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Trial registered on ANZCTR


Registration number
ACTRN12620000712909
Ethics application status
Approved
Date submitted
29/05/2020
Date registered
30/06/2020
Date last updated
30/06/2020
Date data sharing statement initially provided
30/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study of the Pharmacokinetics and Safety of a Single Dose of Lenabasum in Subjects with Hepatic Impairment Compared with Matched Healthy Controls
Scientific title
A Phase 1, Single-dose, Non-Randomized, Open-label, Parallel-group Study to Assess the Pharmacokinetics and Safety of Lenabasum in Subjects with Hepatic Impairment Compared with Matched Healthy Controls
Secondary ID [1] 300957 0
Protocol Number: JBT101-HIS-001

Secondary ID [2] 301496 0
Regulatory Agency Identifying Number: US FDA IND No.: 116313
Universal Trial Number (UTN)
NA
Trial acronym
Linked study record
NA

Health condition
Health condition(s) or problem(s) studied:
Hepatic impairment 317677 0
Liver cirrhosis 317856 0
Condition category
Condition code
Oral and Gastrointestinal 315755 315755 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product: lenabasum (CB2 agonist)
Subjects with mild, moderate and severe hepatic impairment will be enrolled, along with matched healthy control subjects. All subjects will receive a single, oral capsule of lenabasum 20 mg. A hand and mouth check will be done after dose administration. The study will compare the PK of lenabasum in adults with mild, moderate and severe hepatic impairment to that in the matched controls.
Intervention code [1] 317713 0
Treatment: Drugs
Comparator / control treatment
There is no control treatment arm. All subjects will receive the same intervention.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323963 0
Plasma concentration-time profiles and pharmacokinetics of lenabasum in terms of Cmax and AUC
Timepoint [1] 323963 0
Up to 48 hours post-dose as specified below:
Day Time Point Relative to Dosing
Day 1 Predose
30 min postdose
1 h postdose
1.5 h postdose
2 h postdose
2.5 h postdose
3 h postdose
3.5 h postdose
4 h postdose
5 h postdose
6 h postdose
8 h postdose
12 h postdose
Day 2 24 h postdose
36 h postdose
Day 3 48 h postdose
Secondary outcome [1] 383444 0
Plasma PK parameters including but not limited to Tmax, t1/2, Vd/F, and CL/F.
Timepoint [1] 383444 0
Up to 48 hours post-dose as specified below:
Day Time Point Relative to Dosing
Day 1 Predose
30 min postdose
1 h postdose
1.5 h postdose
2 h postdose
2.5 h postdose
3 h postdose
3.5 h postdose
4 h postdose
5 h postdose
6 h postdose
8 h postdose
12 h postdose
Day 2 24 h postdose
36 h postdose
Day 3 48 h postdose

Secondary outcome [2] 383445 0
Urinary PK parameters: Ae, Fe, and CLR.
Timepoint [2] 383445 0
Up to 48 hours post-dose, pooled at the following collection intervals: 0- to 6-hour, 6- to 12-hour, 12- to 24-hour, and 24 to 48-hour postdose.
Secondary outcome [3] 383446 0
Nature, frequency, and severity of AEs/SAEs, including relationship to study treatment, AEs/SAEs leading to discontinuation of the study, and changes in laboratory parameters, vital signs, 12 lead ECG, and other safety assessments (specific for the management of AE’s, e.g. imaging if required).
Clinical laboratory safety assessments of both blood and urine include:
Hematology Full blood count with differential White Blood Cell Count with Differential:
Platelet Count Neutrophils
Red Blood Cell Count Lymphocytes
Hemoglobin Monocytes
Hematocrit Eosinophils
Red Blood Cell Indices: Basophils
Mean corpuscular volume
Mean corpuscular hemoglobin
Mean cell hemoglobin concentration
Reticulocyte count
Biochemistry
Creatinine Aspartate Aminotransferase/ Serum Glutamic-Oxaloacetic Transaminase
Glucose [nonfasting] Alanine Aminotransferase/ Serum Glutamic-Pyruvic Transaminase
HbA1c Alkaline phosphatase
Gamma glutamyl transferase Creatine kinase
Urea Chloride
Magnesium Amylase
Cholesterol Total and direct bilirubin
Potassium Total Protein
Sodium Phosphate Carbon dioxide (bicarbonate)
Calcium Potassium a-fetoprotein
Lactate dehydrogenase Thyroid stimulating hormone (Screening only)
Albumin Triglycerides
Uric acid
C-reactive protein
Coagulation
International normalized ratio Activated partial thromboplastin time
Thrombin clotting time Fibrinogen

