A Study of Rotigotine Patch in Adolescent Subjects With Restless Legs Syndrome of Unknown Cause

• ClinicalTrials.gov Identifier: NCT03728933
• Recruitment Status: Terminated
• First Posted: November 2, 2018
• Results First Posted: October 26, 2023
• Last Update Posted: October 26, 2023
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Tracking Information

• First Submitted Date: October 31, 2018
• First Posted Date: November 2, 2018
• Results First Submitted Date: October 5, 2023
• Results First Posted Date: October 26, 2023
• Last Update Posted Date: October 26, 2023
• Actual Study Start Date: December 20, 2018
• Actual Primary Completion Date: July 25, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2023)

• Change From Baseline to the End of the Maintenance Period in International Restless Legs Rating Scale (IRLS) Sum Score [ Time Frame: From Baseline to the end of the Maintenance Period (Day 106) ]
  The IRLS consisted of 10 questions, each scored using a 5-point scale ranging from 0=not present to 4=very severe. The IRLS sum score was calculated by summing up the single scores of all applicable questions, i.e., the total sum score ranged from 0 (no RLS symptoms present) to 40 (maximum severity in all symptoms). A score between 31 and 40, indicates very severe RLS. A score between 21 and 30 indicates severe RLS. A score between 11 and 20 indicates moderate RLS. A score between 1 and 10 indicates mild RLS and a score of 0 means no RLS. A negative change from Baseline indicates improvement.
• Change From Baseline in Clinical Global Impressions (CGI) Item 1 to the End of the Maintenance Period [ Time Frame: From Baseline to the end of the Maintenance Period (Day 106) ]
  The Clinical Global Impressions Item 1 (Severity of Illness) score ranges from 0 to 7 as follows: 0=not assessed, 1=normal, not ill at all, 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill. The CGI Item 1 was completed during an interview between the participant and the investigator or designee. A negative change from Baseline indicates improvement.
• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From Baseline to Safety Follow-Up (up to Week 20) ]
  TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (i.e., on or after the date of first patch application and within 30 days following the date of last patch removal + 1 day), or those events where the intensity worsened within this time frame.
• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawals [ Time Frame: From Baseline to Safety Follow-Up (up to Week 20) ]
  TEAEs were defined as events that started during the Treatment Period or within 30 days following the end of the Treatment Period (i.e., on or after the date of first patch application and within 30 days following the date of last patch removal + 1 day), or those events where the intensity worsened within this time frame.

Original Primary Outcome Measures (submitted: October 31, 2018)

• Change from Baseline to the end of the Maintenance Period in International Restless Legs Rating Scale (IRLS) sum score [ Time Frame: From Baseline to the end of the Maintenance Period (Day 78) ]
  The sum score ranges from 0 (no RLS symptoms present) to 40 (maximum severity in all symptoms), which is the maximum score. A score between 31 and 40, indicates very severe RLS. A score between 21 and 30 indicates severe RLS. A score between 11 and 20 indicates moderate RLS. A score between 1 and 10 indicates mild RLS and a score of 0 means no RLS.
• Change from Baseline in Clinical Global Impressions (CGI) Item 1 to the end of the Maintenance Period [ Time Frame: From Baseline to the end of the Maintenance Period (Day 78) ]
  The Clinical Global Impressions Item 1 (Severity of Illness) score ranges from 0 to 7 as follows: 0=not assessed, 1=normal, not ill at all, 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill. The CGI Item 1 is to be completed during an interview between the subject and the investigator or designee.

Current Secondary Outcome Measures (submitted: October 5, 2023)

Change From Baseline in Restless Legs-6 Rating Scales (RLS-6) to the End of the Maintenance Period [ Time Frame: From Baseline to the end of the Maintenance Period (Day 106) ]

The RLS-6 Rating Scales was designed to assess the severity of RLS and consisted of 6 subscales. The subscales assessed severity of symptoms at the following times of the day/evening: falling asleep, during the night, during the day at rest, and during the day when engaged in daytime activities. In addition, the subscales assessed satisfaction with sleep and severity of daytime tiredness/sleepiness. Scores for each of the 6 subscales ranged from 0 (completely satisfied) to 10 (completely dissatisfied). The change from baseline was derived for each of the subscales and reported in this outcome measure. A negative change from Baseline indicates improvement.

