Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000473561
Ethics application status
Approved
Date submitted
2/04/2024
Date registered
16/04/2024
Date last updated
16/04/2024
Date data sharing statement initially provided
16/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I, Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of OXT-328 in Patients with Chemotherapy-Induced Peripheral Neuropathy. (Part C)
Scientific title
A Phase I, Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of OXT-328 in Patients with Chemotherapy-Induced Peripheral Neuropathy. (Part C)
Secondary ID [1] 311691 0
OXT328-NEU-01
Universal Trial Number (UTN)
Trial acronym
Linked study record
This record is a sub study of ACTRN12624000374561

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy-Induced Peripheral Neuropathy (CIPN) 333153 0
Condition category
Condition code
Neurological 329851 329851 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase Ia/b, randomised double blind, placebo-controlled, multiple dose, multi-cohort study.

Part C: (Multiple Doses at One Dose level) in patients with chemotherapy-induced peripheral neuropathy (CIPN).
Part C may commence following completion of SRC review of Part B (ACTRN12624000374561).

Twenty patients with CIPN will be enrolled to 1 of 2 treatment area groups according to the extremity where patients experience CIPN: Hand (Group 1,) or Foot (Group 2). Following enrolment to either Group 1 or 2, patients will be randomised to receive doses of OXT-328 or placebo administered as a topical gel. Doses will be administered on Days 1 to 28 (inclusive), with the dosing schedule once daily, twice daily or three times daily to be determined based on results from Part B (ACTRN12624000374561), prior to commencement of dosing in Part C.

Dose administration will be performed by site staff and adherence to Intervention will be managed via recording in appropriate drug accountability records.
Intervention code [1] 328154 0
Treatment: Drugs
Comparator / control treatment
The placebo gel contains no active ingredient and is formulated to match the appearance of OXT-328 gel formulation in colour and consistency, and to match the appearance of OXT-328 upon contact with skin. The placebo gel is also odourless and will also be supplied in an identical 50 gram tube as the OXT-328 gel. Composition of the gel includes quinoline yellow, ethanol, hypromellose, xanthan gum, glycerol, sodium citrate, citric acid, trolamine, benzalkonium and purified water.
Control group
Placebo

Outcomes
Primary outcome [1] 337619 0
To evaluate the safety and tolerability of OXT-328 following multiple doses of OXT-328 topical gel compared with placebo in patients with CIPN
Timepoint [1] 337619 0
Adverse events - will be graded using a five-point severity scale (mild, moderate, severe, life-threatening, death) and assessed continuously as they are reported or observed and reviewed daily from Screening until Day 35 (End of Study/Early Termination [EOS/ET]).

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer respiratory rate by manual breath count, temperature by thermometer. Measured from Screening, pre-dose Day 1 0.25 hr, 4hrs post-dose, pre-dose Day 2 - 0.25 hr, 1 hr and 4 hrs post-dose, pre-dose Day 7 1 hr post-dose, pre-dose Day 14 1 hr post-dose, pre-dose Day 28 1 hr post-dose and Day 35 (EOS/ET).

Clinical Laboratory Assessments (haematology, serum chemistry and urinalysis) blood and urine will be collected at Screening, pre-dose Day 1, pre-dose Day 2, pre-dose Day 7, pre-dose Day 14, pre-dose Day 28 and Day 35 (EOS/ET).

Full physical assessment will include at a minimum, assessment of the following: general appearance, head, ears, eyes, nose, and throat examination, neck (including thyroid and nodes), cardiovascular, respiratory, GI, renal, neurological, musculoskeletal, skin and occur at Screening and Day 35 (EOS/ET) with symptom directed assessments to occur at any time pre and post-dose Day 1, Day 2. Day 7, Day 14, and Day 28.

Electrocardiogram (ECG) 12-lead ECG recordings will be obtained in triplicate at Screening, pre-dose Day 1 1 hr post-dose, pre-dose Day 2 1 hr post-dose, pre-dose Day 7 1 hr post-dose, pre-dose Day 28 1 hr post-dose and ET visit.

