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Trial registered on ANZCTR


Registration number
ACTRN12620000717954
Ethics application status
Approved
Date submitted
29/05/2020
Date registered
2/07/2020
Date last updated
21/10/2021
Date data sharing statement initially provided
2/07/2020
Date results information initially provided
21/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A 2-Part Study of the Pharmacokinetics and Safety of a Single Dose of Lenabasum in Subjects with Renal Impairment Compared with Matched Controls
Scientific title
A Phase 1, 2-part, Single-dose, Non-Randomized, Open-label, Parallel-group Study to Assess the Pharmacokinetics and Safety of Lenabasum in Subjects with Renal Impairment Compared with Matched Controls
Secondary ID [1] 301408 0
Protocol Number: JBT101-RIS-001
Secondary ID [2] 301511 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:
Renal impairment 317678 0
Renal insufficiency 317860 0
Condition category
Condition code
Renal and Urogenital 315757 315757 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product: lenabasum (CB2 agonist)
Subjects with mild, moderate and severe renal impairment will be enrolled, along with matched control subjects. All subjects will receive a single, oral capsule dose 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 renal impairment to that in the matched controls. Matched controls will be subjects with age-appropriate renal function. This group may include both subjects with FDA-defined normal renal function (GFR greater than 90) and subjects with physiologically age-appropriate decline in renal function (GRF 60-90) who are relatively healthy.
Intervention code [1] 317716 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] 323964 0
Plasma concentration-time profiles and pharmacokinetics of lenabasum in terms of Cmax and AUC
Timepoint [1] 323964 0
Up to 48 hours post-dose as specified below:
Day and 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] 383447 0
Plasma PK parameters including but not limited to Tmax, t1/2, Vd/F, and CL/F.
Timepoint [1] 383447 0
Up to 48 hours post-dose as specified below:
Day and 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] 383448 0
Urinary PK parameters: Ae, Fe, and CLR.
Timepoint [2] 383448 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] 383449 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.
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] 383449 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, pre dose (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, pre dose (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 greather than or equal to 18 years at Screening with suitable veins for cannulation or repeated venipuncture
• Subjects must meet the respective estimated creatinine clearance (mL/min) criteria for renal impairment:
o Severe: less than 30
o Moderate:30- 59
o Mild: 60-89
o Matched: greater than or equal to 60 (Matched controls will be subjects with age-appropriate renal function. This group may include both subjects with FDA-defined normal renal function (GFR greater than 90) and subjects with physiologically age-appropriate decline in renal function (GRF 60-90) who are relatively healthy)
• Stable renal function over the preceding 3-6 months
• Stable and well-controlled comorbidities

Matched subjects should be in the range of:
o age (±10 years)
o body weight (±20%)
o sex
o race (if possible)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Subjects with acute renal disease and/or history of renal transplant.
• Have had a kidney transplant, or are on dialysis.
• 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
• Have a history of alcohol or drug abuse / addiction (including cannabis) in the last five years.
• Are a regular user of nicotine products (e.g. you 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.
• Have uncontrolled hypertension
• 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.
• Known hypersensitivity to lenabasum or any of its excipients.
• Participation in any other clinical study

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All 4 groups of varying renal impairment will be administered a single dose of oral lenabasum 20 mg on Day 1.
Considering degree of renal impairment, the study will have mild, moderate and severe renal impairment patients. Matched controls will be subjects with age-appropriate renal function. This group may include both subjects with FDA-defined normal renal function (GFR greater than 90) and subjects with physiologically age-appropriate decline in renal function (GFR 60-90) who are relatively healthy.
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 approximately 8 subjects to obtain approximately 6 evaluable subjects per renal function group is chosen based on feasibility, FDA guidance, and clinical judgment to provide adequate precision in describing the effect of renal impairment on lenabasum PK.

Statistical Analysis: To assess the effect of renal 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 renal 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 (renal impairment group versus matched control group) together with 2-sided 90% CI will be estimated and presented. In addition, the relationship between log-transformed plasma PK parameters (Cmax and AUC) for lenabasum and estimated renal function (CrCl using the Cockcroft-Gault formula) will be assessed using a regression model across renal function groups.
The analyses will be repeated using eGFR calculated using the MDRD formula (per FDA guidance).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/07/2020
Actual
22/07/2020
Date of last participant enrolment
Anticipated
3/11/2020
Actual
29/11/2020
Date of last data collection
Anticipated
8/12/2020
Actual
29/11/2020
Sample size
Target
32
Accrual to date
Final
16
Recruitment outside Australia
Country [1] 22588 0
New Zealand
State/province [1] 22588 0
Christchurch and Auckland

Funding & Sponsors
Funding source category [1] 305845 0
Commercial sector/Industry
Name [1] 305845 0
Corbus Pharmaceuticals
Country [1] 305845 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] 306292 0
Commercial sector/Industry
Name [1] 306292 0
IQVIA RDS Pty Ltd
Address [1] 306292 0
Unit A, 2 Rothwell Avenue
Rosedale
Auckland 0632
New Zealand
Country [1] 306292 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306110 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 306110 0
Ministry of Health
PO Box 5013
Wellington 6140
Ethics committee country [1] 306110 0
New Zealand
Date submitted for ethics approval [1] 306110 0
16/04/2020
Approval date [1] 306110 0
05/06/2020
Ethics approval number [1] 306110 0
20/STH/62

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 renal impairment and in matched control subjects with age-appropriate renal function. The data generated from this study may allow subjects with a broader range of renal 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
NA
Public notes
NA

Contacts
Principal investigator
Name 102742 0
Dr Richard Robson
Address 102742 0
Christchurch Clinical Studies Trust Ltd
Level 4, 264 Antigua Street,
Christchurch, 8011,
Country 102742 0
New Zealand
Phone 102742 0
+64 33729477
Fax 102742 0
+64 33729478
Email 102742 0
[email protected]
Contact person for public queries
Name 102743 0
Dr Richard Robson
Address 102743 0
Christchurch Clinical Studies Trust Ltd
Level 4, 264 Antigua Street,
Christchurch, 8011,
Country 102743 0
New Zealand
Phone 102743 0
+64 33729477
Fax 102743 0
+64 33729478
Email 102743 0
[email protected]
Contact person for scientific queries
Name 102744 0
Dr Michael Tillinger, MD
Address 102744 0
Corbus Pharmaceuticals
500 River Ridge Dr.
Norwood, MA 02062
Country 102744 0
United States of America
Phone 102744 0
+1 7816008306
Fax 102744 0
Email 102744 0
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.