Trial to Evaluate Efficacy and Safety of Lenabasum in Dermatomyositis

Dermatomyositis Clinical Trial

— DETERMINE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03813160
• Other study ID #: JBT101-DM-002
• Status: Completed
• Phase: Phase 3
• Start date: December 17, 2018
• Est. completion date: October 5, 2021

Study information

• Verified date: August 2022
• Source: Corbus Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 double-blind treatment with study drug is up to 52 weeks.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: October 5, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dermatomyositis

Intervention

Drug:
• Lenabasum 20 mg
oral capsule
• Lenabasum 5 mg
oral capsule
• Placebo
oral capsule

Locations

Country	Name	City	State
Bulgaria	University Hospital "Kaspela" Rheumatology Clinic	Plovdiv
Bulgaria	UMHAT "St. Ivan Rilski"	Sofia
Bulgaria	UMHAT	Stara Zagora
Canada	University of British Columbia, Dept. of Dermatology and Skin Science	Vancouver	British Columbia
Czechia	Revmatologicky ustav	Prague
Germany	Charite-Universitatsmedizin	Berlin
Germany	University Hospital Erlangen Nuremberg	Erlangen
Germany	University Medical Center Goettingen	Göttingen
Hungary	University of Debrecen	Debrecen
Italy	University Hospital Policlinico-Vittorio Emanuele	Catania
Italy	Fondazione Policlinico Universitario A.Gemelli-IRCCS	Roma
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
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Hanyang University Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Poland	KLIMED	Bialystok
Poland	KLIMED	Lomza
Poland	Kliniczny Szpital Wojewodzki Nr 1. im Fryderyka Chopina Klinika Dermatologii	Rzeszow
Spain	Vall d'Hebron General Hospital	Barcelona
Spain	Hospital 12 Octubre	Madrid
Sweden	Karolinska University Hospital, Rheumatology Clinic	Stockholm
United Kingdom	King's College Hospital NHS Foundation Trust	London
United States	University of Michigan	Ann Arbor	Michigan
United States	Austin Neuromuscular Center	Austin	Texas
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Attune Health Center	Beverly Hills	California
United States	MUSC: Department of Neurology	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Rheumatic Disease Center	Glendale	Wisconsin
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	UCLA Division of Rheumatology	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	University of Minnesota, Division of Rheumatic and Autoimmune Diseases	Minneapolis	Minnesota
United States	DelRicht Research	New Orleans	Louisiana
United States	Hospital for Special Surgery	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	HonorHealth Neurology	Phoenix	Arizona
United States	University of Pittsburgh, Division of Rheumatology	Pittsburgh	Pennsylvania
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Mayo Clinic	Scottsdale	Arizona
United States	University of South Florida	Tampa	Florida
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Corbus Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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