JBT-101 in Systemic Lupus Erythematosus (SLE)

A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus Erythematosus

The objective of this study is to evaluate the efficacy, safety, and tolerability of JBT-101 (also known as lenabasum) in systemic lupus erythematosus (SLE).

• One hundred adults with active joint disease and at least moderate pain will be enrolled in this study to evaluate treatment of their systemic lupus erythematosus (SLE) with JBT-101. JBT-101 is a synthetic endocannabinoid receptor type 2 (CB2) agonist and an activator of the body's normal processes, to resolve innate immune responses without immunosuppression.
• Participants will receive 2 doses of JBT-101 by mouth (three groups of varying doses) or, placebo, for 84 days and will continue to be followed for an additional 28 days. Participant visits to assess endpoints occur on Day 1, then every 2 weeks twice, then every 4 weeks three times, for a total of six visits.
• The change in maximum daily pain Numerical Rating Scale (NRS) score from Baseline (Visit 1) will be assessed at every visit.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus; SLE; Lupus
• Intervention / Treatment: Drug: JBT-101; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego School of Medicine: Division of Rheumatology, Allergy and Immunology
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center: Division of Rheumatology
    • San Francisco, California, United States, 94143
      • University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University: Division of Rheumatology
  • New York
    • Bronx, New York, United States, 10457
      • Bronx-Lebanon Hospital Center: Division of Rheumatology
    • Manhasset, New York, United States, 11030
      • Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
    • New York, New York, United States, 10016
      • New York University Langone Medical Center: Department of Medicine, Division of Rheumatology
    • New York, New York, United States, 10032
      • Columbia University Medical Center: Department of Medicine, Division of Rheumatology
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State MS Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Pittsburgh, Pennsylvania, United States, 15217
      • University of Pittsburgh Medical Center: Division of Rheumatology and Clinical Immunology
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Fulfills the updated American College of Rheumatology (ACR) 1982 Revised Criteria for the Classification of Systemic Lupus Erythematosus;
• At least 3 months of treatment with an anti-malarial drug such as hydroxychloroquine or a history of intolerance, contraindication, or unwillingness to take an anti-malarial drug;
• Meets the Safety of Estrogen in Lupus: National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) definition of arthritis (Petri et al., 1999) or mild/moderate arthritis or tendonitis scored as a BILAG B on the updated BILAG 2004;
• Seven-day average of maximum of daily pain Numerical Rating Scale (NRS) scores ≥ 4 out of 10;
• Overlap with polymyositis, systemic sclerosis, Sjögren's syndrome, or rheumatoid arthritis is allowed, if, in the site investigator's judgment, the predominant clinical features are those of Systemic Lupus Erythematosus (SLE);
• Not expected by the site investigator to require a change in potential disease- modifying treatments for SLE from Screening through Visit 6 (Day 112);
• Willing to not start nor stop any Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or potential disease-modifying medications or supplements for SLE from Screening through Visit 6 (Day 112), unless a change is recommended by the site investigator or other treating physicians;
• Willing not to use any legal or illegal cannabinoids, including Food and Drug Administration (FDA)-approved cannabinoids or cannabinoid-mimic drugs, or any illegal substance of abuse from Screening through Visit 6 (Day 112);
• If a woman of child-bearing potential, willing to use one of the highly effective (failure rate < 1% per year) birth control method from Screening through Visit 6 (Day 112) or for 28 ± 3 days after the last dose of study product; and
• Willing to follow instructions, complete study procedures and attend study visits as required by this protocol.

