Trial to Evaluate Efficacy and Safety of Lenabasum in Dermatomyositis (DETERMINE)

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

This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study assessing the efficacy and safety of lenabasum for the treatment of dermatomyositis. Approximately 150 subjects will be enrolled in this study at about 60 sites in North America, Europe, and Asia. The planned duration of double-blind treatment with study drug is up to 52 weeks.

Study Overview

• Status: Completed
• Conditions: Dermatomyositis
• Intervention / Treatment: Drug: Placebo; Drug: Lenabasum 20 mg; Drug: Lenabasum 5 mg

Detailed Description

Subjects will be randomized to receive lenabasum 20 mg twice per day, lenabasum 5 mg twice per day, or placebo twice per day in a 2:1:2 ratio. The primary efficacy outcome at Week 28 will compare lenabasum 20 mg BID to placebo the Total Improvement Score (TIS), which is a weighted composite measure of improvement from baseline in six endpoints: Physician Global Assessment of Disease Activity, Physician Assessment of Extramuscular Disease Activity, Patient Global Assessment of Disease Activity, Health Assessment Questionnaire (patient-reported disability), Manual Muscle Testing (MMT), and muscle enzymes.

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • University Hospital "Kaspela" Rheumatology Clinic
  • Sofia, Bulgaria
    • UMHAT "St. Ivan Rilski"
  • Stara Zagora, Bulgaria, 6000
    • UMHAT
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E8
      • University of British Columbia, Dept. of Dermatology and Skin Science
• Czechia
  • Prague, Czechia, 12850
    • Revmatologicky ustav
• Germany
  • Berlin, Germany
    • Charité-Universitätsmedizin
  • Erlangen, Germany, D- 91054
    • University Hospital Erlangen Nuremberg
  • Göttingen, Germany
    • University Medical Center Goettingen
• Hungary
  • Debrecen, Hungary
    • University of Debrecen
• Italy
  • Catania, Italy, 95121
    • University Hospital Policlinico-Vittorio Emanuele
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A.Gemelli-IRCCS
• Japan
  • Gunma, Japan
    • Gunma University Hospital
  • Hokkaido, Japan
    • Hokkaido University Hospital
  • Kanagawa, Japan
    • Yokohama City University Hospital
  • Kyoto, Japan
    • Kyoto University Hospital
  • Miyagi, Japan
    • Tohoku University Hospital
  • Osaka, Japan
    • Osaka University Hospital
  • Tokyo, Japan
    • Keio University Hospital
  • Tokyo, Japan
    • Nippon Medical School Hospital
  • Wakayama, Japan
    • Wakayama Medical Hospital
• Korea, Republic of
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Seoul st. mary's hospital
  • Seoul, Korea, Republic of
    • Hanyang University Hospital
• Poland
  • Bialystok, Poland
    • KLIMED
  • Rzeszow, Poland, 35-055
    • Kliniczny Szpital Wojewodzki Nr 1. im Fryderyka Chopina Klinika Dermatologii
  • Łomża, Poland, 18-404
    • KLIMED
• Spain
  • Barcelona, Spain
    • Vall d'Hebron General Hospital
  • Madrid, Spain
    • Hospital 12 Octubre
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital, Rheumatology Clinic
• United Kingdom
  • London, United Kingdom
    • King's College Hospital NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • HonorHealth Neurology
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Beverly Hills, California, United States, 90211
      • Attune Health Center
    • Los Angeles, California, United States, 90095
      • UCLA Division of Rheumatology
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Arthritis Clinic
  • District of Columbia
    • Washington, District of Columbia, United States, 20001
      • Georgetown University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Research
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, Division of Rheumatic and Autoimmune Diseases
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh, Division of Rheumatology
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC: Department of Neurology
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Neuromuscular Center
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Rheumatic Disease Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Fulfill at least one of the following criteria for dermatomyositis:

  1. Bohan and Peter criteria (Bohan and Peter, 1975a; Bohan and Peter 1975b)
  2. ACR/EULAR criteria (Lundberg et al, 2017)

• Disease activity/severity fulfills at least one of the following three criteria:

