A study of safety and efficacy of lenabasum in Systemic Sclerosis

• Register: EUCTR
• Last refreshed on: 12 April 2021
• Main ID: EUCTR2017-000372-29-ES
• Date of registration: 02/02/2018
• Prospective Registration: Yes
• Primary sponsor: Corbus pharmaceuticals Inc.
• Public title: A study of safety and efficacy of lenabasum in Systemic Sclerosis
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate Efficacy and Safety of Lenabasum in Diffuse Cutaneous Systemic Sclerosis - A Phase 3 safety and efficacy study of Lenabasum in Systemic Sclerosis
• Date of first enrolment: 25/04/2018
• Target sample size: 354
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000372-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Regulatory Services
• Affiliation: TMC Pharma Services Ltd

• Name: Regulatory Services
• Affiliation: TMC Pharma Services Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Fulfills the 2013 American College of Rheumatology criteria for systemic sclerosis (van den Hoogen et al, 2013).
2. Diffuse cutaneous SSc (skin thickening on upper arms proximal to the elbows, upper legs proximal to the knees, or trunk).
3. = 18 years of age at the time Informed Consent is signed.
4. Written informed consent from the subject.
5. Disease duration = 6 years from the first non-Raynaud’s symptom. If disease duration is > 3 years and = 6 years, then mRSS = 15. Subjects with disease duration > 3 years and = 6 years and mRSS = 15 will be limited to no more than 1/3rd of the subjects.
6. Patient Global Assessment = 3 or MDGA = 3.
7. Overlap with polymyositis, systemic lupus erythematosus, Sjogren’s syndrome, or rheumatoid arthritis is allowed only if the dominant clinical disease is diffuse cutaneous SSc.
8. Stable treatment for SSc = 28 days before Visit 1.
9. Willing to not start or stop any immunosuppressive medications for SSc from Visit 1 through Visit 11, unless a change is considered in the subject’s best medical interest by the site investigator or another physician who has primary responsibility for treating the subject’s SSc.
10. Willing not to use any cannabinoids including recreational marijuana, medical marijuana and other prescription cannabinoids from Screening through Visit 11.
11. Women of childbearing potential must not be pregnant or breastfeeding at Visit 1 and must be using at least one highly effective method of contraception (failure rate < 1% per year) for
at least 28 days before Visit 1 and be willing to continue to use at least one highly effective method of contraception throughout the study and for at least 28 days after discontinuation of study product.
12. Male participants must be willing to follow contraceptive requirements and should not get anyone pregnant while they are taking the study drug or within 28 days after taking the last dose of the study drug, during which time period they or their partner must be willing to use at least one highly effective method of contraception.
13. Able to adhere to the study visit schedule and other protocol requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 329
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
1. Unstable SSc or SSc with end-stage organ involvement at Screening or Visit 1, such as:
a. On an organ transplantation list or has received an organ transplant
b. Renal crisis within 1 year
c. Interstitial lung disease requiring constant oxygen treatment. This excludes oxygen used to aid sleep or exercise.
d. Pulmonary hypertension requiring constant oxygen treatment. This excludes oxygen used to aid sleep or exercise.
e. Gastrointestinal dysmotility requiring total parenteral nutrition or hospitalization within 6 months before Visit 1.
2. Certain medications at Screening or Visit 1, including:
a. Treatment with any oral prednisone > 10 mg per day or equivalent within 28 days before Visit 1. Treatment with intravenous corticosteroids within 28 days before Visit 1 is not allowed, and treatment with intra-articular corticosteroids within 28 days before Visit 1 is allowed.
b. New or increase in doses of any non-corticosteroid immunosuppressive medication within 8 weeks before Screening.
c. Treatment with cyclophosphamide within 3 months before Visit 1.
3. Patients with SSc-like illnesses related to exposures or ingestions.
4. Significant diseases or conditions other than SSc that may influence response to the study product or safety, such as:
a. A new bacterial or viral infection that was treated with oral or intravenous antibiotics or anti-viral treatments within 28 days before Visit 1. This does not include prophylactic antibiotic or anti-viral treatments.
b. Acute or chronic hepatitis B or C infection.
c. Human immunodeficiency virus (HIV) infection.
d. History of active tuberculosis or positive tuberculosis test without a completed course of appropriate treatment or already completed at least 1 month of ongoing appropriate treatment.
e. Evidence of required treatment for cancer (except for treated basal or squamous cell carcinoma of the skin or cervical carcinoma in situ) within 3 years of Visit 1.
5. Any of the following values for laboratory tests at Screening:
a. A positive pregnancy test in WOCBP (also at Visit 1).
b. Hemoglobin < 9 g/dL in males and < 8 gm/dL in females.
c. Neutrophils < 1.0 × 1000000000/L.
d. Platelets < 75 × 1000000000/L.
e. Creatinine clearance < 50 mL/min per the Modification of Diet in Renal Disease (MDRD) Study equation.
f. Aspartate aminotransferase or alanine aminotransferase > 2.0 × upper limit of normal.
6. Any investigational agent within 30 days or 5 therapeutic half-lives of that agent whichever is longer, before Visit 1.
7. Significant diseases or conditions other than SSc 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic Sclerosis (SSc)
MedDRA version: 20.0 Level: LLT Classification code 10012977 Term: Diffuse systemic sclerosis System Organ Class: 100000004859