Local tolerability will be graded using a Local Skin Tolerability Questionnaire and assessed pre-dose Day 14 hrs post-dose, pre-dose Day 2 4 hrs post-dose, pre-dose Day 7, pre-dose Day 14 4 hrs post-dose, pre-dose Day 28 and Day 35 (EOS/ET).

Assessment of use of rescue analgesics will be carried out upon review of patient diary at clinic visits on Day 7, Day 14, and Day 28.
Secondary outcome [1] 432544 0
To evaluate the pharmacokinetics (PK) plasma profile of OXT-328 following multiple topical doses in patients with CIPN.
Timepoint [1] 432544 0
Blood plasma samples to be collected pre-dose Day 1 - 1, 2, 4, 6 and 8 hrs post-dose, pre-dose Day 7 - 1, 2, 4, 6 and 8 hrs post-dose.
Secondary outcome [2] 432545 0
Exploratory Outcome: To evaluate the relief of symptoms of CIPN during treatment with OXT-328 topical gel in patients with CIPN
Timepoint [2] 432545 0
NRS assessment will be conducted at Screening, pre-dose on Day 1 - 1, 2, 6 hrs post-dose, pre-dose Day 2, pre-dose Day 7, pre-dose Day 14, pre-dose Day 28 and Day 35 End of Study/Early Termination Visit (EoS/ETV).
Secondary outcome [3] 432547 0
Exploratory Outcome: To determine the proportion of treatment responders in response to OXT-328 topical gel (Part C).
Timepoint [3] 432547 0
NRS assessment will be conducted at Screening, pre-dose on Day 1 - 1, 2, 6 hrs post-dose, pre-dose Day 2, pre-dose Day 7, pre-dose Day 14, pre-dose Day 28 and Day 35 End of Study/Early Termination Visit (EoS/ETV).
Secondary outcome [4] 433756 0
Exploratory Outcome: To evaluate the relief of symptoms of CIPN during treatment with OXT-328 topical gel in patients with CIPN
Timepoint [4] 433756 0
EORTC QLQ-CIPN20 assessment will be conducted pre-dose on Day 1 and at any time on Day 28.
Secondary outcome [5] 433759 0
Exploratory Outcome: To determine the proportion of treatment responders in response to OXT-328 topical gel (Part C).
Timepoint [5] 433759 0
EORTC QLQ-CIPN20 assessment will be conducted pre-dose on Day 1 and at any time on Day 28.

