Clinical Trials Register

Summary
EudraCT Number:	2017-000372-29
Sponsor's Protocol Code Number:	JBT101-SSc-002
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-07-02
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2017-000372-29

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study of safety and efficacy of lenabasum in Systemic Sclerosis

A.3.2

Name or abbreviated title of the trial where available

A Phase 3 safety and efficacy study of Lenabasum in Systemic Sclerosis

A.4.1

Sponsor's protocol code number

JBT101-SSc-002

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Corbus Pharmaceuticals Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Corbus Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	TMC Pharma Services Ltd
B.5.2	Functional name of contact point	Regulatory Services
B.5.3	Address:
B.5.3.1	Street Address	Lodge Farm Barn, Elvetham Park Estate, Fleet Road
B.5.3.2	Town/ city	Hartley Wintney, Hampshire
B.5.3.3	Post code	RG27 8AS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441252842255
B.5.5	Fax number	+441252842277
B.5.6	E-mail	regulatory.services@tmcpharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/16/1808
D.3 Description of the IMP
D.3.1	Product name	Lenabasum
D.3.2	Product code	JBT-101
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LENABASUM
D.3.9.1	CAS number	137945-48-3
D.3.9.2	Current sponsor code	JBT-101
D.3.9.3	Other descriptive name	resunab, ajulemic acid, anabasum
D.3.9.4	EV Substance Code	SUB193005
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/16/1808
D.3 Description of the IMP
D.3.1	Product name	Lenabasum
D.3.2	Product code	JBT-101
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LENABASUM
D.3.9.1	CAS number	137945-48-3
D.3.9.2	Current sponsor code	JBT-101
D.3.9.3	Other descriptive name	resunab, ajulemic acid, anabasum
D.3.9.4	EV Substance Code	SUB193005
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Systemic Sclerosis (SSc)

E.1.1.1

Medical condition in easily understood language

A disease of the immune system attacking the connective tissue under the skin and around internal organs and blood vessels causing scarring and thickening of the tissue in these areas.

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10012977
E.1.2	Term	Diffuse systemic sclerosis
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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) at Week 52.

E.2.2

Secondary objectives of the trial

1. To evaluate the efficacy of lenabasum compared to placebo in the treatment of SSc by assessing change from Baseline in the modified Rodnan skin score (mRSS) at Week 52.
2. 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.
3. To evaluate the efficacy of lenabasum compared to placebo in the treatment of SSc by assessing the change from Baseline in the forced vital capacity (FVC) % score predicted at Week 52.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Part A:
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. Stable treatment for SSc ≥ 28 days before Visit 1.
8. 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.
9. Willing not to use any cannabinoids including recreational marijuana, medical marijuana and other prescription cannabinoids from Screening through Visit 11.
10. Women of childbearing potential must not be pregnant or breastfeeding at Screening or 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.
11. Male participants must be willing to follow contraceptive requirements and should not get anyone pregnant while they are taking the study product or within 28 days after taking the last dose of the study product, during which time period they or their partner must be willing to use at least one highly effective method of contraception.
12. Able to adhere to the study visit schedule and other protocol requirements.
Part B:
13. Complete dosing in Part A without permanent discontinuation of
study product for safety or tolerability reasons or voluntary withdrawal
from the study.
14. Complete Visit 11 of Part A.
15. Understand and voluntarily sign the informed consent.
16. Able to adhere to the study visit schedule and other protocol
requirements.

