Trial to Evaluate Efficacy and Safety of Lenabasum in Diffuse Cutaneous Systemic Sclerosis (RESOLVE-1)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate Efficacy and Safety of Lenabasum in Diffuse Cutaneous Systemic Sclerosis

This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study assessing the efficacy and safety of lenabasum for the treatment of diffuse cutaneous systemic sclerosis (SSc). Approximately 354 subjects will be enrolled in this study at about 60 sites in North America, Europe, Australia, and Asia. The planned duration of treatment with study drug is 52 weeks.

Study Overview

• Status: Terminated
• Conditions: Diffuse Cutaneous Systemic Sclerosis
• Intervention / Treatment: Drug: Lenabasum 5 mg; Drug: Lenabasum 20 mg; Other: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Actual): 365
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Liverpool, Australia
    • Liverpool Hospital
  • Melbourne, Australia, 3065
    • St Vincent's Hospital
  • Sydney, Australia
    • Royal Prince Alfred Hospital
• Canada
  • Montréal, Canada
    • Sir Mortimer B. Davis Jewish General Hospital
  • Winnipeg, Canada
    • The Arthritis Centre
• Germany
  • Berlin, Germany
    • Charité- Universitätsmedizin Berlin, Klinik für Rheumatologie und Klinische Immunologie, Abteilung -Neue Therapien & Studien-
  • Cologne, Germany
    • University Hospital Cologne, Department of Dermatology and Venereology
  • Erlangen, Germany
    • Department of Internal Medicine 3, University of Erlangen-Nuremberg
  • Freiburg, Germany
    • University Medical Center Freiburg
  • Köln, Germany
    • Universitätsklinik Köln,Klinik und Poliklinik für Dermatologie und Venerologie
  • Nauheim, Germany
    • Kerckhoff-Klinik GmbH, Zentrum Rheumatologie u. Klin. Immunologie, Studienambulanz
  • Ulm, Germany
    • University Hospital Ulm
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Universitätsklinikum Heidelberg
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Corporation
  • Haifa, Israel
    • Bnai Zion Medical Center
  • Kefar Saba, Israel
    • Meir Medical Center - Internal Medicine E
  • Ramat Gan, Israel
    • Sheba Medical Center
• Japan
  • Fukuoka, Japan
    • Kyushu University Hospital
  • Kanazawa, Japan
    • Kanazawa University Hospital
  • Maebashi, Japan
    • Gunma University Hospital
  • Sapporo, Japan
    • Hokkaido University Hospital
  • Sendai, Japan
    • National University Corporation Tohoku University Tohoku University Hospital
  • Suita, Japan
    • Osaka University Hospital
  • Tokyo, Japan
    • Nippon Medical School Hospital
  • Yokohama, Japan
    • Yokohama City University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of
    • Hanyang University Medical Center
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • The Hague, Netherlands
    • Haga Hospital
  • South Holland
    • Leiden, South Holland, Netherlands
      • Leiden University Medical Center
• Poland
  • Lublin, Poland
    • Samodzielny Publiczny Szpital Kliniczny nr 1; Katedra i Klinika Dermatologii, Wenerologii i Dermatologii Dziecięcej Uniwersytetu Medycznego w Lublinie
  • Poznań, Poland
    • Medyczne Centrum Hetmańska
  • Wrocław, Poland
    • Reum-Medica S.C
• Spain
  • Barcelona, Spain
    • Hospital Universitari de la Santa Creu i Sant Pau
  • Valencia, Spain
    • Hospital Universitario Doctor Peset
• Switzerland
  • Saint Gallen, Switzerland
    • Cantonal Hospital St. Gallen
  • Zürich, Switzerland
    • University Hospital Zurich
• United Kingdom
  • Leeds, United Kingdom
    • Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM)
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital London NHS Foundation Trust
  • London, United Kingdom
    • Guy's and St.Thomas' NHS Foundation Trust
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Ninewells Hospital
  • Tyne And Wear
    • Newcastle, Tyne And Wear, United Kingdom, NE7 7DN
      • Freeman Hospital
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Russell's Hall Hospital
• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • Los Angeles, California, United States, 90095
      • UCLA
    • Los Angeles, California, United States, 90045
      • Pacific Arthritis Care Center
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • John Hopkins University, Scleroderma Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, Division of Rheumatology
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center (BUMC) - General Clinical Research Unit (GCRU)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Health Clinical research unit
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Clinical Research Center, Robert Wood Johnson Medical School
  • New York
    • Albany, New York, United States, 12203
      • The Steffens Scleroderma at The Center for Rheumatology
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Hospital for Special Surgery
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Toledo, Ohio, United States, 43614
      • University of Toledo
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System - PCAM, Dept. of Rheumatology
    • Pittsburgh, Pennsylvania, United States, 15261
      • UPMC Arthritis and Autoimmunity Center, Falk Clinic
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center
    • Houston, Texas, United States, 77030
      • UTP Rheumatology Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospitals and Clinics
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin/Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. ≥ 18 years of age at the time Informed Consent is signed.
2. Diffuse cutaneous SSc (skin thickening on upper arms, upper legs, or trunk).
3. Disease duration ≤ 6 years from the first non-Raynaud's symptom.
4. No new or increased doses of immunosuppressive medications within 8 weeks prior to Screening.