Eligibility
Key inclusion criteria
Participants will be included in Part C of the study only if they satisfy all the following criteria:
1. Must have given written informed consent, before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2. Male or female, aged greater than or equal to 18 years, inclusive at Screening.
3. Have moderate-to-severe CIPN as defined by a NRS score of greater than or equal to 4 and less than or equal to 8 on a 0 – 10 scale for the participant’s experience of all CIPN-related symptoms.
4. Completion of chemotherapy between 1 to 6 months prior to screening.
5. Participant is otherwise medically healthy (in the opinion of the Investigator [or delegate]), as determined by pre-study medical history and without clinically significant abnormalities including:
a. Physical examination without any additional clinically relevant findings
b. Heart rate in the range of 40 to 100 beats/minute after 5 minutes rest in supine or semi-supine position.
c. Body temperature (tympanic), between 35.5°C and 37.7°C.
d. Electrocardiogram without clinically significant abnormal findings including QT interval corrected for Fredericia (QTcF) < 450 msec for male subjects and < 470 msec for female subjects.
e. No clinically significant findings in serum chemistry, haematology, or urinalysis.
6. Female participants must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a FSH level consistent with postmenopausal status, per local laboratory guidelines), or, if of childbearing potential:
a. Must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test on Day -1, prior to dose administration.
b. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 30 days after the last dose of study drug.
c. If not exclusively in a same-sex relationship, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 30 days after the last dose of study drug.
7. Male participants must:
a. Agree not to donate sperm from the time of signing consent until 90 days after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom plus a highly effective method of contraception) from the time of signing consent until at least 90 days after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from the time of signing consent until at least 90 days after the last dose of study drug.
8. Negative alcohol breath test at Screening or pre-dose on Day 1.
9. Negative urine drugs of abuse test at Screening or pre-dose on Day 1.
10. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded from Part C of the study if there is evidence of any of the following:
1. Current, active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
2. Suffers from frequent or recurrent infections (defined as greater than or equal to 3 recurrent or separate occurrences in the 12 months preceding first study drug administration or 2 recurrent or separate occurrences in the 6 months preceding first study drug administration).
3. Use of antioxidant-containing medications, supplements or products within 30 days prior to the first study drug administration.
4. Use of systemic corticosteroid, sulindac, or any other nonsteroidal anti-inflammatory drugs (NSAID) within 7 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration.
5. Use of tricyclics, serotonin and norepinephrine reuptake inhibitors (SNRIs), sodium channel blockers, and gabapentinoids within 30 days or 5 half-lives of the medication (whichever is longer) prior to first study drug administration.
6. Use of selective serotonin reuptake inhibitors (SSRIs) (citalopram, escitalopram, sertraline, etc.) within 30 days prior to the first study drug administration.
Note: Participant on stable doses of SSRIs is permitted.
7. Experienced myocardial infarction or undergone coronary artery bypass grafting within 6 months of Screening.
8. Diagnosed with congestive heart failure, defined as New York Heart Association (NYHA) Class II-IV.
9. History of hypersensitivity reaction, anaphylaxis or other clinically significant reactions or known allergy to any of the study drug ingredients (including any of its metabolic derivatives – sulindac, sulindac sulfone and sulindac sulfide), or any other NSAIDs.
10. History of or currently existing aspirin-induced asthma, gastric ulcers, non-iatrogenic intestinal perforation, or GI bleeding from NSAID usage for which intervention was required.
11. History of any clinically significant disorder (which, in the opinion of the Investigator [or delegate] would make implementation of the protocol or interpretation of study results difficult, or that would put the subject at risk by participating in the study), including cardiovascular, haematologic, pulmonary, hepatic, renal, gastrointestinal (GI), connective tissue, uncontrolled endocrine/metabolic (including but not limited to diabetes), neurologic, and psychiatric, or any disorder that may prevent the successful completion of the study or influence the absorption, distribution, metabolism, excretion, or action of the study drug (including any of its metabolic derivatives – sulindac, sulindac sulfone and sulindac sulfide).
Note: Participants with history of resolved childhood asthma, history of migraine (if less than or equal to 1 monthly episode and not on preventative medication), or history of non-hospitalised depression (if not on any anti-depressant) will be allowed to participate in the study.
12. Uncontrolled hypertension defined by systolic blood pressure (BP) > 180 mmHg or diastolic BP > 110 mmHg after 5 minutes in supine or semi-supine position.
13. History of surgery within 12 weeks prior to Screening, or surgery planned during the study.
14. Current diagnosis of tumour or metastasis affecting the cervical/lumbosacral plexus and evidence of tumour-associated pain.
15. Currently receiving chemotherapy for the treatment of neoplasia.
16. Experience neuropathic pain due to other conditions, including postherpetic neuralgia, diabetes mellitus, human immunodeficiency virus (HIV) infection, spinal cord injury, and other neurological diseases.
17. Lack of suitable veins for multiple venepunctures/cannulations as assessed by the Investigator or delegate at Screening.