E.4

Principal exclusion criteria

Part A:
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 (topical corticosteroids are 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. Concomitant inflammatory myositis, rheumatoid arthritis or systemic lupus erythematosus when definite classification criteria for those diseases are met - Bohan and Peter criteria for polymyositis and dermatomyositis 1975);[Bohan and Peter, 1975a; Bohan and Peter, 1975b];; 2010 rheumatoid arthritis classification criteria of American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) (Aletaha, 2010); ACR revised criteria for the classification of systemic lupus erythematosus (Hochberg, 1997)].
4. SSc-like illnesses related to exposures or ingestions.
5. A positive test for anti-centromere antibody at Screening. If the subject is anti-centromere antibody positive and clearly has diffuse cutaneous SSc (see inclusion criteria #2), then the subject may be eligible and the investigator must discuss this situation with the Medical Monitor to determine eligibility.
6. 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 or treatment for gastrointestinal bacterial overgrowth.
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.
7. 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 g/dL in females.
c. Neutrophils < 1.0 × 1000,000,000/L.
d. Platelets < 75 × 1000,000,000/L.
e. Creatinine clearance in blood < 50 mL/min per the Modification of Diet in Renal Disease (MDRD) Study equation. Creatinine clearance may be assessed in a 24 hour urine collection to confirm eligibility (creatinine clearance ≥ 50 ml/min) if screening blood test is < 50 mL/min.
f. Aspartate aminotransferase or alanine aminotransferase > 2.0 × upper limit of normal.
8. Any investigational agent within 30 days or 5 therapeutic half-lives of that agent whichever is longer, before Visit 1.
9. Prior exposure to lenabasum.
10. 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.
Part B:
11. Patient should be excluded if cause of skin thickening or other features attributed to dSSc are now thought to be part of a different disease/diagnosis.
12. Any non-SSc disease or condition, including laboratory or other test abnormalities, or non-compliance, that has arisen during Part A that would preclude the safe administration of lenabasum in Part B, in the opinion of the investigator and/or Sponsor.

E.5 End points

E.5.1

Primary end point(s)

- Efficacy: American College of Rheumatology (ACR) Provisional Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score (lenabasum 20 mg BID)
- Safety: Treatment Emergent Adverse Events (TEAE) from Day 1

E.5.1.1

Timepoint(s) of evaluation of this end point

at Week 52

E.5.2

Secondary end point(s)

Efficacy:
- modified Rodnan skin score (mRSS) (lenabasum 20 mg BID and 5 mg
BID)
- Health Assessment Questionnaire-Disability Index (HAQ-DI) score (lenabasum 20 mg BID and 5 mg BID)
- Forced Vital Capacity (FVC) % predicted (lenabasum 20 mg BID and 5 mg BID)
- American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score (lenabasum 5 mg BID)
Safety:
- Tolerability (percentage of subjects discontinuing study product due to a TEAE probably or definitely related to study product) of lenabasum treatment or placebo treatment
- Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate, body temperature, and weight) recorded at each visit (Part A and Part B)
- Laboratory safety tests obtained at each visit (Part A) and Week 1, Week 4, Week 20, Week 36, Week 52, Week 68, Week 84, and Week 100
(Part B)
- Complete blood count (CBC) 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 (Part A) and
each visit (Part B)
- 12-lead ECGs: Day 1, Week 26, and Week 52 (Part A); Week 12, Week 44, Week 76, and Week 108 (Part B).
- Late emerging AEs (2-year safety follow-up)

E.5.2.1

Timepoint(s) of evaluation of this end point

Part A: at Week 52
Part B: at Week 108

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Part B: continuing open label for 2 yrs; 2yr safety follow-up for subjects

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Austria

Canada

Czech Republic

France

Germany

Israel

Italy

Japan

Korea, Republic of

Netherlands

Poland

Portugal

Spain

Sweden

Switzerland

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

140

F.4.2.2

In the whole clinical trial

354

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the trial, subjects will continue to receive care for systemic sclerosis from their treating physician. Subjects will remain on their baseline treatment for systemic sclerosis during the trial to reduce the risk of disease flare where study product is discontinued. It is the intent of the Sponsor to offer participation in a separate open-label extension (OLE)trial (Part B) with lenabasum for subjects who complete this trial (Part A) through to visit 11 (Day 365/Week 52).

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-09-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-12-21

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