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Trial registered on ANZCTR


Registration number
ACTRN12620000440921
Ethics application status
Approved
Date submitted
6/03/2020
Date registered
6/04/2020
Date last updated
6/04/2020
Date data sharing statement initially provided
6/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Trial of ALMB-0168 in Patients with Malignant Bone Disease
Scientific title
Phase 1, Multicenter, First-in-Human Dose Escalation Study of ALMB-0168 Administered IV as a Single Agent to Patients with Malignant Bone Disease
Secondary ID [1] 300725 0
ALMB-0168-AU-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteosarcoma or any other solid tumor cancer with bone metastases 316544 0
Condition category
Condition code
Cancer 314786 314786 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will receive a weight-based single dose ALMB-0168 as IV injection at one of the 7 dose levels (1mg/kg to 3mg/kg, 6mg/kg, 12mg/kg, 20mg/kg, 25mg/kg and 30mg/kg) on Day 1 of every 21-day cycle for up to 6 months or maximally 8 cycles. As this is an open-label study, no randomisation will be performed. Assignment of a patient to a particular dose level will be coordinated by the sponsor upon patient registration.
Treatment will be discontinued when disease progression or a change of therapy is necessary. Per Investigator's discretion, ALMB-0168 treatment may be given for longer term to subjects who can continue benefit from it.
Intervention code [1] 317045 0
Treatment: Drugs
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323144 0
The primary outcome is dose-limiting toxicity (DLT), from day 1 to day 21 during the first cycle of the treatment (21 days) after study drug administration. Toxicities will be assessed by performing physical examination, vital signs, ECG, laboratory testing and graded according to NCI-CTCAE version 5.0.
Timepoint [1] 323144 0
Timepoint: The first 3 weeks of first dosing will be defined as DLT evaluation period i.e. Day 1 to Day 21.
DLT assessment to be performed at the end of Cycle 1 on Day 21 or pre-dose Cycle 2 on Cycle 2 Day 1 (i.e. Cycle 1 Day 22) for participants remaining on study.
Secondary outcome [1] 380952 0
Other safety variables including adverse events (AEs), vital signs measurements, lab values, ECGs etc. Those safety parameters will be collected from the start of study drug administration to the end of study (28 days after the last dose) by weekly visit to the clinic (cycles1&2) and once every 3 weeks (cycle3 and after), and performing physical examinations, obtaining vital signs and ECG readings. Incidence of treatment-emergent AEs (TEAEs) will be graded according to NCI CTCAE v5.0.
Timepoint [1] 380952 0
Timepoint: All patients will be closely monitored and will be seen at the clinic on a weekly basis then approximately 28 days after the last treatment and will be followed up for up to one years to evaluate longer term outcomes.
Secondary outcome [2] 381470 0
Pharmacokinetic (PK) parameters such as Cmax, tmax,AUC0-t, AUC0-8 (first dose only), t1/2, CL, and Vz. These parameters will be calculated from serum concentration of ALMB-0168 measured by ELISA using blood samples collected at the following time points:
Cycle 1, Day 1 - Predose, postdose time after end of infusion (immediately, 1 hour, 2 hours, 4 hours, 8 hours);
Cycle 1 Day 2 - Approx. 24 hours following dosing on Day 1
Cycle 1, Day 8 and 15 - During clinic visit
Cycle 2 and every subsequent cycle - Day 1 - pre-dose only
End of Study Visit - 28 days after last dose
Timepoint [2] 381470 0
All patients will be closely monitored and will be seen at the clinic on a weekly basis then approximately 28 days after the last treatment and will be followed up for up to one years to evaluate longer term outcomes.
Secondary outcome [3] 381712 0
The emergence of antibodies to ALMB-0168 to assess immunogenicity of ALMB-0168
Timepoint [3] 381712 0
Blood samples for the determination of antibodies to ALMB-0168 will be obtained at the following timepoints: Cycles 1 & 2 - Day 1 (pre-dose) and Day 15, Cycle 3 and all subsequent cycles - Day 1 (pre-dose).

Eligibility
Key inclusion criteria
1. Pathological confirmation (histological or cytological) of cancer: Osteosarcoma or any other solid tumor cancer.
2. Presence of either:
a. Locally advanced osteosarcoma considered to be incurable by the investigator and for which there is no available therapies;
b. Bone metastatic cancer considered to be incurable by the investigator and for which available anti-cancer therapy has been exhausted, refused or not tolerated.
3. Male or female 16 years of age or older for patients with osteosarcoma, or 18 years or older for patients with all other tumor types.
4. ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0, 1 or 2.
5. Either measurable or non-measurable disease. Non-measurable disease should be assessable by conventional imaging techniques including isotope bone scans, CT or MRI scans.
6. Adequate major system function defined as:
a. Bone marrow reserve:
Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L;
Platelet count greater than or equal to 750 x 10^9/L;
Hemoglobin greater than or equal to 9 g/dL without transfusion in the last 14 days (the patient needs to be transfusion independent);
b. Hepatic function:
Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (unless the patient has Grade 1 bilirubin elevation due to Gilbert’s disease or a similar syndrome involving slow conjugation of bilirubin);
Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and/or alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) less than or equal to 3 x ULN (less than 5 x ULN if liver metastases);
c. Renal function:
Normal serum creatinine less than or equal to 1.5 mg/dL (133 µmol/L) OR calculated creatinine clearance greater than or equal to 50 mL/min. (Cockroft - Gault formula);
d. Coagulation:
Adequate coagulation parameters defined as International Normalization Ratio (INR) less than or equal to 2.
7. Male patients with female partners of childbearing potential and women patients of childbearing potential are required to use two forms of acceptable contraception, including 1 barrier method, during their participation in the study and for 30 days following last dose. Male patients must also refrain from donating sperm during their participation in the study.
8. Life expectancy greater than or equal to 3 months.
9. Willingness and ability to comply with study and follow-up procedures.
10. Ability to understand the nature of this study and give written informed consent.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Most recent chemotherapy less than or equal to 14 days or have residual NCI CTCAE greater than or equal to Grade 1 chemotherapy-related side effects, with the exception of alopecia.
2. Use of any experimental study drug less than or equal to 21 days or 5 half-lives (whichever is shorter) prior to the first dose of ALMB-0168. For study drugs for which 5 half-lives is is less than or equal to 21 days, a minimum of 10 days between termination of the study drug and administration of ALMB-0168 is required.
3. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered less than or equal to 28 days or limited field radiation for palliation less than or equal to 7 days prior to starting study drug or has not recovered from side effects of such therapy.
4. Major surgical procedures less than or equal to 28 days of beginning study drug, or minor surgical procedures less than or equal to 7 days. No waiting required following port-a-cath placement.
5. Previously brain metastases or patients with known brain or CNS injuries.
6. Leptomeningeal metastases or spinal cord compression due to disease.
7. Pregnant or lactating.
8. Acute or chronic liver, renal, or pancreas disease.
9. Uncontrolled systemic disease.
10. Any of the following cardiac diseases currently or within the last 6 months:
- Left ventricular ejection fraction (LVEF) less than 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO);
- QTc interval greater than 470 ms on screening electrocardiogram (ECG);
- Unstable angina pectoris;
- Congestive heart failure (New York Heart Association [NYHA] greater than or equal to Grade 2;
- Acute myocardial infarction;
- Conduction abnormality not controlled with pacemaker or medication;
- Significant ventricular or supraventricular arrhythmias. (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible.)
11. Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] greater than 180 mmHg or diastolic blood pressure (DBP) greater than 100 mmHg) (patients with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment).
12. Serious active infection at the time of treatment (no systemic intravenous antibiotics within 14 days; oral antibiotics is allowed), or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
13. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C.
14. Presence of other active cancers, or history of treatment for invasive cancer less than or equal to 3 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
15. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

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
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The total number of patients to be enrolled in the dose escalation portion of the study is dependent upon the observed safety profile, which will determine the number of patients per dose cohort, as well as the number of dose escalations required to achieve the MTD and subsequent RP2D. Based on the standard "3+3"design, the number of patients enrolled for the entire study will not be less than 2 and not more than 46, including up to 10 patients with osteosarcoma or other bone metastatic disease who will be treated in the final RP2D dose expansion group. The actual number depends on the number of dose levels evaluated and the toxicity documented.

