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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06402123




Registration number
NCT06402123
Ethics application status
Date submitted
2/05/2024
Date registered
7/05/2024

Titles & IDs
Public title
A Phase 2b Study of Zagociguat in Patients With MELAS
Scientific title
Phase 2b Randomized, Double-blind, Placebo-controlled Crossover Study Evaluating the Efficacy and Safety of Zagociguat in Participants With MELAS (PRIZM)
Secondary ID [1] 0 0
TIS6463-203
Universal Trial Number (UTN)
Trial acronym
PRIZM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome) 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Renal and Urogenital 0 0 0 0
Kidney disease
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - zagociguat 15mg
Treatment: Drugs - zagociguat 30mg
Treatment: Drugs - Placebo

Experimental: Placebo then Zagociguat 15mg - Participants first receive placebo once a day for 12 weeks. Then after a 4 week washout, they receive zagociguat 15 mg once a day for 12 weeks.

Experimental: Zagociguat 15mg then Placebo - Participants first receive zagociguat 15 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks.

Experimental: Placebo then Zagociguat 30mg - Participants first receive placebo once a day for 12 weeks. Then after a 4-week washout, they receive zagociguat 30 mg once a day for 12 weeks.

Experimental: Zagociguat 30mg then Placebo - Participants first receive zagociguat 30 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks.


Treatment: Drugs: zagociguat 15mg
Once-daily oral tablets

Treatment: Drugs: zagociguat 30mg
Once-daily oral tablets

Treatment: Drugs: Placebo
Once-daily oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
• PROMIS Fatigue MELAS Short Form scores • Memory composite scores (One Card Learning and One Back Tests) • International Digit Symbol Substitution Test scores
Timepoint [1] 0 0
Weeks 9 through 12 of each treatment period
Primary outcome [2] 0 0
Incidence of Treatment-emergend Adverse Events (TEAEs)
Timepoint [2] 0 0
Weeks 1 through washout for treatment period 1 and Weeks 1 through follow-up for treatment period 2
Secondary outcome [1] 0 0
Number of repetitions completed during the 30-second sit-to-stand test
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Groton Maze Learning Test (GMLT) scores
Timepoint [2] 0 0
Week 9 through 12
Secondary outcome [3] 0 0
PROMIS Cognitive Function MELAS Short Form (PCFM-SF) score
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Plasma concentrations of GDF-15
Timepoint [4] 0 0
Week 12

Eligibility
Key inclusion criteria
1. Signed consent form.
2. 18 to 75 years of age.
3. Diagnosed with MELAS based on the presence of each of the following criteria:

1. A documented pathogenic variant in a mitochondrial DNA (mtDNA) gene.
2. History of one or more stroke-like episodes (SLEs) with magnetic resonance imaging (MRI) findings consistent with stroke-like lesions.
4. Scores below normal average on composite memory score from One Back and One Card Learning tests.
5. Reports fatigue due to MELAS.
6. Can complete at least 1 sit-to-stand in the 30-second test interval.
7. Completes all at-home weekly activities independently during the Screening Period (caregiver may help set up device/app, log-in, etc.).
8. Other criteria per the protocol.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Systolic blood pressure (BP) 90 mmHg or diastolic BP 60 mmHg.
2. Orthostatic hypotension when measured after standing from a semi-recumbent/supine position.
3. Active cancer significant enough to confound the results of this study.
4. Severe gastrointestinal dysmotility that may impact participation.
5. Recent history (within last 6 months) of platelet dysfunction, hemophilia, von Willebrand disease, coagulation disorder, other bleeding diathesis condition(s), or significant, nontraumatic bleeding episodes.
6. History of spontaneous fracture(s) that in the investigator's opinion represents a safety risk for trial participation.
7. Current use of prohibited medication (reviewed by investigator).
8. Any medical or other condition that the investigator thinks would preclude study participation.
9. Other exclusion criteria per protocol.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
15/07/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2025
Actual
Sample size
Target
44
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Neuroscience Research Australia - Sydney
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
NSW 2031 - Sydney
Recruitment postcode(s) [2] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Canada
State/province [12] 0 0
Winnipeg
Country [13] 0 0
Germany
State/province [13] 0 0
Bonn
Country [14] 0 0
Germany
State/province [14] 0 0
Munich
Country [15] 0 0
Italy
State/province [15] 0 0
Milan
Country [16] 0 0
Italy
State/province [16] 0 0
Pisa
Country [17] 0 0
Italy
State/province [17] 0 0
Roma
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Tisento Therapeutics
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

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

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06402123