Exclusion Criteria:

• Severe or unstable Systemic lupus erythematosus (SLE), such as any one of the following:

  • A British Isles Lupus Activity Group (BILAG) A score in one or more BILAG domains at Screening;
  • Treatment with any intraarticular, intravenous, or intramuscular systemic corticosteroids within 14 days of Screening;
  • Treatment with oral prednisone > 10 mg per day or > 20 mg every other day (or equivalent dose of another corticosteroid) within 14 days of Screening;
  • Increased dose of systemic corticosteroids in the 14 days prior to Screening;
  • Treatment with cyclophosphamide or anti-TNFalpha biologic agents within 3 months before Visit 1 (Day 1);
  • Treatment with B cell-depleting monoclonal antibodies (rituximab, Ocrelizumab, anti-CD22) within 6 months before Visit 1 (Day 1);
  • Treatment with methotrexate, mycophenolate, azathioprine, leflunomide, cyclosporine, belimumab, tacrolimus, or any other immunosuppressive agent not included in 2b.-d. above, when the dose of that immunosuppressive agent has increased within 3 months before Visit 1. Concurrent treatment with any of these medications is allowed as long as the doses have been stable for at least 3 months before Visit 1 (Day 1); or
  • Actively listed on an organ transplantation list or have received an organ transplant other than a corneal transplant.

• Significant diseases or conditions other than SLE that may influence response to the study product or safety, such as:

  • Active bacterial or viral infection requiring systemic antibiotic or anti-viral treatment within 14 days before Visit 1 (Day 1);
  • Acute or chronic hepatitis B or C infection;
  • Human immunodeficiency infection (HIV);
  • History of active tuberculosis or positive tuberculosis skin or blood test without: 1) completing a course of appropriate treatment; or ) having received at least one month of appropriate treatment prior to Visit 1 (Day 1) and continuing to receive appropriate treatment during the study;
  • No elective surgery should be planned from Visit 1 (Day 1) through Visit 6 (Day 112); or
  • A history of cancer except basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy greater than one year before Visit 1 (Day 1).

  • Significant heart disease as defined by:

    • Uncontrollable congestive heart failure, unstable angina, unstable atherosclerotic cardiovascular disease, significant arrhythmia requiring chronic therapy, pulmonary arterial hypertension with dyspnea, disability rated as New York heart Association Grade III or higher, severe systemic hypertension or severe peripheral vascular disease;
    • Marked baseline prolongation of QT/QTc interval (i.e. repeated demonstration of a QTc interval ≥ 450 msec for males and ≥470 msec for females);
    • History of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT/QTc syndrome); or
    • Clinically significant confirmed abnormality, as determined by the site investigator or qualified designee, on 12-lead Electrocardiogram (ECG) at Screening or Visit 1 (Day 1) before dosing.
• History of chronic pain requiring treatment with narcotic analgesia for more than 14 days total within 6 months of baseline. This does not include self-limited pain associated with identifiable events such as surgery;
• Current evidence of alcohol abuse (defined as 4 or more drinks per day on at least 4 days of the week) or history of abuse of illegal and/or legally prescribed drugs such as barbiturates, benzodiazepines, amphetamines, cocaine, or opioids during the 1 year prior to Screening;
• Currently pregnant, breast-feeding, or lactating;
• Any investigational agent within 30 days or five therapeutic half-lives of that agent whichever is longer, before Visit 1 (Day 1);

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

  • A positive pregnancy test (also at Visit 1);
  • A newly positive QuantiFERON(R) blood test for tuberculosis, without: 1) completing a course of appropriate treatment; or ) having received at least one month of appropriate treatment prior to Visit 1 and continuing to receive appropriate treatment during the study. If the subject has a previous documented positive tuberculosis skin, then this testing does not need to be repeated. If the subject has a documented negative test result within the last year, testing does not need to be repeated, at the discretion of the site investigator.
  • Hemoglobin < 8 g/dL;
  • Neutrophils < 1.0 x 10^9/L;
  • Platelets < 75 x 10^9/L;
  • Estimated Glomerular Filtration Rate (eGFR) < 50 ml/min according to Cockcroft-Gault equation;
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase > 2.0 x upper limit of normal; or
  • Total bilirubin ≥ 1.5 x upper limit of normal.
• Any other conditions that, in the opinion of the site investigator, are clinically significant and may put the subject at greater safety risk, influence response to study product, or interfere with study assessments. When in doubt, the site investigator or qualified designee should discuss the situation with the Protocol Chairs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JBT-101: 5 mg Twice Daily; Eligible subjects will receive assigned study treatment of JBT-101 5 mg administered twice daily.	Drug: JBT-101; Participants will self-administer JBT-101 by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.; Other Names: anabasum; lenabasum; resunab; ajulemic acid; CT-3; IP751; CPL7075
Experimental: JBT-101: 20 mg & Placebo; Eligible subjects will receive assigned study treatment of JBT-101 20 mg (A.M. Study Product) and 20 mg Placebo (P.M. Study Product).	Drug: JBT-101; Participants will self-administer JBT-101 by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.; Other Names: anabasum; lenabasum; resunab; ajulemic acid; CT-3; IP751; CPL7075; Drug: Placebo; Participants will self-administer JBT-101 placebo by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.; Other Names: JBT-101 placebo; lenabasum placebo
Experimental: JBT-101: 20 mg Twice Daily; Eligible subjects will receive assigned study treatment of JBT-101 20 mg (A.M. Study Product) and JBT-101 20 mg (P.M. Study Product).	Drug: JBT-101; Participants will self-administer JBT-101 by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.; Other Names: anabasum; lenabasum; resunab; ajulemic acid; CT-3; IP751; CPL7075
Placebo Comparator: Placebo + Placebo; Eligible subjects will receive assigned study treatment of Placebo (A.M.) and Placebo (P.M.) for (JBT-101).	Drug: Placebo; Participants will self-administer JBT-101 placebo by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.; Other Names: JBT-101 placebo; lenabasum placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in the Maximum Daily NRS-Pain Score at Day 84	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. Participants will be asked to report their maximum daily pain using the NRS-Pain. Participants will call into an interactive voice response e diary system (IVRS) and record the number that best reflects their maximum amount of pain experienced in the last 24 hours. Participants will be asked to call at the same time each day, preferably before bedtime. Longitudinal trends over the course of the treatment period will be modeled and used to estimate difference between means at baseline and Day 84 for each treatment group.	Day 1 through Day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With No Pain, Mild Pain, Moderate Pain or Severe Pain in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain.	Visit 1 (Baseline)
Number of Participants With No Pain, Mild Pain, Moderate Pain or Severe Pain in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain.	Visit 3 (Day 29)
Number of Participants With No Pain, Mild Pain, Moderate Pain or Severe Pain in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain.	Visit 4 (Day 57)
Number of Participants With No Pain, Mild Pain, Moderate Pain or Severe Pain in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain.	Visit 5 (Day 85)
Number of Participants With No Pain, Mild Pain, Moderate Pain or Severe Pain in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain.	Visit 6 (Day 113)
Change From Baseline in the Improvement Pain Category Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The Improvement Pain Category is the change in the pain category from baseline to the post-baseline visit. An improvement of at least 2 pain categories from baseline is considered major pain improvement; improvement of 1 pain category, improvement; no change in pain category, no change; worsening of at least 1 pain category, worsening.	Visit 3 (Day 29)
Change From Baseline in the Improvement Pain Category Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The Improvement Pain Category is the change in the pain category from baseline to the post-baseline visit. An improvement of at least 2 pain categories from baseline is considered major pain improvement; improvement of 1 pain category, improvement; no change in pain category, no change; worsening of at least 1 pain category, worsening.	Visit 4 (Day 57)
Change From Baseline in the Improvement Pain Category Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The Improvement Pain Category is the change in the pain category from baseline to the post-baseline visit. An improvement of at least 2 pain categories from baseline is considered major pain improvement; improvement of 1 pain category, improvement; no change in pain category, no change; worsening of at least 1 pain category, worsening.	Visit 5 (Day 85)
Change From Baseline in the Improvement Pain Category Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The Improvement Pain Category is the change in the pain category from baseline to the post-baseline visit. An improvement of at least 2 pain categories from baseline is considered major pain improvement; improvement of 1 pain category, improvement; no change in pain category, no change; worsening of at least 1 pain category, worsening.	Visit 6 (Day 113)
Percentage of Participants Who Had at Least 30% Improvement From Baseline in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The percent change from baseline in the 7-day average of the maximum NRS-Pain scores prior to study Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment) and Visit 6 (Day 113)
Percentage of Participants Who Had at Least 50% Improvement From Baseline in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The percent change from baseline in the 7-day average of the maximum NRS-Pain scores prior to study Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment) and Visit 6 (Day 113)
Percentage of Participants Who Had at Least 75% Improvement From Baseline in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits Score	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The percent change from baseline in the 7-day average of the maximum NRS-Pain scores prior to study Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment) and Visit 6 (Day 113)
Percentage of Participants Who Had 100% Improvement From Baseline in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits	The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The percent change from baseline in the 7-day average of the maximum NRS-Pain scores prior to study Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment) and Visit 6 (Day 113)
Change From Baseline in Physician Assessed Tender Joint Count	The change from baseline in the number of tender joints identified by the physician in the Physician Joint Exam at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed. The number of tender joints can range from 0 to 68 joints.	Baseline, (Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment
Change From Baseline in Physician Assessed Swollen Joint Count	The change from baseline in the number of swollen joints identified by the physician in the Physician Joint Exam at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed. The number of swollen joints can range from 0 to 66 joints.	Baseline, (Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Percentage of Participants With Presence of Arthritis in SELENA-SLEDAI	The Safety of Estrogen in Lupus National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is a validated tool for assessing SLE disease activity. The percentage of participants with arthritis indicated as Present on the SELENA SLEDAI at Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed. [A single question on the SELENA SLEDAI with a response of Present or Absent was assessed.]	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment) and Visit 6 (Day 113)
Percentage of Participants With Improvement From Baseline in Arthritis in BILAG-2004	The BILAG-2004* is a validated index for assessing SLE disease activity. The BILAG-2004 includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems. The severity of arthritis at baseline will be determine by the highest arthritis severity level where arthritis is indicated as improving, same, new or worse* BILAG-2004: British Isles Lupus Assessment Group 2004. The percentage of participants who met the criteria for improvement of arthritis in the BILAG-2004 Musculoskeletal assessments (using the mild, moderate and severe arthritis questions on the assessment) at Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment) and Visit 6 (Day 113)
Percentage of Participants as Responders Using the SLE Responder Index (SRI)	The SRI is a validated SLE disease activity instrument used to detect clinically meaningful improvement of disease in SLE clinical trials. The SRI is a composite instrument comprised of the SELENA-SLE Disease Activity Index [SELENA-SLEDAI], Physician Global Assessment (PGA) and British Isles Lupus Assessment Group (BILAG) 2004. A responder is defined as having at least a 4 point reduction in the SELENA-SLEDAI score, no new BILAG A or no more than 1 new BILAG B domain score, and no increase in the PGA of 0.3 points or more. The percentage of participants who met the criteria for a responder in the SRI at Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment) and Visit 6 (Day 113)
Change From Baseline in Lupus Disease Activity - SELENA-SLEDAI Score	The change from baseline in the SELENA-SLEDAI score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed. The Safety of Estrogen in Lupus National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is a validated tool for assessing SLE disease activity. The SLEDAI is a one page assessment that contains 24 items scored as present or absent. Each item is assigned a weighted score which is summed to calculate the overall SLEDAI score. SLEDAI score ranges from 0-105 points. Higher scores represent more disease activity, with a score of 6 being considered clinically important and may impact the decision to treat.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change From Baseline in Lupus Disease Activity - Total BILAG-2004 Score	For each of the nine domains, a numerical score will be assigned based on the BILAG score as follows: A=12, B=8, C=1 and D/E=0. A single numerical BILAG total score will be calculated for each participant visit as the summation of the numerical scores for each of the nine domains. The BILAG total score can range from 0 to 108, with higher scores indicating more disease activity. The change from baseline in the total BILAG-2004 score at Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed. The BILAG-2004* is a validated index for assessing SLE disease activity. The BILAG-2004 includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems. * BILAG-2004: British Isles Lupus Assessment Group 2004.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change From Baseline in Lupus Disease Activity -Physician's Global Assessment (PGA) Score	The change from baseline in the total PGA score at Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed. The PGA utilizes a 0 to 3 visual analogue scale for assessing disease activity in SLE that is anchored by the verbal descriptors as follows: 0 = none, 1 = mild, 2 = moderate, 3 = severe. An increase of >=0.3 points is considered worsening of the PGA.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change From Baseline in Lupus Disease Activity- Patient Global Assessment Score	The change from baseline in the total Patient Global Assessment score at Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed. The total Patient Global Assessment is performed with a visual analogue scale (0 to 100) in which the participant is asked to indicate how active she/he thinks their disease is. The visual analogue scale is anchored by two descriptors: "not active" (score of 0) and "extremely active" (score of 100).	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment) and Visit 6 (Day 113)
Change in Baseline in PROMIS-29 Short Form Score - Physical Function T-score	The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Short Form (Version 2.0) will be used to assess trends over time in this state of health measure. The PROMIS-29 consists of 7 domains related to physical, mental and social health. Raw scores are calculated for each domain and translated into a T-score per the PROMIS-29 scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. A higher score represents better functioning for the Physical Function domain. The change from baseline in the PROMIS-29 Physical Function T-score at Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85).	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85 - Last Day of Treatment)
Change in Baseline in PROMIS - Anxiety T-Score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank version 2.0 - Anxiety T-Score will be used to assess trends over time in this health measure. The raw score is calculated for and translated into a T-score per the PROMIS scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. A higher score represents worse symptomology for the Anxiety domain. The change from baseline in PROMIS Anxiety Score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change in Baseline in PROMIS - Depression T-Score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank version 2.0 - Depression T-Score will be used to assess trends over time in this health measure. The raw score is calculated for and translated into a T-score per the PROMIS scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. A higher score represents worse symptomology for the Depression domain. The change from baseline in PROMIS Depression Score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change in Baseline in PROMIS - Fatigue T-Score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank version 2.0 - Fatigue T-Score will be used to assess trends over time in this health measure. The raw score is calculated for and translated into a T-score per the PROMIS scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. A higher score represents worse symptomology for the Fatigue domain. The change from baseline in PROMIS Fatigue Score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change in Baseline in PROMIS - Sleep Disturbance T-Score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank version 2.0 - Sleep Disturbance T-Score will be used to assess trends over time in this health measure. The raw score is calculated for and translated into a T-score per the PROMIS scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. A higher score represents worse symptomology for the Sleep Disturbance domain. The change from baseline in PROMIS Sleep Disturbance Score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change in Baseline in PROMIS - Social Role Satisfaction T-Score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank version 2.0 - Social Role Satisfaction T-Score will be used to assess trends over time in this health measure. The raw score is calculated for and translated into a T-score per the PROMIS scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. A higher score better functioning for the Social Role Satisfaction domain. The change from baseline in PROMIS Social Role Satisfaction Score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change in Baseline in PROMIS - Pain Interference T-Score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank version 2.0 - Pain Interference T-Score will be used to assess trends over time in this health measure. The raw score is calculated for and translated into a T-score per the PROMIS scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. A higher score represents worse symptomology for the Pain Interference domain. The change from baseline in PROMIS Pain Interference Score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change in Baseline in PROMIS - Pain Intensity	The Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank version 2.0 - Pain Intensity will be used to assess trends over time in this health measure. The Pain Intensity on the PROMIS is a single item numerical rating scale where the respondent selects a whole number representing the average pain of the past 7 days ranging from 0 (no pain) to 10 (worst pain imaginable). The change from baseline in PROMIS Pain Intensity Score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Change in Baseline in PROMIS Cognitive Function T-Score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Item Bank version 2.0 - Cognitive Function scale will be used to assess trends over time in this health measure. The raw score is calculated for and translated into a T-score per the PROMIS scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. A higher score represents better cognitive function. The change from baseline in PROMIS Cognitive Function Score at Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85) will be assessed.	Visit 1 (Baseline, Day 1), Visit 3 (Day 29), Visit 4 (Day 57), and Visit 5 (Day 85 - Last Day of Treatment)
Percentage of Participants Indicating Clinical Benefit in Treatment Satisfaction	At the end of treatment, the participant and their physician will complete separately a survey asking what treatment assignment they believe they received (e.g., JBT-101, placebo, or cannot tell), whether the participant received benefit from their assigned treatment and whether the participant or their physician would choose the treatment received. The percentage of participants who responded that they received clinical benefit from the experimental drug treatment at the end of treatment will be assessed.	Visit 5 (Day 85 - Last Day of Treatment)
Percentage of Physicians Indicating Participant Clinical Benefit in Treatment Satisfaction	At the end of treatment, the participant and their physician will complete separately a survey asking what treatment assignment they believe they received (e.g., JBT-101, placebo, or cannot tell), whether the participant received benefit from their assigned treatment and whether the participant or their physician would choose the treatment received. The percentage of physicians who responded that the participant received clinical benefit from the experimental drug treatment at the end of treatment will be assessed.	Visit 5 (Day 85 - Last Day of Treatment)
Number of Grade 3 or Higher Treatment-emergent Adverse Events (TEAE) Related to Study Product	Treatment-emergent Adverse Events grading will be defined by the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. The number of TEAE will be identified by monitoring participant-reported AEs, vital signs, medical history, physical exams, blood and urine safety tests, 12-lead electrocardiograms, and the Addiction Research Center Inventory-Marijuana (ARCI-M). TEAE are defined as AEs that, in the opinion of the blinded/masked site investigator, are " possibly", "probably" or "definitely" related to the assigned study treatment.	Day 1 after initiation of study intervention through Day 113
Number of Treatment Emergent QTc Prolongation Events	The number of treatment emergent QTc prolongation events will be identified when QTc prolongation > 500 msec total duration and when the change from Visit 1 (Day 1) QTc interval prior to study drug administration > 60 msec Twelve-lead ECGs were recorded in triplicate at Screening and Visits 1 (Day 1) and 5 (Day 85). The ECGs were evaluated for medically significant abnormalities and QT/QTc intervals. The QT/QTc intervals were measured at Visit 1 (Day 1) before administration and between 2.5 and 3.5 hours after administration of study product in the clinic, at the time of maximum JBT-101 concentration in the blood.	Visit 1 (Baseline, Day 1) and Visit 5 (Day 85 - Last Day of Treatment)
Number of SLE Disease Flares by Severity Using the SELENA-SLEDAI Flare Index (SFI)	The number of mild/moderate and severe disease flares will be assessed using the SFI instrument to define disease flare(s) and severity. The SELENA SLEDAI Flare Index categorizes disease flares as mild/moderate or severe, based on the highest categories of clinical features recorded or by treatment recommendations by the physician.	Visit 3 (Day 29)
Number of SLE Disease Flares by Severity Using the SELENA-SLEDAI Flare Index (SFI)	The number of mild/moderate and severe disease flares will be assessed using the SFI instrument to define disease flare(s) and severity. The SELENA SLEDAI Flare Index categorizes disease flares as mild/moderate or severe, based on the highest categories of clinical features recorded or by treatment recommendations by the physician.	Visit 4 (Day 57)
Number of SLE Disease Flares by Severity Using the SELENA-SLEDAI Flare Index (SFI)	The number of mild/moderate and severe disease flares will be assessed using the SFI instrument to define disease flare(s) and severity. The SELENA SLEDAI Flare Index categorizes disease flares as mild/moderate or severe, based on the highest categories of clinical features recorded or by treatment recommendations by the physician.	Visit 5 (Day 85)
Number of SLE Disease Flares by Severity Using the SELENA-SLEDAI Flare Index (SFI)	The number of mild/moderate and severe disease flares will be assessed using the SFI instrument to define disease flare(s) and severity. The SELENA SLEDAI Flare Index categorizes disease flares as mild/moderate or severe, based on the highest categories of clinical features recorded or by treatment recommendations by the physician.	Visit 6 (Day 113)
Number of BILAG-2004 Disease Flares	The number of BILAG-2004 disease flares as defined as one new BILAG A or two new BILAG B scores will be assessed. The BILAG-2004* is a validated index for assessing SLE disease activity. The BILAG-2004 includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems. * BILAG-2004: British Isles Lupus Assessment Group 2004.	Visit 3 (Day 29)
Number of BILAG-2004 Disease Flares	The number of BILAG-2004 disease flares as defined as one new BILAG A or two new BILAG B scores will be assessed. The BILAG-2004* is a validated index for assessing SLE disease activity. The BILAG-2004 includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems. * BILAG-2004: British Isles Lupus Assessment Group 2004.	Visit 4 (Day 57)
Number of BILAG-2004 Disease Flares	The number of BILAG-2004 disease flares as defined as one new BILAG A or two new BILAG B scores will be assessed. The BILAG-2004* is a validated index for assessing SLE disease activity. The BILAG-2004 includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems. * BILAG-2004: British Isles Lupus Assessment Group 2004.	Visit 5 (Day 85)
Number of BILAG-2004 Disease Flares	The number of BILAG-2004 disease flares as defined as one new BILAG A or two new BILAG B scores will be assessed. The BILAG-2004* is a validated index for assessing SLE disease activity. The BILAG-2004 includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems. * BILAG-2004: British Isles Lupus Assessment Group 2004.	Visit 6 (Day 113)
Number of Treatment Emergent Events With Elevated Liver Tests	The number of participants with elevated liver tests, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 x upper limit of normal and total bilirubin > 1.5 x the upper limit of normal, present on repeat testing, at Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113) will be assessed.	Day 1 through Visit 6 (Day 113)
Number of Treatment Emergent Intolerability Events	The number of intolerability events of the study drug, defined as incidence of discontinuation of study product due to TEAEs at least possibly related to study product from Visits 1 (Day 1) through 5 (Day 85) will be assessed.	Day 1 after initiation of study intervention through Visit 5 (Day 85 - Last Day of Treatment)
Percentage of Participants With Increased Scores From Baseline on ARCI-M	The percentage of participants who experienced ≥1 score increase on the ARCI-M from the Visit 1 (Day 1) pre-dose assessment at Visit 1 (Day 1) post-dose, Visit 3 (Day 29) and Visit 5 (Day 85) will be assessed. The ARCI-M questionnaire was completed by subjects at Visit1 (Day 1) pre- and post-dosing, Visit 3 (Day 29) and Visit 5 (Day 85). This is a 12-item true/false questionnaire developed by the National Institutes of Drug Abuse, designed to detect the full range of subjective responses experienced by marijuana users. An answer of true has an assigned value of 1 and an answer of false has an assigned value of 0. The ARCI-M score was computed as the sum of the assigned values for all 12 questions and can range from 0 to 12. If a question is missed, the score is not calculated.	Visit 1 (Baseline, Day 1-prior to treatment initiation), Visit 1 (Baseline, Day 1-post-treatment initiation) Visit 3 (Day 29) and Visit 5 (Day 85 - Last Day of Treatment)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Rho Federal Systems Division, Inc.; Autoimmunity Centers of Excellence; Corbus Pharmaceuticals Inc.
• Investigators: Study Chair: Meggan Mackay, M.D., M.S., The Feinstein Institute for Medical Research; Study Chair: Robert B. Zurier, M.D., The Feinstein Institute for Medical Research

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website
• Autoimmunity Centers of Excellence (ACE) website
• Corbus Pharmaceuticals and Clinical Programs in Systemic Lupus Erythematosus

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2017
• Primary Completion (Actual): July 28, 2021
• Study Completion (Actual): July 28, 2021

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (Actual): March 28, 2017

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: randomized trial; efficacy; JBT-101 (also known as lenabasum); musculoskeletal disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; 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: DAIT ALE09; NIAID CRMS ID#: 30147 (Other Identifier: DAIT NIAID); UM1AI110494 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The plan is to share data in ImmPort [https://immport.niaid.nih.gov/ ], a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts, upon completion of the study.
• IPD Sharing Time Frame: After completion of the study.
• IPD Sharing Access Criteria: Data is available to the public once Individual Participant-Level data is posted to ImmPort.

Drug and device information, study documents

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