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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03443674




Registration number
NCT03443674
Ethics application status
Date submitted
7/01/2018
Date registered
23/02/2018
Date last updated
5/02/2020

Titles & IDs
Public title
Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Peritoneal Malignancies
Scientific title
A Phase I Study Evaluating Safety, Tolerability, and Pharmacokinetics of SCB-313, a Fully-Human TRAIL-Trimer Fusion Protein, for the Treatment of Peritoneal Malignancies
Secondary ID [1] 0 0
CLO-SCB-313-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peritoneal Malignancies 0 0
Condition category
Condition code

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

Experimental: SCB-313 - Dose escalation cohorts——10mg, 20mg, 40mg, 80mg, 160mg. For each cohort: administered twice weekly (eg.. Monday and Thursday or Tuesday and Friday) for 2 weeks (Days 1, 4, 8, and 11) by IP bolus injection.


Treatment: Drugs: SCB-313
Lyophilized powder in a single-use vial

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and Tolerability: Occurrence of serious adverse events (SAEs) and/or TEAEs - Regardless of causality or relationship to SCB-313 graded using National Cancer Institute Common Terminology Criteria for Adverse Events Version.4.03 (NCI CTCAE v4.03).
Timepoint [1] 0 0
Up to 41 days after start of treatment
Secondary outcome [1] 0 0
Immunogenicity: Occurrence of binding and neutralizing anti-SCB-313 antibodies - Occurrence of binding and neutralizing anti-SCB-313 antibodies
Timepoint [1] 0 0
Up to 41 days after start of treatment
Secondary outcome [2] 0 0
Pharmacokinetics (Cmax) - Maximum serum concentration
Timepoint [2] 0 0
Up to 12 days after start of treatment
Secondary outcome [3] 0 0
Pharmacokinetics (Cmax/D) - Dose-normalized Cmax of SCB-313
Timepoint [3] 0 0
Up to 12 days after start of treatment
Secondary outcome [4] 0 0
Pharmacokinetics (tmax) - Time to Cmax of SCB-313
Timepoint [4] 0 0
Up to 12 days after start of treatment
Secondary outcome [5] 0 0
Pharmacokinetics ([AUC]0-24) - Area under SCB-313 concentration time curve from zero to 24 hours
Timepoint [5] 0 0
Up to 12 days after start of treatment
Secondary outcome [6] 0 0
Pharmacokinetics (AUC0-24/D) - Dose-normalized AUC0-24 of SCB-313
Timepoint [6] 0 0
Up to 12 days after start of treatment
Secondary outcome [7] 0 0
Pharmacokinetics ((AUC0-last)) - Area under curve from time 0 on Day 1 to the last quantifiable concentration time point
Timepoint [7] 0 0
Up to 12 days after start of treatment
Secondary outcome [8] 0 0
Pharmacokinetics (Ctrough) - Trough concentration of SCB-313 at each predose and at 24 hours after the last dose
Timepoint [8] 0 0
Up to 12 days after start of treatment

Eligibility
Key inclusion criteria
1. Histologically or cytologically confirmed peritoneal malignancies after failure or
refusal of all approved therapies, and no better option available in the
Investigator's opinion.

2. Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2 (Patients with
ECOG score of 3 might be allowed to enter this trial per Investigator's judgment)

3. Life expectancy of at least 8 weeks

4. Age =18 years

5. Body mass index =17.0 kg/m2

6. Adequate hematological 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 serum creatinine =2.0 times ULN and creatinine
clearance >45 mL/minute

8. Adequate liver function, defined as:

1. Aspartate aminotransferase and alanine aminotransferase =3 times ULN for patients
without liver metastases, or =5 times ULN in the presence of liver metastases

2. Bilirubin =1.5 times ULN, unless patient has known Gilbert's syndrome

9. Female patients of childbearing potential (excluding women who have undergone surgical
sterilization or menopause. Menopause is defined as the status where no menstrual
periods continue for 1 year or more without any other medical reasons), are eligible
if they have negative serum pregnancy testing within 7 days prior to first dosing and
are willing to use an effective method of birth control/contraception to prevent
pregnancy until 6 months after discontinuation of the 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 the SCB-313.

Note: Contraceptive methods that are considered highly effective are, for example, total
abstinence, an intrauterine device, a double barrier method (such as condom plus diaphragm
with spermicide), a contraceptive implant, hormonal contraceptives (contraceptive pills,
implants, transdermal patches, hormonal vaginal devices, or injections with prolonged
release), or have a vasectomized partner with confirmed azoospermia.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous
(IV) antibiotics within 2 weeks prior to enrollment.

2. Symptoms or signs (including laboratory tests) of clinically significant concomitant
hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine
diseases.

3. Residual adverse events (AEs) > Grade 2 from previous treatment.

4. Evidence or suspicion of relevant psychiatric impairment including alcohol or
recreational drug abuse.

5. 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 >450 msec at baseline.

6. Uncontrolled hypertension defined as systolic blood pressure =160 mmHg and/or
diastolic blood pressure =100 mmHg confirmed upon repeated measures.

7. Left ventricular ejection fraction <40% as determined by echocardiography performed at
screening or within 90 days prior to enrollment.

8. Prior anti-tumor therapy (chemotherapy) within 2 weeks, hormone therapy or palliative
extra-abdominal radiotherapy within at least 1 week, or small-molecule targeted
therapy within 5 half-lives prior to enrollment. Prior therapy with monoclonal
antibody should be stopped after Investigator's judgement making sure delayed side
effects will not interfere with the dose limiting toxicity (DLT) evaluation period
after SCB-313 therapy.

9. Major surgery within 4 weeks prior to enrollment.

10. Patient with ileus within 30 days prior to screening.

11. Positive serology test for human immunodeficiency virus Type 1 and 2 or known history
of other immunodeficiency disease.

12. Live vaccine within 2 weeks prior to enrollment.

13. Scheduled participation in another clinical study involving an investigational product
or device during the course of this study.

14. Previous treatment with a TRAIL-based therapy or death receptor (DR) 4/5 agonist
therapy.

15. Known or suspected hypersensitivity to any component of the SCB-313.

16. Any further condition which, according to the Investigator, may result in undue risk
of the patient by participating in the present study.

17. Untreated central nervous system metastatic disease, leptomeningeal disease, or cord
compression.

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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 in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Orange Health Service - Orange
Recruitment hospital [3] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [4] 0 0
John Flynn Private Hospital - Tugun
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2800 - Orange
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
4224 - Tugun
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park

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, immunogenicity, and PK/PD
of SCB-313 (recombinant human TRAIL-Trimer fusion protein) administered twice weekly for 2
weeks via IP bolus injection for the treatment of patients with peritoneal malignancies,
including but not limited to peritoneal carcinomatosis, malignant ascites, pseudomyxoma
peritonei, and peritoneal mesothelioma.
Trial website
https://clinicaltrials.gov/show/NCT03443674
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/show/NCT03443674