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Name: Lenabasum 5 mg Powder in Capsule
Product Code: JBT-101
Pharmaceutical Form: Capsule
INN or Proposed INN: Lenabasum
CAS Number: 137945-48-3
Current Sponsor code: JBT-101
Other descriptive name: resunab, ajulemic acid, anabasum
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-20
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Lenabasum 20 mg Powder in Capsule
Product Code: JBT-101
Pharmaceutical Form: Capsule
INN or Proposed INN: Lenabasum
CAS Number: 137945-48-3
Current Sponsor code: JBT-101
Other descriptive name: resunab, ajulemic acid, anabasum
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-20
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1. To evaluate the efficacy of lenabasum compared to placebo in the treatment of SSc by assessing the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score at Week 52.
2. To evaluate the efficacy of lenabasum compared to placebo in the treatment of SSc by assessing the American College of Rheumatology (ACR) Provisional Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score at Week 52.
3. To evaluate the efficacy of lenabasum compared to placebo in the treatment of SSc by assessing the change from baseline in the forced vitality capacity (FVC) % score at Week 52.

Main Objective: To evaluate the efficacy of lenabasum compared to placebo in the treatment of diffuse cutaneous systemic sclerosis (SSc) by assessing change from baseline in the modified Rodnan skin score (mRSS) at Week 52

Timepoint(s) of evaluation of this end point: at Week 52

Primary end point(s): - Efficacy: Modified Rodnan Skin Score (mRSS) (lenabasum 20 mg BID)
- Safety: Treatment Emergent Adverse Events (TEAE) from Day 1

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at Week 52

Secondary end point(s): Efficacy:
- Health Assessment Questionanaire-Disability Index (HAQ-DI) score (lenabasum 20 mg BID and 5 mg BID)
- American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score (lenabasum 20 mg BID and 5 mg BID)
- mRSS (lenabasum 5 mg BID)
- Forced Vital Capacity (FVC) % predicted (lenabasum 20 mg BID and 5 mg BID)
Safety:
- Tolerability (percentage of subjects discontinuing study treatment due to a TEAE probably or definitely related to study product) of lenabasum treatment and placebo treatment
- Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate, body temperature, and weight) recorded at each visit
- Laboratory safety tests obtained at each visit
- Complete blood count with cell differential and platelets
- Metabolic panel that includes renal function, electrolytes, and liver function tests
- Urine dipstick testing for blood, albumin/protein, and glucose
- Physical examinations at Day 1, Week 26, and Week 52
- 12-lead ECGs at Day 1, Week 26, and Week 52

Secondary ID(s)

JBT101-SSc-002

2017-000372-29-GB

Source(s) of Monetary Support

Corbus Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 11/04/2018
Contact: