Clinical Global Impression (CGI) Performed by Investigator (CGI-I)
timeFrame: Day 42
Secondary outcomes:
measure: Clinical Global Impression-Improvement (CGI-S) by Subject
timeFrame: Day 42
measure: Restless Legs Syndrome Quality of Life (RLS-QLI) Change From Baseline to Day 42.
timeFrame: Baseline and Day 42
measure: Fatigue Linear Analog Scale Change From Baseline
timeFrame: Baseline and Day 42
measure: Medical Outcomes Study(MOS) Sleep Scale Change From Baseline to Day 42
timeFrame: Change from Baseline and Day 42.
measure: Time Off Pre-Enrollment Prescribed Restless Legs Syndrome (RLS) Medications
timeFrame: Time from Day 5 to Day 365
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research, Inc.
state: Alabama
city: National City
country: United States
facility: Synergy San Diego
state: California
city: Rancho Mirage
country: United States
facility: Desert Valley Research
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: Boca Raton
country: United States
facility: Neurology Offices of South FL
state: Florida
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
city: Lenexa
country: United States
facility: MidAmmerica Neuroscience Institute
state: Kansas
city: Lexington
country: United States
facility: Central Kentucky Research Assoc., Inc.
state: Kentucky
city: Alexandria
country: United States
facility: Neuromedical Clinical of Central Louisiana
state: Louisiana
city: Fulton
country: United States
facility: Ctr for Brain & Neuro Care, LLC
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital, Sleep Disorders Clinical Research Program
state: Massachusetts
city: Las Vegas
country: United States
facility: Desert Neurology
state: Nevada
city: Las Vegas
country: United States
facility: Neurology Center of Las Vegas
state: Nevada
city: Greensboro
country: United States
facility: Guilford Neurologic Associates
state: North Carolina
city: Indian Land
country: United States
facility: Metrolina Neurological Associates
state: South Carolina
city: Spartanburg
country: United States
facility: Saad Upstate Neurology
state: South Carolina
city: Johnson City
country: United States
facility: Tri-State Mountain Neurology Associates
state: Tennessee
city: Houston
country: United States
facility: Egret Bay Neurology
state: Texas
city: Seattle
country: United States
facility: The Polyclinic, Madison Center
state: Washington
Study officials:
affiliation: American Regent, Inc.
name: Mark Falone, MD
role: STUDY_DIRECTOR
References: