A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE (RIFLE)

A Randomized, Double-Blind, Active Comparator-Controlled, Crossover Study to Assess the Capacity of RAYOS® Compared to Immediate-Release Prednisone to Improve Fatigue and Control Morning Symptoms in Subjects With Systemic Lupus Erythematosus

To compare the effect of RAYOS® versus immediate-release (IR) prednisone on fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).

Study Overview

• Status: Completed
• Conditions: Fatigue; Lupus Erythematosus, Systemic; Lupus Erythematosus
• Intervention / Treatment: Drug: RAYOS; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095
      • The Regents of the University of California, Los Angeles
    • Orange, California, United States, 92868
      • University of California-Irvine
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92037
      • The Regents of the University of California, San Diego
    • San Francisco, California, United States, 94143
      • University of California-San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
    • Miami, Florida, United States, 33136
      • Miller School of Medicine at the University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01605
      • UMASS Memorial Medical Center-Memorial Campus
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • The Hospital for Special Surgery
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • The MetroHealth System
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide written informed consent agreeing to all study procedures, before any study-specific procedures are done.
2. Males or non-pregnant females, aged 18 years or older
3. Diagnosis of SLE by either the American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics Classification (SLICC) criteria
4. Fatigue measured by FACIT-F ≤30.
5. On a stable regimen of IR prednisone (5 to 15 mg/day) for a period of at least 30 days prior to Screening, expected to remain stable for the next 6 months.

6. On a stable SLE treatment regimen for a period of at least 30 days prior to Screening, and expected to remain stable for the next 6 months. Any of the following medications are permitted if stable for at least 30 days prior to Screening and expected to remain stable for the next 6 months:

   • Hydroxychloroquine or equivalent anti-malarial
   • Other immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate sodium or mycophenylate mofetil at no more than 2 grams/day), belimumab, cyclophosphamide, calcineurin inhibitors (e.g. tacrolimus, cyclosporine)
7. Entry of daily ePRO data on 11 of 14 days during the baseline period, and completion of at least 6 out of the 8 weekly ePRO questionnaires during the baseline period
8. Willing and able to perform and comply with all study procedures, including taking pills daily as prescribed, completing the ePROs on the smart phone, wearing the smart watch day and night, bringing the smartphone on all activities away from home (e.g., walks, errands, visiting, shopping, traveling), keeping the smartphone and smartwatch charged daily, carefully using the smartphone and smartwatch as clinical tools and keeping them secure from others, and attending monthly clinic visits as scheduled
9. Females of childbearing potential must be currently using a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with vasectomized partner, hysterectomy, bilateral tubal ligation, licensed hormonal methods, intrauterine device, or use of a spermicide combined with a barrier method (e.g., condom, diaphragm) for 30 days before and 90 days after receiving the study drug

Exclusion Criteria:

1. Previously taken any of the following medications:

   • RAYOS®
   • Rituximab within 6 months prior to Screening
   • Any investigational therapy within 3 months or 5 half-lives of the agent prior to Screening
2. History of noncompliance with taking pills as prescribed.
3. Rapidly progressive neurologic disease
4. Rapidly progressive renal disease (defined by proteinuria >6 g/24 hours or equivalent using spot urine protein to creatinine ratio, or serum creatinine >2.5 mg/dL)
5. Diagnosis of fibromyalgia

6. Any of the following clinical laboratory abnormalities:

   • Hemoglobin <8.0 mg/dL
   • Platelet count <50,000/mm3
   • White blood count (WBC) ≤ 2000/mm3; may be 1999-1000/mm3 if stable and related to SLE
   • Absolute neutrophil count (ANC) ≤1000/mm3; may be 500-999/mm3 if stable and related to SLE
   • Aspartate transaminase (AST) or alanine transaminase (ALT) ≥3× upper limit of normal (ULN) unless related to SLE
   • Calculated creatinine clearance ≤25 mL/min per 1.73 m2 (by Cockcroft-Gault equation)

7. Grade 3 or greater laboratory abnormality based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; Appendix 3) except for the following that are allowed:

   • Activated partial thromboplastin time (PTT) > >2.5× ULN due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy
   • Hypoalbuminemia <2 g/dL due to chronic lupus nephritis, and not related to liver disease
   • Gamma glutamyl transferase (GGT) <20× ULN due to lupus hepatitis, and not related to alcoholic liver disease, uncontrolled diabetes, or viral hepatitis. If present, any abnormalities in the ALT and/or AST must be ≤5× ULN
8. Pregnant or nursing, or females not using effective contraception
9. Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 1 year prior to Screening
10. Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not caused by SLE (e.g., diabetes, cardiovascular, pulmonary, hematologic, gastrointestinal, neurological, or infectious) which, in the opinion of the Investigator, could confound the results of the study or put the subject at undue risk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAYOS®	Drug: RAYOS; FDA approved RAYOS for indication of fatigue in Lupus.
Active Comparator: IR prednisone	Drug: Prednisone; FDA approved corticosteroid frequently used for SLE.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue	Fatigue as measured in FACIT-F by patient	3 months

Collaborators and Investigators

• Sponsor: Ampel BioSolutions, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2017
• Primary Completion (Actual): May 28, 2019
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: March 21, 2017
• First Submitted That Met QC Criteria: March 28, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): July 8, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Fatigue; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: AMP-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No