Original Secondary Outcome Measures (submitted: October 31, 2018)

Change from Baseline in Restless Legs-6 Rating Scales (RLS-6) to the end of the Maintenance Period [ Time Frame: From Baseline to the end of the Maintenance Period (Day 78) ]

The RLS-6 Rating Scales is designed to assess the severity of RLS and consists of 6 subscales. The subscales assess severity of symptoms at the following times of the day/evening: falling asleep, during the night, during the day at rest, and during the day when engaged in daytime activities. In addition, the subscales assess satisfaction with sleep and severity of daytime tiredness/sleepiness.Scores for each of the 6 subscales range from 0 (completely satisfied) to 10 (completely dissatisfied).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Rotigotine Patch in Adolescent Subjects With Restless Legs Syndrome of Unknown Cause
• Official Title: A Remote, Double-Blind, Randomized, Placebo-Controlled Study of Rotigotine Transdermal System in Adolescent Subjects With Idiopathic Restless Legs Syndrome
• Brief Summary: The purpose of this study is to demonstrate the efficacy of rotigotine against placebo in adolescent subjects with idiopathic Restless Legs Syndrome (RLS) over a 12-week maintenance period and to investigate the safety and tolerability of rotigotine in adolescent subjects with idiopathic RLS.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Restless Legs Syndrome

Intervention

• Drug: Rotigotine 1 milligram/24 hours
  Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: Application of rotigotine transdermal patch with 1 milligram (mg)/24 hours (h) (5 square centimeter (cm^2) patch size).
  Other Name: Neupro
• Drug: Rotigotine 2 milligram/24 hours
  Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: Application of rotigotine transdermal patch with 2 milligram (mg)/24 hours (h) (10 square centimeter (cm^2) patch size).
  Other Name: Neupro
• Drug: Placebo
  Pharmaceutical Form: transdermal patch Route of administration: transdermal use Concentration: not applicable

Study Arms

• Experimental: 2 milligram/24 hours rotigotine
  Subjects randomized to this arm will be initiated on 1 milligram (mg)/24 hours (h) rotigotine and up-titrated to a maximum of 2 mg/24 h rotigotine, which is the assigned dose level throughout the 12-week Maintenance Period.
  Interventions:

  • Drug: Rotigotine 1 milligram/24 hours
  • Drug: Rotigotine 2 milligram/24 hours
• Experimental: 3 milligram/24 hours rotigotine
  Subjects randomized to this arm will be initiated on 1 milligram (mg)/24 hours (h) rotigotine and up-titrated to a maximum of 3 mg/24 h rotigotine (1 mg/24 h patch + 2 mg/24 patch at the same time), which is the assigned dose level throughout the 12-week Maintenance Period.
  Interventions:

  • Drug: Rotigotine 1 milligram/24 hours
  • Drug: Rotigotine 2 milligram/24 hours
• Placebo Comparator: Placebo
  Subjects randomized to this arm will receive matching placebo patches to maintain the blinding.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 6, 2023): 23
• Original Estimated Enrollment (submitted: October 31, 2018): 138
• Actual Study Completion Date: July 25, 2022
• Actual Primary Completion Date: July 25, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject is male or female, and is >=13 and <18 years of age at Baseline
• Subject's Restless Legs Syndrome (RLS) symptoms cause significant daytime symptoms or significant distress or impairment in social, occupational, educational, or other important areas of functioning by the impact on sleep, energy/vitality, daily activities, behavior, cognition or mood
• At Baseline, subject has a score of >=15 on the International Restless Legs Rating Scale (IRLS) (indicating moderate-to-severe RLS)
• At Baseline, subject scores >=4 points on the Clinical Global Impressions (CGI) Item 1 assessment (indicating at least moderately ill)
• Subjects who are receiving supplemental iron have been on a stable dose for at least 1 month prior to Screening
• Female subjects must be surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and spermicide). Abstinence is an acceptable method. Subjects must agree to use adequate contraception during the study and for 4 weeks after their final dose of study medication.

Exclusion Criteria:

• Subject has a serum ferritin level below the lower limit of normal at Visit 1/Screening
• Subject has a hemoglobin level below the lower limit of normal at Visit 1/Screening
• Subject has had previous treatment with dopamine agonists or L-dopa within 7 days prior to Visit 2/Baseline
• Subject has any medical or psychiatric condition, which in the opinion of the investigator, would jeopardize or compromise the subject's well-being or ability to participate in this study
• Subject is pregnant or nursing
• Subject is not willing to abstain from caffeine after 4 pm each evening within 7 days prior to Visit 2/Baseline and for the duration of the study
• At Visit 1/Screening, subject has symptomatic orthostatic hypotension with a decrease of blood pressure (BP) from supine to standing position of >=20 mmHg in systolic blood pressure (SBP) or of >=10 mmHg in diastolic
• Subject has secondary Restless Legs Syndrome (RLS) (eg, due to renal insufficiency [uremia], iron deficiency, or rheumatoid arthritis)
• Subject has a lifetime history of suicide attempts (including actual attempt, interrupted attempt, or aborted attempt), or had suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1)
• Subject is taking a prohibited concomitant medication. Prohibited concomitant medication must have been discontinued at least 2 weeks prior to Screening (Visit 1)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 13 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03728933
• Other Study ID Numbers: SP1006
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed.All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• URL: https://vivli.org

• Current Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• Original Responsible Party: UCB Biopharma S.P.R.L.
• Current Study Sponsor: UCB Biopharma SRL
• Original Study Sponsor: UCB Biopharma S.P.R.L.
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; 001 844 599 2273

• PRS Account: UCB Pharma
• Verification Date: September 2023