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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
28/01/2022
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 tumour cancer.
2. Presence of either:
a. Locally advanced or relapsed osteosarcoma considered to be incurable by the investigator and for which there is no available therapies;
b. Advanced solid tumour with bone metastatic cancer considered to be incurable by the investigator and for which available anti-cancer therapy has been exhausted, refused or not tolerated. Breast Cancer (BC) or Prostate Cancer (PC) subjects with bone metastases and who have been under hormonal therapy as Standard of Care (SOC) for underling cancer for at least 3 months and with stable dose and clinical status maybe allowed to enrol. The same applies to SOC bisphosphonates and denosumab, which are also allowable if the subject has been receiving this treatment for a period of at least 3 months at a stable dose prior to screening.
3. Male or female 16 years of age or older for subjects with osteosarcoma, or 18 years or older for subjects with all other tumour 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 x109/L; Platelet count greater than or equal to 100 x 109/L; Haemoglobin greater than or equal to 90 g/L
b. Hepatic function: Total bilirubin lesser than or equal to1.5 x upper limit of normal (ULN) Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and/or alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) lesser than or equal to 3 x ULN (lesser than 5 x ULN if liver metastases);
c. Renal function: Normal serum creatinine lesser than or equal to 1.5 mg/dL (133 µmol/L) OR calculated creatinine clearance greater than or equal to 50 mL/min.
d. Coagulation: Adequate coagulation parameters defined as International Normalization Ratio (INR) lesser than or equal to 2.
7. Male participants with female partners of childbearing potential and women participants 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 subjects 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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Most recent chemotherapy lesser than or equal to14 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 lesser 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 lesser than or equal to 21 days such as tyrosine kinase inhibitor (TKI), a minimum of 10 days between termination of the study drug and administration of ALMB-0168 is required. For certain immune-oncology drugs that have longer half-lives, a washout period of 4 weeks may be required.
3. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered lesser than or equal to 28 days or limited field radiation for palliation lesser 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 lesser than or equal to 28 days of beginning study drug, or minor surgical procedures lesser than or equal to 7 days. No waiting required following port-a-cath placement.
5. Brain metastases or CNS injuries / abnormalities by history or as determined by brain MRI.
6. Leptomeningeal metastases or spinal cord compression due to disease.
7. Pregnant or lactating.
8. Any of the following cardiac diseases currently or within the last 6 months:
- Left ventricular ejection fraction (LVEF) lesser than 45% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO);
- QTc interval greater than 470 msec for females and greater than 450 msec for men on screening electrocardiogram (ECG);
- Unstable angina pectoris;
- New York Heart Association Class III or IV heart failure, acute myocardial infarction, angina pectoris, uncontrolled arrhythmia, acute coronary syndromes, stent placement, uncontrolled hypertension
9. 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 subject to receive protocol treatment.
10. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C.
11. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin
that has undergone potentially curative therapy or in situ cervical cancer
12. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
13. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.

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
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
15/04/2020
Actual
23/10/2020
Date of last participant enrolment
Anticipated
27/08/2021
Actual
6/01/2021
Date of last data collection
Anticipated
29/10/2022
Actual
12/05/2021
Sample size
Target
35
Accrual to date
Final
2
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.
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
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
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
Yanfeng Zhang
Address 100707 0
AlaMab Therapeutics Inc.
302 Carnegie Center, Suite 100
Princeton, NJ 08540, 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
Hua Lv
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
lvhua@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 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.