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

• ClinicalTrials.gov Identifier: NCT03813160
• Recruitment Status: Active, not recruiting
• First Posted: January 23, 2019
• Last Update Posted: August 13, 2020
• Sponsor: Corbus Pharmaceuticals Inc.
• Information provided by (Responsible Party): Corbus Pharmaceuticals Inc.

Study Description

Brief Summary:

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 treatment with study drug is 52 weeks.

Condition or disease	Intervention/treatment	Phase
Dermatomyositis	Drug: Lenabasum 20 mg; Drug: Lenabasum 5 mg; Drug: Placebo	Phase 3

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 52 will be 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 176 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate Efficacy and Safety of Lenabasum in Dermatomyositis
• Actual Study Start Date: December 17, 2018
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: September 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Efficacy of lenabasum compared to placebo as measured by Total Improvement Score (TIS) [ Time Frame: Week 52 ]
   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.

Secondary Outcome Measures :

1. Efficacy of lenabasum compared to placebo as measured by Mean MMT-8 Score [ Time Frame: Week 52 ]
   Strength in 8 muscle groups will be assessed on a 0 - 10 point scale; lower score is "weaker" and higher score is "stronger."
2. Efficacy of lenabasum compared to placebo as measured by Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score [ Time Frame: Week 52 ]
   The CDASI is a validated outcome measure that systematically quantifies cutaneous DM activity. Disease involvement in 15 different anatomical locations is rated using three activity (erythema, scale, erosion/ulceration) and two damage (poikiloderma, calcinosis) measures. The presence and severity of Gottron's papules, periungual changes and alopecia are also captured. Disease activity is scored from 0 to 100; higher scores indicate greater disease severity.
3. Efficacy of lenabasum compared to placebo as measured by Investigator Global Assessment (IGA) scale of skin activity [ Time Frame: Week 52 ]
   The IGA is used by the investigator to score overall skin disease on a 0 to 4 scale; higher scores indicate greater skin disease.
4. Efficacy of lenabasum compared to placebo as measured by Short Form-36 (SF-36) physical functioning domain score [ Time Frame: Week 52 ]
5. Efficacy of lenabasum compared to placebo as measured by corticosteroid dose [ Time Frame: Week 52 ]
6. Efficacy of lenabasum compared to placebo as measured by Forced Vital Capacity (FVC) % predicted [ Time Frame: Week 52 ]
7. Safety of lenabasum compared to placebo as measured by Adverse Events (AEs) associated with lenabasum treatment [ Time Frame: From initiation of treatment (Day 1) to end of treatment (Week 52) ]
8. Tolerability of lenabasum compared to placebo as measured by number of subjects who permanently discontinue study product due to AEs probably- or definitely-related to treatment [ Time Frame: From initiation of treatment (Day 1) to end of treatment (Week 52) ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Fulfill 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 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

Contacts and Locations

Locations

United States, Arizona

HonorHealth Neurology

Phoenix, Arizona, United States, 85018

Mayo Clinic

Scottsdale, Arizona, United States, 85259

United States, California

Attune Health Center

Beverly Hills, California, United States, 90211

UCLA Division of Rheumatology

Los Angeles, California, United States, 90095

United States, Colorado

Denver Arthritis Clinic

Denver, Colorado, United States, 80230

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States, 20001

United States, Florida

Mayo Clinic

Jacksonville, Florida, United States, 32224

University of Miami

Miami, Florida, United States, 33136

University of South Florida

Tampa, Florida, United States, 33612

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Louisiana

DelRicht Research

New Orleans, Louisiana, United States, 70115

United States, Maryland

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States, 21224

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

University of Minnesota, Division of Rheumatic and Autoimmune Diseases

Minneapolis, Minnesota, United States, 55455

United States, Missouri

Washington University in St. Louis

Saint Louis, Missouri, United States, 63110

United States, New York

Hospital for Special Surgery

New York, New York, United States, 10021

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh, Division of Rheumatology

Pittsburgh, Pennsylvania, United States, 15261

United States, South Carolina

MUSC: Department of Neurology

Charleston, South Carolina, United States, 29425

United States, Texas

Austin Neuromuscular Center

Austin, Texas, United States, 78756

United States, Wisconsin

Rheumatic Disease Center

Glendale, Wisconsin, United States, 53217

Bulgaria

University Hospital "Kaspela" Rheumatology Clinic

Plovdiv, Bulgaria

UMHAT "St. Ivan Rilski"

Sofia, Bulgaria

UMHAT

Stara Zagora, Bulgaria, 6000

Canada, British Columbia

University of British Columbia, Dept. of Dermatology and Skin Science

Vancouver, British Columbia, Canada, V5Z 4E8

Czechia

Revmatologicky ustav

Prague, Czechia, 12850

Germany

Charite-Universitatsmedizin

Berlin, Germany

University Hospital Erlangen Nuremberg

Erlangen, Germany, D- 91054

University Medical Center Goettingen

Göttingen, Germany

Hungary

University of Debrecen

Debrecen, Hungary

Italy

University Hospital Policlinico-Vittorio Emanuele

Catania, Italy, 95121

Fondazione Policlinico Universitario A.Gemelli-IRCCS

Roma, Italy, 00168

Japan

Gunma University Hospital

Gunma, Japan

Hokkaido University Hospital

Hokkaido, Japan

Yokohama City University Hospital

Kanagawa, Japan

Kyoto University Hospital

Kyoto, Japan

Tohoku University Hospital

Miyagi, Japan

Osaka University Hospital

Osaka, Japan

Keio University Hospital

Tokyo, Japan

Nippon Medical School Hospital

Tokyo, Japan

Wakayama Medical Hospital

Wakayama, Japan

Korea, Republic of

Inha University Hospital

Incheon, Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Hanyang University Hospital

Seoul, Korea, Republic of

Seoul St. Mary's Hospital

Seoul, Korea, Republic of

Poland

KLIMED

Bialystok, Poland

Kliniczny Szpital Wojewodzki Nr 1. im Fryderyka Chopina Klinika Dermatologii

Rzeszow, Poland, 35-055

KLIMED

Łomża, Poland, 18-404

Spain

Vall d'Hebron General Hospital

Barcelona, Spain

Hospital 12 Octubre

Madrid, Spain

Sweden

Karolinska University Hospital, Rheumatology Clinic

Stockholm, Sweden

United Kingdom

King's College Hospital NHS Foundation Trust

London, United Kingdom

Sponsors and Collaborators

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

More Information

• Responsible Party: Corbus Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03813160
• Other Study ID Numbers: JBT101-DM-002
• First Posted: January 23, 2019
• Last Update Posted: August 13, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Corbus Pharmaceuticals Inc.:

dermatomyositis; cannabinoid receptor type 2 agonist; JBT-101; lenabasum

Additional relevant MeSH terms:

Dermatomyositis; Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin Diseases