Urinalysis
Leucocytes Red blood cells
Protein pH
Bilirubin Nitrite
Urobilinogen Specific gravity
Ketones Glucose
Microscopy (if clinically indicated) Urine creatinine
Timepoint [3] 383446 0
AEs will be collected throughout the study period from the time of informed consent.
Vitals signs (blood pressure, pulse rate, and body temperature) will be measured at Screening, Day -1, and at the following time points: On Day 1, predose (within 30 min prior to dosing), and 1 h, 4 h, 8 h, and 12 h postdose; Day 2 (24 h postdose); Day 3 (48 h postdose); and Day 8 (168 h postdose).
ECGs will be done at Screening, Day -1, and at the following time points: On Day 1, predose (within 30 min prior to dosing); Day 3 (48 h postdose); and Day 8 (168 h postdose).
Blood Samples for clinical lab safety assessments (hematology, biochemistry and coagulation) will be collected at Screening, Day -1, Day 2 (24 h postdose), Day 3 (48 h postdose) and Day 8 (168 h postdose).
Urine for urinalysis will be collected at Screening, Day -1, Day 2 (24 h postdose), Day 3 (48 h postdose) and Day 8 (168 h postdose).

Eligibility
Key inclusion criteria
• Male and female subjects aged greater than or equal to 18 years at Screening with suitable veins for cannulation or repeated venipuncture
• Healthy or have stable and well-controlled comorbidities

Subjects with Hepatic Impairment must:
o have stable chronic hepatic impairment with liver cirrhosis for at least 3 months
o meet the impairment criteria for the group they are enrolled (mild equals Child-Pugh Class A, moderate equals Child-Pugh Class B, or severe equals Child Pugh Class C) at screening
o meet all of the following laboratory parameters at Screening:
o Alanine aminotransferase less than or equal to 10 × ULN
o Bilirubin less than or equal to 100 µmol/L
o International normalized ratio <2.5
o Absolute neutrophil count greater than or equal to 1.0 × 109/L
o Platelet counts greater than or equal to 30 × 109/L
o Hemoglobin greater than or equal to 90 g/L
o a-fetoprotein less than or equal to 50 µg/L
o Glycated hemoglobin A1c <9% or equivalent (eg, <75 mmol/mol).

Control subjects should be matched to a subject with hepatic impairment in terms of:
o age (±10 years)
o body weight (±20%)
o sex
o race (if possible)