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 in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 16063 0
Scientia Clinical Research - Randwick
Recruitment hospital [2] 16066 0
Flinders Private Hospital - Bedford Park
Recruitment hospital [3] 16067 0
Peninsula Private Hospital - Frankston - Frankston
Recruitment postcode(s) [1] 29576 0
2031 - Randwick
Recruitment postcode(s) [2] 29579 0
5042 - Bedford Park
Recruitment postcode(s) [3] 29580 0
3199 - Frankston

Funding & Sponsors
Funding source category [1] 305173 0
Commercial sector/Industry
Name [1] 305173 0
AlaMab Therapeutics, Inc.
Address [1] 305173 0
AlaMab Therapeutics Inc.
A subsidiary of CSPC Pharmaceutical Group, Ltd.
11550, IH10 W
San Antonio, Texas, USA
Country [1] 305173 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Avance Clinical Pty Ltd
Address
Level 1, 2 Ann Nelson Drive
Thebarton SA 5031 Australia
Country
Australia
Secondary sponsor category [1] 305534 0
None
Name [1] 305534 0
Address [1] 305534 0
Country [1] 305534 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305535 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 305535 0
123 Glen Osmond Road
Eastwood SA 5063, Australia
Ethics committee country [1] 305535 0
Australia
Date submitted for ethics approval [1] 305535 0
27/11/2019
Approval date [1] 305535 0
06/02/2020
Ethics approval number [1] 305535 0
Application # 2019-11-1014

Summary
Brief summary
The purpose of this study is to test the safety of a new medication (called ALMB-0168) in people with malignant bone cancer lesions either from bone cancer or from migration of other cancers.

Who is it for?

You may be eligible for this study if you are aged 16 or older, and have confirmed bone cancer (osteosarcoma) or cancer cells in the bone originated from other cancers which has been deemed untreatable.

Study details

All participants in this study will receive the active medication ALMB-0168. The dose will depend on when the participant enrolls in the study. The medication is administered through a needle in the arm, and will continue for up to 6 months. As part of this study, all participants will have additional blood tests, imaging scans and answer questions regarding to your health.

It is hoped this research will demonstrate the safety of ALMB-0168 and find the ideal dose for larger-scale studies.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100706 0
Dr Charlotte Lemech
Address 100706 0
Scientia Clinical Research
5th Floor, Bright Building
Corner High and Avoca Street
Randwick NSW 2031
Country 100706 0
Australia
Phone 100706 0
+61 293825807
Fax 100706 0
Email 100706 0
charlotte.lemech@scientiaclinicalresearch.com.au
Contact person for public queries
Name 100707 0
Dr Yanfeng Zhang
Address 100707 0
AlaMab Therapeutics Inc.
A subsidiary of CSPC Pharmaceutical Group, Ltd.
11550 West Interstate 10
San Antonio, TX 78230
USA
Country 100707 0
United States of America
Phone 100707 0
+15176670767
Fax 100707 0
Email 100707 0
Yanfeng.Zhang@alamab.com
Contact person for scientific queries
Name 100708 0
Dr XiuGao Yang
Address 100708 0
CSPC Pharmaceutical Group Ltd.
Clinical Development Division
57th Floor SOHO The Exchange
No. 299 Tongren Road
Jang’an District, Shanghai 200040, China
Country 100708 0
China
Phone 100708 0
+8602160677906
Fax 100708 0
Email 100708 0
yangxiugao@mail.ecspc.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and intellectual property considerations
What supporting documents are/will be available?
No other documents available
Summary results
No Results