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Trial registered on ANZCTR


Registration number
ACTRN12618000675224
Ethics application status
Approved
Date submitted
13/03/2018
Date registered
24/04/2018
Date last updated
20/11/2018
Date data sharing statement initially provided
20/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
INB03 for patients with metastatic cancer with increased inflammatory biomarkers in peripheral blood
Scientific title
Phase 1 open-label, dose escalation study of INB03 in patients with metastatic cancer with increased inflammatory biomarkers in peripheral blood
Secondary ID [1] 294326 0
INMB-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
solid epithelial tumour 307047 0
Epithelial Cancer 307156 0
Cancer 307157 0
Condition category
Condition code
Cancer 306149 306149 0 0
Breast
Cancer 306150 306150 0 0
Lung - Non small cell
Cancer 306151 306151 0 0
Malignant melanoma
Cancer 306152 306152 0 0
Kidney
Cancer 306153 306153 0 0
Bowel - Anal
Cancer 306154 306154 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 306155 306155 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 306156 306156 0 0
Oesophageal (gullet)
Cancer 306157 306157 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will consist of 3 dosing cohorts. In each cohort, 3 participants will be treated with once weekly subcutaneous injections of INB03 at a dose of 0.3 (no more than 30 mg), 1.0 (no more than 100 mg) or 3.0 mg/kg (no more than 220 mg or 2 vials of INB03), respectively. INB03 will be administered weekly for 9 months or until disease progression as determined by the PI and/or participant intolerance as determined by the Principal Investigator (PI). However, participants may continue INB03 therapy at any time, including after study end at Month 9, on a compassionate use basis if the attending physician believes the subject is benefiting from the therapy in any way.
INB03 will be administered by a study nurse at clinical investigation site from Day 1 till Day 85 visits. At the discretion of the investigator patients may be allowed to self-administer INB03 at home from Month 4 visit onwards. Subjects who undergo home-administration of INB03 will be asked to bring all used, partially used, or unused contains to study staff at each study visit for completion of drug accountability and monitor adherence.
All subjects will receive their assigned INB03 dose through Month 3. After all subjects have
completed 3 months of therapy, an interim analysis will be conducted and an optimal dose for the Phase 2 trial will be determined by the Data Safety Monitoring Board (DSMB). Further dosing of INB03 after Month 3 may be adjusted to the selected dosage for Phase 2.
Intervention code [1] 300635 0
Treatment: Drugs
Comparator / control treatment
This is a dose selection trial of INB03. All patients will receive INB03 although at different dose levels: 0.3, 1.0 and 3.0 mg/kg.
Control group
Dose comparison

Outcomes
Primary outcome [1] 305165 0
Safety and tolerability of INB03 given by sub-cutaneous injection once a week. This outcome is incidence of grade 3 or greater AEs and SAEs as graded by NCI CTCAE criteria v 5.0.
Timepoint [1] 305165 0
Day 1, 3, 5, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 & 85
Primary outcome [2] 305166 0
Evaluate the pharmacokinetics (PK) of single dose and multiple doses of INB03. Due to the cross-reactivity of INB03 and serum soluble TNF in assay systems, the FDA recommended the Sponsor use serum soluble TNF levels as a measure of drug level during the clinical trials. An abbreviated PK study format will be used.
Timepoint [2] 305166 0
Four time points will be studied for the first dose PK and trough levels will be monitored for the multi-dose PK. Specifically measurements of human TNF-Alpha levels will be tested in blood samples collected at time 0, 1, 4 and 8 hours after the first INB03 dosing on Day 1. Trough levels will continue to be collected on Day 3 and prior to successive doses on Day 8, 15, 22, 29, 43, 57, 85, and Month 4-9.
Primary outcome [3] 305167 0
The study will examine the following efficacy parameters throughout the study:
- change in hsCRP serum levels
Timepoint [3] 305167 0
Screening, Days 1, 8, 29, 43, 57, 71, 85, Months 4, 5, 6, 7, 8 and 9
Secondary outcome [1] 344698 0
Survival via hospital visits and review of medical records
Timepoint [1] 344698 0
Day 85, Month 6 and 9
Secondary outcome [2] 345551 0
Evaluate the correlation of immune activation with clinical response as measured by hsCRP, flow monitoring for immune cell phenotypes, and inflammatory cytokines including TNFa, interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and IL 1ß
Timepoint [2] 345551 0
Day 29, Day 85, Month 6

Eligibility
Key inclusion criteria
1. Subject is greater than or equal to 18 years old, male or female.
2. Subject has histopathological diagnosis of epithelial cancer and meets the following criteria:
a. Diagnosed with stage 3 or 4 cancer of the lung, breast, upper or lower gastrointestinal
tract, kidney, or skin (melanoma only)
b. Diagnosed with cancer that is unlikely to clinically benefit from any other currently
available therapies.
c. There is no limit to the number of prior therapies allowed.
3. Subject has an hsCRP >10 mg/L that cannot be attributed to an infection.
4. Subject has a life expectancy > 4 months in the opinion of the Investigator.
5. Subject has adequate organ and marrow function (as defined below):
a. Serum creatinine less than or equal to 1.5 X upper limit of normal (ULN), or calculated creatinine clearance greater than or equal to 60 ml/min/1.73m2 as measured by Cockcroft-Gault
b. Aspartate aminotransferase and alanine aminotransferase levels less than or equal to 3 X ULN.
c. Total bilirubin < 1.5 X ULN, unless known diagnosis of Gilbert’s syndrome
d. Absolute neutrophil greater than or equal to 1,500/mm3
e. Platelet count greater than or equal to 50,000/mm3
f. Hemoglobin greater than or equal to 10 mg/dL (transfusion to obtain hemoglobin greater than or equal to 10 mg/dL within 24 hours prior to dosing is allowed)
6. Subject must be at least 4 weeks from previous therapy (eg, chemotherapy, hormonal therapy,
radiation therapy, immunotherapy and monoclonal antibodies, alternative therapy or
investigational therapeutic agents).
7. Subjects who have had major surgery must be fully recovered and require a recovery period of greater than or equal to 4 weeks prior to study Screening.
8. Subject must have an Eastern Cooperative Oncology Group performance status less than or equal to 2.
9. Subjects who are women of childbearing potential must not be pregnant and breastfeeding. Male and female subjects of childbearing potential must agree to use adequate contraception (barrier method or abstinence) for the duration of study therapy and for 3 months after the last dose of INB03. Any pregnancy that occurs for study participants should be monitored for potential side effects.
a. Women must discontinue any hormonal forms of birth control at least 4 weeks
prior to initiating the study.
10. Subject, or legal guardian, must be able to understand and voluntarily sign a written informed consent, and are willing and able to comply with the protocol requirements.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has sarcoma, haematological cancer or primary cancer of the central nervous system. Patients with brain metastasis from an epithelial cancer are eligible for treatment.
2. Subject has an active infection. Subjects may become eligible once infection has resolved and they are at least 7 days from completion of antibiotics and hsCRP returned to baseline.
3. Subject is currently taking concomitant corticosteroids or other immunosuppressive drugs. (Note, inhaled steroids for asthma and chronic obstructive pulmonary disease is accepted)
4. Subject is currently taking concomitant thalidomide or a tumour necrosis factor (TNF) alpha- inhibitors.
5. Subject has a resting, room air oxygen partial pressure (PO2) < 90% at Screening.
6. Subject has impaired cardiac function or clinically significant cardiac disease including the following:
a. New York Heart Association grade III or IV congestive heart failure.
b. Myocardial infarction within the last 6 months prior to dosing with INB03
c. Impaired left ventricular ejection fraction (< 40%) as assessed according to institutional
standards.
7. Subject has human immunodeficiency virus infection or an active hepatitis C or hepatitis B virus infection.
8. Subject has any other condition or finding that in the opinion of the PI or Sponsor Medical Monitor may render the subject at excessive risk for treatment complications or may not be able provide evaluable outcome information.
9. Subject has shown lack of recovery of prior adverse events (AEs) to Grade less than or equal to 1 severity (National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] v 5.0) (except alopecia) due to therapy administered prior to the initiation of study drug dosing by the time of study Screening. Stable persistent grade 2 peripheral neuropathy may be allowed as determined on a case-by-case basis at the discretion of the PI or Medical Monitor.
10. Subject has uncontrolled seizures as determined by the PI.
11. Subject concomitant use of complementary or alternative medication or other agents
(investigational therapeutic agents) will not be allowed without approval of a PI or
sub-investigator. Every effort will be made to maximize subject safety and minimize changes in chronic medications.