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• History of diseases or surgeries of the gastrointestinal tract.
• Have had cancer in the last three years (some treated skin cancers are permitted).
• Have a current infection, or infections that keep coming back despite treatment
• History of any other medical, psychiatric, or substance abuse condition, concurrent medical therapies, or abnormal laboratory values that in the opinion of the Investigator may put the subject at greater safety risk, influence response to study drug, or interfere with study assessments.
• Known hypersensitivity to lenabasum or any of its excipients.
• Have an estimated creatinine clearance <50 mL/min at Screening using the Cockcroft Gault formula.
• Have uncontrolled hypertension
• Are a regular user of nicotine products (e.g. smoke more than 10 cigarettes per day).
• Have an average alcohol intake of more than 10 drinks per week (women) or 15 drinks / week (men). One drink equals 360 mL beer, 150 mL wine, or 45 mL spirits.
• Use of medications which are known strong cytochrome P450 isoenzyme substrates/inducers/inhibitors within 30 days prior to study dosing and for the duration of the study.
• Participation in any other clinical study
Additional criterion apply for subjects with hepatic impairment, including but not limited to:
• Presence of severe hepatic encephalopathy of Grade 3 or 4
• Presence of acute liver disease
• History of liver transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
NA
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All 4 groups of varying hepatic impairment will be administered a single dose of oral lenabasum 20 mg on Day 1
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
Sample Size: No formal sample size calculation has been performed for this study. The sample size of 8 subjects to obtain approximately 6 evaluable subjects per hepatic function group is chosen based on feasibility, FDA guidance, and clinical judgment to provide adequate precision in describing the effect of hepatic impairment on lenabasum PK.
Statistical Analysis: To assess the effect of hepatic impairment on the plasma PK of lenabasum, log-transformed Cmax and AUC will be separately analyzed using a linear fixed-effect analysis of variance model with hepatic function group as a fixed-effect. Transformed back from the logarithmic scale, geometric least-squares means together with the associated 2-sided 95% confidence intervals (CIs) for Cmax and AUC will be estimated and presented. Also, ratios of geometric least-squares means (hepatic impairment group versus matched control group) together with 2-sided 90% CIs will be estimated and presented. In addition, the relationships between log-transformed plasma PK parameters (eg, Cmax, AUC, CL/F, and Vd/F) for lenabasum measures of hepatic impairment (ie, Child-Pugh score and/or each of its components) will be assessed using a regression model across hepatic function groups.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22587 0
New Zealand
State/province [1] 22587 0
Auckland and Christchurch

Funding & Sponsors
Funding source category [1] 305403 0
Commercial sector/Industry
Name [1] 305403 0
Corbus Pharmaceuticals
Address [1] 305403 0
500 River Ridge Dr
Norwood, MA
02062
USA
Country [1] 305403 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Corbus Pharmaceuticals Inc
Address
500 River Ridge Dr
Norwood, MA
02062
USA
Country
United States of America
Secondary sponsor category [1] 305786 0
Commercial sector/Industry
Name [1] 305786 0
IQVIA RDS Pty Ltd
Address [1] 305786 0
Unit A, 2 Rothwell Avenue
Rosedale
Auckland 0632
New Zealand
Country [1] 305786 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305725 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 305725 0
Ministry of Health
PO Box 5013
Wellington 6140

Ethics committee country [1] 305725 0
New Zealand
Date submitted for ethics approval [1] 305725 0
16/04/2020
Approval date [1] 305725 0
09/06/2020
Ethics approval number [1] 305725 0
20/NTB/91

Summary
Brief summary
This Phase 1 study aims to evaluate, characterize, and compare the PK and short-term safety profile of single-dose orally administered lenabasum in subjects with varying degrees of hepatic impairment and in matched healthy control subjects with normal hepatic function. The data generated from this study may allow subjects with a broader range of hepatic function to enter future studies and eventually receive this medication should it be approved for use by regulatory authorities.
Trial website
NA
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101366 0
Dr Edward Gane
Address 101366 0
Auckland Clinical Studies,
PO Box 8963, Symonds Street,
Auckland 1150
Country 101366 0
New Zealand
Phone 101366 0
+64 93733474
Fax 101366 0
+64 93733479
Email 101366 0
EdGane@adhb.govt.nz
Contact person for public queries
Name 101367 0
Ms Margaret Joppa
Address 101367 0
Auckland Clinical Studies,
PO Box 8963, Symonds Street,
Auckland 1150
Country 101367 0
New Zealand
Phone 101367 0
+64 93733474
Fax 101367 0
+64 93733479
Email 101367 0
Jasper@clinicalstudies.co.nz
Contact person for scientific queries
Name 101368 0
Dr Michael Tillinger, MD
Address 101368 0
Corbus Pharmaceuticals
500 River Ridge Dr.
Norwood, MA 02062
Country 101368 0
United States of America
Phone 101368 0
+1 7816008306
Fax 101368 0
Email 101368 0
Michael.Tillinger@corbuspharma.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We do not plan to make individual subject data publicly available.
Deidentified Individual subject data is to be used in support of NDA filing and therefore, would compromise business needs if required to make available prior to Marketing Authorization Approval.
What supporting documents are/will be available?
No other documents available
Summary results
No Results