Naloxone Hydrochloride Study for Relief of Pruritus in Patients With MF or SS Forms of CTCL

• ClinicalTrials.gov Identifier: NCT02811783
• Recruitment Status: Recruiting
• First Posted: June 23, 2016
• Last Update Posted: January 19, 2022
• Sponsor: Elorac, Inc.
• Information provided by (Responsible Party): Elorac, Inc.

Tracking Information

• First Submitted Date: June 15, 2016
• First Posted Date: June 23, 2016
• Last Update Posted Date: January 19, 2022
• Actual Study Start Date: January 2017
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2016)

Numeric Rating Scale (NRS) for Pruritus [ Time Frame: Baseline and 2 Weeks ]

Change from Baseline to Day 14 in average NRS for Pruritus for each Treatment Period

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 26, 2017)

• Responder Analysis - The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. [ Time Frame: Baseline and 2 Weeks ]
  The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. A clinically significant improvement is defined as an improvement of at least one category on the 4-point (none, mild, moderate, severe) Likert Scale verbal rating scale (VRS) and at least two points on the 11-point NRS for Pruritus. The NRS for Pruritus scores will be converted to VRS scores as follows for the analysis: 0=none, 1-3=mild, 4-6=moderate, and 7-10=severe.
• Numeric Rating Scale for Sleep [ Time Frame: Baseline and 1 and 2 weeks ]
  The change from Baseline at each week of the NRS for Sleep average score for each Treatment Period.
• Numeric Rating Scale for Pruritus [ Time Frame: Baseline and 1 week ]
  The change from Baseline at Week 1 of the NRS for Pruritus average score for each Treatment Period.
• Categorical Rating Scale (CRS) for Skin Integrity [ Time Frame: Baseline and 2 weeks ]
  The change from Baseline at Week 2 of the CRS for Skin Integrity for each Treatment Period.
• Pruritus Quality of Life Score (PQOL) [ Time Frame: Baseline and Day 14 of each Treatment period ]
  The change from Baseline in the final categorization of the PQOL at Day 14 of each Treatment Period

Original Secondary Outcome Measures (submitted: June 22, 2016)

• Responder Analysis - The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. [ Time Frame: Baseline and 2 Weeks ]
  The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. A clinically significant improvement is defined as an improvement of at least one category on the 4-point (none, mild, moderate, severe) Likert Scale verbal rating scale (VRS) and at least two points on the 11-point NRS for Pruritus. The NRS for Pruritus scores will be converted to VRS scores as follows for the analysis: 0=none, 1-3=mild, 4-6=moderate, and 7-10=severe.
• Numeric Rating Scale for Sleep [ Time Frame: Baseline and 1 and 2 weeks ]
  The change from Baseline at each week of the NRS for Sleep average score for each Treatment Period.
• Numeric Rating Scale for Pruritus [ Time Frame: Baseline and 1 week ]
  The change from Baseline at Week 1 of the NRS for Pruritus average score for each Treatment Period.
• Categorical Rating Scale (CRS) for Skin Integrity [ Time Frame: Baseline and 2 weeks ]
  The change from Baseline at Week 2 of the CRS for Skin Integrity for each Treatment Period.

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

Descriptive Information

• Brief Title: Naloxone Hydrochloride Study for Relief of Pruritus in Patients With MF or SS Forms of CTCL
• Official Title: A Double Blind Randomized Vehicle Controlled Crossover Study to Evaluate the Safety and Efficacy of Topical Naloxone Hydrochloride Lotion 0.5% for the Relief of Pruritus in Patients With the MF or SS Forms of Cutaneous T-Cell Lymphoma

Brief Summary

This multi-center, double-blind, vehicle-controlled, randomized crossover design study will evaluate the safety and efficacy of topically applied naloxone lotion, 0.5%, for the treatment of pruritus in patients with the mycosis fungoides (MF) or Sézary syndrome (SS) Forms of Cutaneous T-cell Lymphoma (CTCL). This study will also determine if there is systemic absorption of the drug in a subset of subjects and if so, describe the range and mean plasma levels reached after two weeks of three time daily (TID) dosing.

Funding Source - FDA OOPD

• Detailed Description: There will be 160 subjects enrolled in the study. The study consists of a Screening Period of up to 7 days during which inclusion / exclusion criteria will be reviewed. Subjects meeting inclusion / exclusion criteria including the diagnostic criteria for MF or SS and a score of at least 5 on the 11-Point Numeric Rating Scale (NRS) for Pruritus will complete the one week Screening Period. Subjects will complete a daily diary for NRS for Pruritus scores and Sleep scores. At the end of the Screening Period, subjects who have a NRS for Pruritus score of at least 5 recorded in the diary on at least 4 of the 7 days preceding Day 0 will be eligible to continue. Baseline assessments will be recorded for vital signs, pruritic body surface area, skin integrity, PQOL, and laboratory results. The Baseline period will be followed by a 2 week Treatment Period 1 in which subjects will be randomized to Naloxone Lotion 0.5% or Placebo Lotion to be applied TID for 14 days. During the 2 week Treatment Period subjects will complete daily diaries of NRS for Pruritis scores and Sleep scores. On Day 14 subjects will return to the clinic to review diaries, adverse events (AEs), concomitant medications, and to record body surface area for pruritus, skin integrity, PQOL, and laboratory results. Subjects will then enter a Washout Period for up to 56 days until the subject again scores at least 5 on the NRS for Pruritus on 4 consecutive or 4 of the past 7 days or 56 days pass. Subjects will then enter a 2 week Treatment Period 2 during which the same procedures as Treatment Period 1 will be performed except subjects will receive the alternate treatment to that assigned in Treatment Period 1. Subjects will then have the option to enter a 26 Week Open Label Treatment Period 3 during which the same procedures as Treatment Period 1 and 2 will be performed except subjects will return only at Week 13 and Week 26 and all subjects will be treated with Naloxone Lotion 0.5%.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Mycosis Fungoides
• Lymphoma, T-Cell, Cutaneous
• Sézary Syndrome