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 design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
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 in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 10380 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment hospital [2] 10381 0
Southern Medical Day Care Centre - Wollongong
Recruitment postcode(s) [1] 22058 0
5000 - Adelaide
Recruitment postcode(s) [2] 22059 0
2500 - Wollongong

Funding & Sponsors
Funding source category [1] 298972 0
Commercial sector/Industry
Name [1] 298972 0
INmune Bio Australia Pty Ltd
Address [1] 298972 0
Suite 4, 16 Ord Street
West Perth WA 6005
Country [1] 298972 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
CTI Clinical Trial and Consulting Services Australia Pty Ltd
Address
Level 13, 167 Macquarie Street
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 298195 0
None
Name [1] 298195 0
Address [1] 298195 0
Country [1] 298195 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299903 0
Bellberry Human Research Ethics Committee G (EC00458)
Ethics committee address [1] 299903 0
129 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 299903 0
Australia
Date submitted for ethics approval [1] 299903 0
07/03/2018
Approval date [1] 299903 0
21/05/2018
Ethics approval number [1] 299903 0
2018-03-166

Summary
Brief summary
The purpose of this study is to determine the safety and tolerability of INB03 in patients with metastatic cancer.

Who is it for?
You may be eligible for this study if you have epithelial cancer of the lung, breast, upper or lower gastrointestinal tract, kidney, or skin (melanoma only).

Study details.
All participants will receive INB03 subcutaneously once a week for up to 9 months. There will be three groups who each receive a different dose. As a part of the clinical research study patients will have regular blood tests, physical examinations, will have to complete short questionnaires on their depression, sleep and fatigue.

This is first in the human clinical research study and its results will help to determine if INB03 is safe and is tolerated well. Dose of INB03 selected in this study will be used in future study intended for patients with metastatic cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81934 0
Dr Raymond J Tesi
Address 81934 0
INmune Bio Inc.
476 Massachusetts Ave, Unit 2
Boston, MA 02118
Country 81934 0
United States of America
Phone 81934 0
+1 510 396 57095
Fax 81934 0
Email 81934 0
rtesi@inmunebio.com
Contact person for public queries
Name 81935 0
Mr Pavels Anetko
Address 81935 0
CTI Clinical Trial and Consulting Services Australia Pty Ltd
Level 13, 167 Macquarie Street
Sydney NSW 2000
Country 81935 0
Australia
Phone 81935 0
+61 2 8667 3052
Fax 81935 0
Email 81935 0
panetko@ctifacts.com
Contact person for scientific queries
Name 81936 0
Dr Raymond J Tesi
Address 81936 0
INmune Bio Inc.
476 Massachusetts Ave, Unit 2
Boston, MA 02118
Country 81936 0
United States of America
Phone 81936 0
+1 510 396 57095
Fax 81936 0
Email 81936 0
rtesi@inmunebio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data will be analyzed in aggregate and reported as such to the PI, participants if interested, clinical community (via public disclosure in presentations, publications, investigator brochure and other public forums), to regulatory authorities by regulatory filings on this trial and related future trials, and to the investor community at private and public meetings.
There will be no patient identifier data attached to any of the aggregate data. The only place the patient name can be associated with the data is at the CRO where the original enrollment occurs. After enrollment, all data entry is based on an anonymized patient identifier.
What supporting documents are/will be available?
No other documents available
Summary results
No Results