Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000151437
Ethics application status
Approved
Date submitted
24/01/2025
Date registered
7/02/2025
Date last updated
7/02/2025
Date data sharing statement initially provided
7/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
An open-label study to evaluate the safety and efficacy of modified-release calcium formate in adult patients with homocystinuria
Scientific title
A phase 2a, open-label study to evaluate the efficacy and long-term safety of modified-release calcium formate to reduce elevated plasma homocysteine (Hcy) levels in adult patients with homocystinuria.
Secondary ID [1] 313809 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
homocystinuria 336445 0
Condition category
Condition code
Metabolic and Endocrine 332965 332965 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients eligible to participate will receive 2.6 g calcium formate (corresponding to 1.8 g formate) per day for the first two weeks. Daily dosing will be divided into 1.3 g calcium formate in the morning and 1.3 g in the evening. At week 3, dosing may be up-titrated (increments of 300 mg formate and not exceeding 2.4 g formate/day). The decision to up titrate will be dependent on plasma homocysteine levels measured at the day 14 visit. The total duration of the intervention is 52 weeks.
The investigational treatment will be administered orally as 434 mg calcium formate (300 mg formate) per tablet evenly divided between the morning and the evening up to the required dose.
Tablets will be returned after each clinic visit and compared to the expected number of tablets returned to calculate compliance.
Intervention code [1] 330395 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340503 0
Change in plasma homocysteine levels
Timepoint [1] 340503 0
Percentage change in the geometric mean of Week 6 and Week 10 plasma homocysteine values compared to Baseline
Secondary outcome [1] 444284 0
To evaluate the safety and tolerability of daily administration of calcium formate in participants with homocystinuria. This will be assessed as a composite outcome.
Timepoint [1] 444284 0
Change in levels as compared to baseline at week 2, week 6, week 10, week 26 and week 52 after commencing formate treatment
Secondary outcome [2] 444285 0
To determine the effect of calcium formate on anxiety in participants with homocystinuria
Timepoint [2] 444285 0
Change in mean weekly Hamilton Anxiety Rating Scale scores from baseline to 6 and 10 weeks after daily formate treatment.

Eligibility
Key inclusion criteria
1. Male and female aged 18- 65 years, inclusive.
2. Homocystinuria as confirmed by prior diagnosis.
3. Plasma Hcy more than 50 µM (rounded to the nearest whole number) and documentation of previous Hcy more than 70 µM.
4. Plasma methionine levels less than 800 µmol/L
5. Willing to maintain a stable diet (plus/minus 20% variability of daily protein intake) with no significant modifications while on study and complete a daily diet diary as requested.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Changes to current medications or commencement of any new medications, including prescription drugs (except hormonal contraception), within 28 days prior to the Screening Visit and during the study treatment phase.
2. Currently taking calcium supplements and where these supplements cannot be replaced by calcium formate
3. Known history of hypercalcemia
4. Known history of any severe cardiovascular disorder not including previous thromboembolic events
5. History of hypersensitivity to formate supplements that, in the judgment of the investigator, puts the participant at unacceptable risk for adverse events (AEs)
6. Known intolerance to any of the investigational product excipients, particularly lactose

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
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
12/02/2025
Actual
Date of last participant enrolment
Anticipated
12/08/2025
Actual
Date of last data collection
Anticipated
12/08/2026
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC

Funding & Sponsors
Funding source category [1] 318275 0
Commercial sector/Industry
Name [1] 318275 0
SubRed Therapeutics Pty Ltd
Country [1] 318275 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
SubRed Therapeutics Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 320662 0
None
Name [1] 320662 0
Address [1] 320662 0
Country [1] 320662 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316915 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 316915 0
Ethics committee country [1] 316915 0
Australia
Date submitted for ethics approval [1] 316915 0
06/09/2024
Approval date [1] 316915 0
12/11/2024
Ethics approval number [1] 316915 0

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

Contacts
Principal investigator
Name 139422 0
Dr Drago Bratkovic
Address 139422 0
Royal Adelaide Hospital, 1 Port Road, Adelaide SA 5000
Country 139422 0
Australia
Phone 139422 0
+61 08 8161 7295
Fax 139422 0
Email 139422 0
[email protected]
Contact person for public queries
Name 139423 0
William McNamee
Address 139423 0
SubRed Therapeutics Pty Ltd. Level 32, 360 Collins Street, Melbourne 3000, Victoria
Country 139423 0
Australia
Phone 139423 0
+61 455738530
Fax 139423 0
Email 139423 0
[email protected]
Contact person for scientific queries
Name 139424 0
William McNamee
Address 139424 0
SubRed Therapeutics Pty Ltd. Level 32, 360 Collins Street, Melbourne 3000, Victoria
Country 139424 0
Australia
Phone 139424 0
+61 455738530
Fax 139424 0
Email 139424 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Summaries and statistics will be published but due to the ultrararity of the disease as well confidentiality and ethics reasons IPD will not be shared.



What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Ethical approval    2024HRE00230 Bratkovic - APPROVAL Letter.pdf.pdf


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.