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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03869697




Registration number
NCT03869697
Ethics application status
Date submitted
1/03/2019
Date registered
11/03/2019
Date last updated
2/02/2022

Titles & IDs
Public title
Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Malignant Pleural Effusions
Scientific title
A Phase I Study Evaluating the Safety, Tolerability, Efficacy, and Pharmacokinetics of SCB-313, a Fully-Human TRAIL-Trimer Fusion Protein, for the Treatment of Malignant Pleural Effusions
Secondary ID [1] 0 0
CLO-SCB-313-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Pleural Effusions 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SCB-313

Experimental: SCB-313 - Cohorts in SAD phase: 5 mg, 10mg, 20mg, 40mg, 80 mg. Cohort in MAD phase: biological effective dose determined from SAD phase. 1 intrapleural injection of SCB-313 on Day 1 for the SAD cohorts, and 3 intrapleural injections of SCB-313 on Days 1, 2 and 3 for the MAD cohort.


Treatment: Drugs: SCB-313
5 mg or 20 mg lyophilized powder in a single-use glass vial
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of DLT
Timepoint [1] 0 0
Up to 21 days after start of treatment
Secondary outcome [1] 0 0
SAEs or TEAEs
Timepoint [1] 0 0
Up to 21 days after start of treatment
Secondary outcome [2] 0 0
Immunogenicity
Timepoint [2] 0 0
Up to 21 days after start of treatment
Secondary outcome [3] 0 0
Pleural effusion response rate at Day 21
Timepoint [3] 0 0
At Day 21 after start of treatment
Secondary outcome [4] 0 0
Pleural effusion drainage-free rate at Day 21
Timepoint [4] 0 0
At Day 21 after start of treatment
Secondary outcome [5] 0 0
The changes in effusion volume and flow rate after SCB-313 treatment , and at next drainage over the baseline daily effusion flow rate.
Timepoint [5] 0 0
Up to 6 months after start of treatment
Secondary outcome [6] 0 0
Blood oxygen levels
Timepoint [6] 0 0
Up to 21 days after start of treatment
Secondary outcome [7] 0 0
Overall survival
Timepoint [7] 0 0
Up to 6 months after start of treatment
Secondary outcome [8] 0 0
Pharmacokinetics (Cmax)
Timepoint [8] 0 0
Up to 4 days after start of treatment
Secondary outcome [9] 0 0
Pharmacokinetics(Cmax/D)
Timepoint [9] 0 0
Up to 4 days after start of treatment
Secondary outcome [10] 0 0
Pharmacokinetics(Tmax)
Timepoint [10] 0 0
Up to 4 days after start of treatment
Secondary outcome [11] 0 0
Pharmacokinetics ([AUC]0-24)
Timepoint [11] 0 0
Up to 4 days after start of treatment
Secondary outcome [12] 0 0
Pharmacokinetics (AUC0-24/D)
Timepoint [12] 0 0
Up to 4 days after start of treatment
Secondary outcome [13] 0 0
Pharmacokinetics ((AUC0-last))
Timepoint [13] 0 0
Up to 4 days after start of treatment
Secondary outcome [14] 0 0
Pharmacokinetics (Ctrough)
Timepoint [14] 0 0
Up to 4 days after start of treatment
Secondary outcome [15] 0 0
Amount of drug in pleural effusion
Timepoint [15] 0 0
Up to 4 days after start of treatment
Secondary outcome [16] 0 0
Pharmacokinetics (AUC 0-inf)
Timepoint [16] 0 0
Up to 4 days after start of treatment
Secondary outcome [17] 0 0
Pharmacokinetics (AUC0-inf/D)
Timepoint [17] 0 0
Up to 4 days after start of treatment
Secondary outcome [18] 0 0
Pharmacokinetics (t1/2)
Timepoint [18] 0 0
Up to 4 days after start of treatment
Secondary outcome [19] 0 0
Pharmacokinetics (CL/F serum only)
Timepoint [19] 0 0
Up to 4 days after start of treatment
Secondary outcome [20] 0 0
Pharmacokinetics (Vz/F serum only)
Timepoint [20] 0 0
Up to 4 days after start of treatment
Secondary outcome [21] 0 0
Pharmacokinetics (?z)
Timepoint [21] 0 0
Up to 4 days after start of treatment
Secondary outcome [22] 0 0
Tumor response
Timepoint [22] 0 0
Up to 6 months after start of treatment
Secondary outcome [23] 0 0
Carcinoembryonic antigen (CEA)
Timepoint [23] 0 0
Up to 21 days after start of treatment
Secondary outcome [24] 0 0
CA-125
Timepoint [24] 0 0
Up to 21 days after start of treatment
Secondary outcome [25] 0 0
CA-19-9
Timepoint [25] 0 0
Up to 21 days after start of treatment
Secondary outcome [26] 0 0
Changes in 24-hour urine volume
Timepoint [26] 0 0
Up to 4 days after start of treatment
Secondary outcome [27] 0 0
Changes in GFR
Timepoint [27] 0 0
Up to 4 days after start of treatment
Secondary outcome [28] 0 0
Changes in tumor cell count in pleural effusion samples
Timepoint [28] 0 0
Up to 4 days after start of treatment
Secondary outcome [29] 0 0
Caspase-cleaved CK18
Timepoint [29] 0 0
Up to 10 days after start of treatment
Secondary outcome [30] 0 0
KRAS mutation
Timepoint [30] 0 0
Baseline
Secondary outcome [31] 0 0
MMR defects
Timepoint [31] 0 0
Baseline
Secondary outcome [32] 0 0
Bcl2 overexpression
Timepoint [32] 0 0
Baseline
Secondary outcome [33] 0 0
TRAIL resistance
Timepoint [33] 0 0
Baseline

Eligibility
Key inclusion criteria
1. Histologically or cytologically confirmed cancer of any primary tumor type.
2. Malignant pleural effusion causing respiratory symptoms requiring drainage that is histologically or cytologically confirmed; or pleural effusion with radiologically proven pleural malignancy as diagnosed in normal clinical practice on thoracic computed tomography in the absence of histocytological or cytological proof.
3. Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2. Patients with an ECOG performance status of 3 may be included if the Investigator determines that removal of pleural fluid would improve their performance status to 2 or better.
4. Life expectancy of at least 8 weeks.
5. Age =18 years.
6. Adequate hematologic function, defined as:

1. Platelet count =75,000/µL;
2. Prothrombin time and activated partial thromboplastin time =1.5 times the upper limit of normal (ULN);
3. Absolute neutrophil count =1,500 µL;
4. Hemoglobin =8 g/dL (transfusion and erythropoietic agents are allowed). In case there is existence of active bleeding or other persistent condition of either increased destruction or impaired production of erythrocytes, which may require repeated transfusion or erythropoietic treatment, the eligibility must be discussed with the Sponsor on a case-by-case basis prior to randomization).
7. Adequate renal function, defined as creatinine clearance >40 mL/minute.
8. Adequate liver function, defined as:

1. Aspartate aminotransferase and alanine aminotransferase =2.0 times ULN;
2. Bilirubin =2.0 times ULN, unless patient has known Gilbert's syndrome.
9. Female patients of childbearing potential (excluding women who have undergone surgical sterilization or are menopausal, defined as no menstrual periods for 1 year or more without any other medical reasons) are eligible if they have negative serum pregnancy test result 7 days before the first dose of SCB-313 and are willing to use an effective method of birth control/contraception to prevent pregnancy until 6 months after discontinuation of SCB-313.

Both men and women of reproductive potential must agree to use effective contraception during the study and for 6 months after discontinuation of SCB-313.

Note: Contraceptive methods that are considered highly effective areas follows: total abstinence, intrauterine device, double barrier method (such as condom plus diaphragm with spermicide), contraceptive implant, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release), or vasectomized partner with confirmed azoospermia.
10. Willing to attend follow-up visits on Days 10, and 21 after the first study drug administration.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Significantly loculated pleural effusions not amenable to drainage or patient is unlikely to benefit from intrapleural therapy.
2. Concurrent use of any investigational product (IP) or investigational medicine within 28 days before Day 1 of study drug administration.
3. Radiotherapy outside the chest field within 2 weeks, or radical radiotherapy to pleural or lung lesions within 8 weeks prior to enrollment (Note: palliative radiotherapy to the chest is allowed).
4. Start a new systemic anticancer therapy, including chemotherapy, targeted therapy, immuno-oncology (I-O) therapy regimen, within 28 days before Day 1 of study drug administration or during DLT observation period.
5. Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous antibiotics within 2 weeks prior to enrollment.
6. Clinical unstable or uncontrolled concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
7. History of gross hemoptysis (>2.5 mL).
8. Residual adverse events (AEs) > Grade 2 from previous treatment.
9. Evidence or suspicion of relevant psychiatric impairment, including alcohol or recreational drug abuse.
10. Myocardial infarction within 6 months prior to treatment and/or prior diagnoses of congestive heart failure (New York Heart Association Class III or IV), unstable angina, unstable cardiac arrhythmia requiring medication, and/or long QT syndrome or QT/QTc interval >480 msec at Baseline.
11. Uncontrolled hypertension defined as systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg confirmed upon repeated measures (note: no more than 3 repeated measures allowed).
12. Major surgery (open procedures) within 4 weeks prior to enrollment.
13. Patient with ileus within 30 days prior to Screening.
14. Positive serology test for human immunodeficiency virus type 1 and/or 2, or known history of other immunodeficiency disease.
15. Live vaccine within 2 weeks prior to enrollment.
16. Scheduled participation in another clinical study involving an investigational product or device during the DLT observation period of this study.
17. Previous treatment with a TRAIL-based therapy or death receptor 4/5 agonist therapy.
18. Known or suspected hypersensitivity to any component of SCB-313.
19. Any further condition which, in the opinion of the Investigator, may result in undue risk of the patient by participating in the present study.
20. Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/11/2021
Sample size
Target
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Orange Health Service - Orange
Recruitment hospital [3] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [4] 0 0
SCGH (Sir Charles Gairdner Hospital) - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2800 - Orange
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Clover Biopharmaceuticals AUS Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety, tolerability, preliminary efficacy, and PK/PD of SCB-313 (recombinant human TRAIL-Trimer fusion protein) administered once via intrapleural injection (SAD) and once daily over 2 to 3 days (MAD)for the treatment of cancer patients with symptomatic malignant pleural effusions requiring drainage.
Trial website
https://clinicaltrials.gov/study/NCT03869697
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03869697