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

Sponsor

Elorac, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02811783

Collaborator

(none)

160

Enrollment

Locations

Arms

78.9

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Mycosis Fungoides Lymphoma, T-Cell, Cutaneous Sézary Syndrome	Drug: Naloxone Hydrochloride Lotion, 0.5% Drug: Placebo Lotion	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Naloxone Hydrochloride Lotion, 0.5% Naloxone Hydrochloride Lotion 0.5%	Drug: Naloxone Hydrochloride Lotion, 0.5% Topical TID for 2 weeks
Placebo Comparator: Placebo Lotion Placebo Lotion	Drug: Placebo Lotion Topical TID for 2 weeks

Arm

Intervention/Treatment

Active Comparator: Naloxone Hydrochloride Lotion, 0.5%

Naloxone Hydrochloride Lotion 0.5%

Drug: Naloxone Hydrochloride Lotion, 0.5%

Topical TID for 2 weeks

Placebo Comparator: Placebo Lotion

Placebo Lotion

Drug: Placebo Lotion

Topical TID for 2 weeks

Outcome Measures

Primary Outcome Measures

Numeric Rating Scale (NRS) for Pruritus [Baseline and 2 Weeks]
Change from Baseline to Day 14 in average NRS for Pruritus for each Treatment Period

Secondary Outcome Measures

Responder Analysis - The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. [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 [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 [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 [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) [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Signed informed consent has been obtained.
Subject is at least 21 years of age.
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).
Completion of the mSWAT assessment.
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.

Pruritic treatment area of 5-95% of the subject's total treatable body surface area.
Subject can be expected to reliably follow treatment instructions and visit schedule.
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.
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.
Subject has no visual or motor impairments that will make it difficult to complete the Daily Diary or apply the study medication.
Subject is able to speak, read, and write English and agrees to participate and comply with the study procedures.
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:

Pregnant or lactating female.
History of clinically significant heart failure.
Myocardial infarction within the past six months.
A history of ventricular arrhythmia requiring treatment.
Any medical condition which would, in the Investigator's opinion, preclude the subject from successfully participating in the study.
A known allergy to naloxone hydrochloride or any excipient in the formulation.
Previous naloxone use for pruritus.
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.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Medical Center	Birmingham	Alabama	United States	35233
2	Mayo Clinic	Scottsdale	Arizona	United States	85259
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	City of Hope	Duarte	California	United States	91010
5	Stanford University	Palo Alto	California	United States	94304
6	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
7	USSF Health Morsani Center for Advanced Healthcare	Tampa	Florida	United States	33612
8	Cleveland Clinic Indian River Hospital	Vero Beach	Florida	United States	32960
9	Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois	United States	60611
10	Rush University Medical Center	Chicago	Illinois	United States	60612
11	The University of Chicago Medicine	Chicago	Illinois	United States	60637
12	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana	United States	46250
13	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
14	Massachusetts General Hospital CURTIS	Boston	Massachusetts	United States	02114
15	Boston Medical Center	Boston	Massachusetts	United States	02118
16	University of Minnesota	Minneapolis	Minnesota	United States	55455
17	St. Louis University Dermatology	Saint Louis	Missouri	United States	63104
18	Washington University School of Medicine St. Louis	Saint Louis	Missouri	United States	63110
19	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
20	Columbia University Medical Center	New York	New York	United States	10032
21	Stony Brook Dermatology	Stony Brook	New York	United States	11790
22	Duke University Medical Center	Durham	North Carolina	United States	27710
23	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
24	Ohio State University, James and Solove Research and Cancer Hospital	Columbus	Ohio	United States	43210
25	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
26	Jefferson Dermatology Associates	Philadelphia	Pennsylvania	United States	19107
27	UPMC Department of Dermatology	Pittsburgh	Pennsylvania	United States	15213
28	Vanderbilt Dermatology	Nashville	Tennessee	United States	37204
29	University of Texas South Western Medical Center	Dallas	Texas	United States	75390
30	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
31	Inova Schar Cancer Institute	Fairfax	Virginia	United States	22031
32	University of Washington / Seattle Cancer Care Alliance (SCCA)	Seattle	Washington	United States	98109