18. Presence of any tattoos, scarring or active skin infection or other condition (including open sores, pressure ulcers, stasis ulcers, or other dermatitides), which (in the opinion of the Investigator [or delegate]) would interfere with skin local tolerability assessments at the study drug application site.
19. Laboratory results at Screening that indicate inadequate renal function (estimated creatinine clearance of < 60 mL/min calculated by the Cockcroft and Gault formula).
20. Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase, alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine transaminase (ALT). Participants with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
21. Liver function tests outside the normal range for bilirubin (more than 1.5-fold above the ULN for total bilirubin).
22. Any clinically relevant laboratory finding or medical condition that could place the subject at risk for participation in the study.
23. Use of topical, non traditional, or non-pharmacological therapy for the treatment of their pain (e.g., chiropractic therapies, alternative medicine therapies, or acupuncture) within 7 days prior to first dose of study drug. Use of paracetamol is allowed if on a stable dose.
24. Currently using any prescription medication or over-the-counter medication/vitamins/supplements/herbal remedies which (in the opinion of the Investigator [or delegate], in consultation with the study medical monitor) may interfere with a participant’s ability to participate in the study or affect trial outcomes.
Note: Use of standard doses (2g/day) of paracetamol is permitted
25. Use of opioid analgesics within 5 half-lives of the medication prior to first dose of study drug.
26. Concurrent enrolment in another clinical study, or participation in another clinical study within 30 days or 5 half-lives of the study drug (whichever is longer) prior to first dose of study drug.
27. Regular consumption of > 10 standard alcoholic drinks/week where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], 30 mL spirit [40% Alc/Vol]).
28. Positive alcohol breath test at Screening or pre-dose on Day 1.
29. Positive urine drugs of abuse test at Screening or pre-dose on Day 1.
30. History of substance abuse or dependency within 12 months prior to Screening, or recreational intravenous drug use within 5 years prior to Screening (by self-declaration).
31. Participant is breastfeeding or pregnant, or planning to breastfeed or become pregnant during the study.
32. Known substance abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the participants inclusion in the clinical study or evaluation of the clinical study results.
33. Positive Hepatitis B surface antigen (HBsAg), Hep C virus antibody, or HIV antibody tests at Screening.
34. Participant has donated blood/blood products, experienced significant (> 400 mL) blood loss within 3 months prior to the first dose administration or receipt of a blood transfusion within 1 year prior to the first dose administration.
35. Any other condition or prior therapy that in the opinion of the Investigator (or delegate) would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All study participants will receive a unique sequential number and will be assigned a randomisation number prior to first dose administration, which corresponds to a study treatment (OXT-328 or placebo). The randomisation schedule will be prepared by an unblinded statistician and maintained under controlled access. A copy of the randomisation schedule will be provided to unblinded personnel responsible for dispensing the study drugs. The unblinded personnel will store the randomisation schedule in a secure, restricted access area. Code break envelopes will be provided to clinic site prior to first dose administration in the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to OXT-328 or placebo will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This is a FIH study for OXT-328. As such, no formal sample size calculations have been performed, and the sample size is empirical.
The sample size of 20 patients with CIPN in Part C are considered adequate to meet the objectives of the study.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/04/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 26243 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 42211 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 316019 0
Commercial sector/Industry
Name [1] 316019 0
Cleothena Enterprises Pty Ltd
Country [1] 316019 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Cleothena Enterprises Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 318171 0
Commercial sector/Industry
Name [1] 318171 0
Avance Clinical Pty Ltd
Address [1] 318171 0
Country [1] 318171 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314843 0
Bellberry Human Research Ethics Committee J
Ethics committee address [1] 314843 0
Ethics committee country [1] 314843 0
Australia
Date submitted for ethics approval [1] 314843 0
20/12/2023
Approval date [1] 314843 0
23/02/2024
Ethics approval number [1] 314843 0
2023-12-1584

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132898 0
Dr Christopher Argent
Address 132898 0
Scientia Clinical Research, Bright Building, Level 5, Corner High and Avoca Street, Randwick, NSW 2031
Country 132898 0
Australia
Phone 132898 0
+61 458 639 115
Fax 132898 0
Email 132898 0
[email protected]
Contact person for public queries
Name 132899 0
Christopher Argent
Address 132899 0
Scientia Clinical Research, Bright Building, Level 5, Corner High and Avoca Street, Randwick, NSW 2031
Country 132899 0
Australia
Phone 132899 0
+61 458 639 115
Fax 132899 0
Email 132899 0
[email protected]
Contact person for scientific queries
Name 132900 0
Christopher Argent
Address 132900 0
Scientia Clinical Research, Bright Building, Level 5, Corner High and Avoca Street, Randwick, NSW 2031
Country 132900 0
Australia
Phone 132900 0
+61 458 639 115
Fax 132900 0
Email 132900 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.