  1. MDGA ≥ 3 cm (0 - 10 cm Visual Analog Scale [VAS]) and MMT-8 score ≤ 142 (out of 150 total possible)
  2. Sum of MDGA, PtGA and EMGA VAS scores is ≥ 10 cm (0-10 cm VAS for each)
  3. MDGA ≥ 3 cm (0-10 cm VAS) and CDASI activity score of > 14

• Stable doses of immunosuppressive medications for DM as defined by:

  1. Unchanged dose of oral corticosteroids ≤ 20 mg per day prednisone or equivalent for ≥ 4 weeks before Visit 1
  2. Unchanged dose of immunosuppressive medications other than oral corticosteroids for ≥ 8 weeks before Screening

Exclusion Criteria:

• Unstable DM or DM with end-stage organ involvement at Screening or Visit 1
• Significant diseases or conditions other than DM that may influence response to the study drug or safety

• Any of the following values for laboratory tests at Screening:

  1. A positive pregnancy test (or at Visit 1)
  2. Hemoglobin < 9 g/dL in males and < 8 g/dL in females
  3. Neutrophils < 1.0 × 10^9/L
  4. Platelets < 75 × 10^9/L
  5. Creatinine clearance < 50 mL/min on screening blood test, per the Modification of Diet in Renal Disease Study or in 24 hour urine creatine clearance measurement

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: Lenabasum 20 mg; Subjects will receive lenabasum 20 mg twice daily	Drug: Lenabasum 20 mg; oral capsule; Other Names: JBT-101; anabasum
Experimental: Lenabasum 5 mg; Subjects will receive lenabasum 5 mg twice daily	Drug: Lenabasum 5 mg; oral capsule; Other Names: JBT-101; anabasum
Placebo Comparator: Placebo; Subjects will receive placebo twice daily	Drug: Placebo; oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of lenabasum 20 mg BID compared to placebo BID as measured by Total Improvement Score (TIS)	TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis.	Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects who achieve Definition of Improvement (DOI)	Defined as ≥ 3 of 6 core set measures improved by ≥ 20% (relative to Baseline) with no more than 2 core set measures worsening by ≥ 25% (MMT-8 may not decrease by ≥ 25% from baseline)	Week 28
Subjects who improve by at least one category on the Investigator Global Assessment (IGA) scale of skin activity	The IGA is used by the investigator to score overall skin disease on a 0 to 4 scale; higher scores indicate greater skin disease.	Week 28
Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score	CDASI is a validated outcome measure that systematically quantifies cutaneous DM disease activity and damage (Klein et al, 2007; Yassaee et al, 2010) Disease Activity Score is rated using three activity measures. The activity score ranges from 0 to 100. Higher scores indicate greater disease severity.	Week 28
Subjects who achieve TIS >= 40 (at least moderate improvement)	TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis.	Week 28
TIS in subjects receiving immunosuppressive therapies (including corticosteroids) for > 1 year at Baseline	TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis.	Week 52
Change in Forced vital capacity (FVC) absolute, in all subjects and those with interstitial lung disease (ILD) at Baseline.	ILD is defined as a history of fibrosis on chest x-ray, a history of ILD on CT of lungs, and/or FVC% predicted <80% at Screening or Visit 1	Week 28
Change in Forced vital capacity (FVC) percent predicted, in all subjects and those with interstitial lung disease (ILD) at Baseline.	ILD is defined as a history of fibrosis on chest x-ray, a history of ILD on CT of lungs, and/or FVC% predicted <80% at Screening or Visit 1	Week 28
TIS at Visit 10	TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis.	Week 52
TIS, lenabasum 5 mg BID versus placebo	TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis.	Week 28

Collaborators and Investigators

• Sponsor: Corbus Pharmaceuticals Inc.
• Investigators: Principal Investigator: Victoria P Werth, MD, University of Pennsylvania; Principal Investigator: Chester V Oddis, MD, University of Pittsburgh Department of Medicine/Division of Rheumatology

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2018
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): October 5, 2021

Study Registration Dates

• First Submitted: January 21, 2019
• First Submitted That Met QC Criteria: January 21, 2019
• First Posted (Actual): January 23, 2019

Study Record Updates

• Last Update Posted (Actual): August 16, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: dermatomyositis; cannabinoid receptor type 2 agonist; JBT-101; lenabasum
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Polymyositis; Myositis; Dermatomyositis; 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-DM-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