Intervention

• Drug: Naloxone Hydrochloride Lotion, 0.5%
  Topical TID for 2 weeks
• Drug: Placebo Lotion
  Topical TID for 2 weeks

Study Arms

• Active Comparator: Naloxone Hydrochloride Lotion, 0.5%
  Naloxone Hydrochloride Lotion 0.5%
  Intervention: Drug: Naloxone Hydrochloride Lotion, 0.5%
• Placebo Comparator: Placebo Lotion
  Placebo Lotion
  Intervention: Drug: Placebo Lotion

• Publications *: Valipour A, Jäger M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7:CD008946. doi: 10.1002/14651858.CD008946.pub3.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 22, 2016): 160
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

All subjects must meet the following criteria for admission into the study:

1. Signed informed consent has been obtained.
2. Subject is at least 21 years of age.
3. Diagnosis of mycosis fungoides (MF) or Sézary syndrome (SS) will be based on a combination of histological, clinical, and immunophenotypical criteria. The histological criteria will be based on skin biopsy from the most representative skin area. The diagnostic criteria used for each subject will be specified in the case report forms and the specific classification of MF or SS will be identified. The TNMB system will be used to classify the stage of disease (See Section 8.4 for details).
4. Completion of the mSWAT assessment.

5. A history of pruritus that meets following criteria:

   At Screening Day -7:

   • present on a daily basis for greater than one month prior to Screening Day -7,
   • NRS for Pruritus score ≥5 as rated by the subject at the Day -7 Visit. Note: If the score is <5 and subject is taking or has taken a medication which may be affecting pruritus (e.g. systemic antihistamine or topical steroid), and if Investigator and subject agree, subject may washout or continue washout of medication and return for Day -7 Visit procedures after washout.

   At Baseline Period 1 Day 0:

   • NRS for Pruritus score of at least 5 recorded in the subject diary on at least 4 of the 7 days preceding Baseline Period 1 Day 0.
6. Pruritic treatment area of 5-95% of the subject's total treatable body surface area.
7. Subject can be expected to reliably follow treatment instructions and visit schedule.
8. Non-pregnant, non-lactating females of childbearing potential who agree to use medically acceptable forms of birth control (abstinence, hormonal contraceptives, diaphragm with spermicide, condom with spermicide, or intrauterine device) throughout the study or females of non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal ligation] or post-menopausal ≥ 1 year). A negative urine pregnancy test must be confirmed at Baseline screening for all female subjects who are not post-menopausal > 1 year or surgically sterile.
9. The subject agrees not to begin any new concomitant medications during their participation in the study, with the exception of medications necessary to treat infection, and to continue any concomitant medication throughout the study.
10. Subject has no visual or motor impairments that will make it difficult to complete the Daily Diary or apply the study medication.
11. Subject is able to speak, read, and write English and agrees to participate and comply with the study procedures.
12. Subject has a body mass index (BMI) between 18.5 and 30.5 kglm2 (see Appendix C, Body Mass Index Table) (subjects in PK subset only).

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from study participation:

1. Pregnant or lactating female.
2. History of clinically significant heart failure.
3. Myocardial infarction within the past six months.
4. A history of ventricular arrhythmia requiring treatment.
5. Any medical condition which would, in the Investigator's opinion, preclude the subject from successfully participating in the study.
6. A known allergy to naloxone hydrochloride or any excipient in the formulation.
7. Previous naloxone use for pruritus.
8. Positive urine drug screen at Day 0 for opiates. Positive urine drug screen for anything other than opiates not explained, e.g., by concomitant medication, would also exclude the subject.
9. Treatment with any of the following during the restricted time period prior to Day -7, and at any time during the study, is not allowed:

Medication/Treatment Restriction:

Systemic narcotic analgesics (e.g. morphine, codeine) 7 days, Topical antihistamines to any skin surface [e.g. Zonalon® (doxepin)] 7 days, Other investigational drugs (excluding any therapies for the treatment of MF or SS) 30 days

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Scott B Phillips, MD; 8473628200; scott@eloracpharma.com

Contact: Heidi Fezatte, BS; 8473628200; hfezatte@eloracpharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02811783
• Other Study ID Numbers: EL-1007-01-01; 1R01FD005396-01A1 ( U.S. FDA Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Elorac, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Elorac, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Scott B Phillips, MD; Elorac, Inc.

• PRS Account: Elorac, Inc.
• Verification Date: January 2022