Key Exclusion Criteria:

1. Unstable SSc or SSc with end-stage organ involvement at Screening or Visit 1.

2. Any of the following values for laboratory tests at Screening:

   1. A positive pregnancy test in women of childbearing potential;
   2. Hemoglobin < 9 g/dL for males and < 8 g/dL for females;
   3. Neutrophils < 1.0 ×10^9/L;
   4. Platelets < 75 ×10^9/L;
   5. Creatinine clearance < 50 mL/min according to the Modification of Diet in Renal Disease (MDRD) Study equation;
   6. Aspartate aminotransferase or alanine aminotransferase > 2.0 × upper limit of normal.
3. Any medical condition or concurrent medical therapies at Screening or Visit 1, including a history of non-compliance with medical treatments, that may put the subject at greater safety risk, influence response to study product, or interfere with study assessments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Lenabasum 5 mg BID	Drug: Lenabasum 5 mg; Subjects will receive lenabasum 5 mg twice daily.
Experimental: Cohort 2; Lenabasum 20 mg BID	Drug: Lenabasum 20 mg; Subjects will receive lenabasum 20 mg twice daily.
Placebo Comparator: Cohort 3; Placebo BID	Other: Placebo oral capsule; Subjects will receive placebo twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of lenabasum compared to placebo for the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis score.	The ACR CRISS exponential algorithm determines the predicted probability of improvement from baseline, incorporating change in mRSS, FVC % predicted, physician and patient global assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A higher score indicates greater improvement.	American College of Rheumatology Combined Response Index score through study completion, up to 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of lenabasum compared to placebo for the change from baseline in modified Rodnan skin score.	mRSS evaluates a subject's skin thickness on a 4 point scale for 17 surface anatomic areas: 0 = normal skin; 1 = mild thickness; 2 = moderate thickness; 3 = severe thickness with inability to pinch skin into fold. The individual values of the 17 surface areas are summed to define the total skin score with a maximum score of 51.	Change from baseline through study completion, up to 1 year.
Efficacy of lenabasum compared to placebo for the change from baseline in Health Assessment Questionnaire - Disability Index.	It includes 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). The individual scores of the eight sections are summed and divided by 8. The result is the disability index or functional disability index. A higher score indicates more functional disability.	Change from baseline through study completion, up to 1 year.
Efficacy of lenabasum compared to placebo for the change from baseline in forced vital capacity.		Change from baseline through study completion, up to 1 year.

Collaborators and Investigators

• Sponsor: Corbus Pharmaceuticals Inc.
• Investigators: Principal Investigator: Robert Spiera, MD, Professor of Clinical Medicine, Weill Cornell Medical College; Principal Investigator: Chris Denton, MD, Professor of Experimental Rheumatology and Consultant Rheumatologist and Centre Head, Royal Free Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2017
• Primary Completion (Actual): May 27, 2020
• Study Completion (Actual): December 21, 2020

Study Registration Dates

• First Submitted: January 5, 2018
• First Submitted That Met QC Criteria: January 11, 2018
• First Posted (Actual): January 16, 2018

Study Record Updates

• Last Update Posted (Actual): March 29, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Scleroderma; cannabinoid receptor type 2 agonist; JBT-101; lenabasum; anabasum
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol; Lenabasum
• Other Study ID Numbers: JBT101-SSc-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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