An open-label extension study evaluating the safety of zagociguat in participants with MELAS who completed TIS6463-203

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tisento Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Decision date (initial)

2025-04-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-517514-15-00

ClinicalTrials.gov

NCT06961344

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Primary Safety: To evaluate the long-term safety and tolerability of zagociguat

Secondary objectives 11

1. To evaluate the long-term effect of zagociguat on safety measurements
2. To evaluate the long-term effect of zagociguat on bone density
3. To evaluate the long-term effect of zagociguat on bone turnover
4. To evaluate the long-term effect of zagociguat on SLE 1
5. To evaluate the long-term effect of zagociguat on disease progression
6. To evaluate the long-term effect of zagociguat on disease pathophysiology
7. To evaluate the long-term effect of zagociguat on clinicians’ impression of disease
8. To evaluate the long-term effect of zagociguat on renal function
9. To evaluate the long-term effect of zagociguat on average blood glucose
10. To evaluate the long-term effect of zagociguat on cardiac function
11. Exploratory phramacokinetics - To assess zagociguat plasma pharmacokinetics

Conditions and MedDRA coding

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)

Regulatory references

Scientific advice from competent authorities

Tisento Therapeutics Inc.

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (ICF) before any study-specific procedures are performed.
2. Completed TIS6463-203 treatment through the Period 2 Week 12 visit
3. If female, meets 1 of the 2 following criteria: a. Confirmed as being postmenopausal (no menses for ≥1 year or ≥12 consecutive months) or surgically sterile (bilateral oophorectomy, hysterectomy, or tubal sterilization [tie, clip, band, or burn]) OR b. If of reproductive potential: • Is not pregnant at the time of the Screening Visit and • Has negative pregnancy test results at the Screening Visit
4. Male and female participants of reproductive potential must agree to use 1 of the following highly effective contraception methods (a or b) from the date of signing the ICF until ≥90 days after receiving their final study drug dose: a. Completely abstain from heterosexual intercourse OR b. If heterosexually active, adhere to ≥1 of the following: • Use a combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, OR intrauterine hormone-releasing system • Have had a bilateral tubal occlusion • Maintain a monogamous relationship with a partner who is permanently sterilized either by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis), hysterectomy, bilateral salpingectomy, or bilateral oophorectomy or is sterile due to postmenopausal status.
5. Female participants on hormone replacement therapy must use ≥1 nonhormonal highly effective contraception methods listed above
6. Male participants must agree to refrain from donating sperm from the Screening Visit through 90 days after their final dose of study drug
7. Female participants must agree to refrain from egg donation through 30 days after the final dose of study drug

Exclusion criteria 4

1. Participants must NOT meet the following exclusion criteria on Day −1 to be enrolled: Met any individual stopping criteria (see Section 5.4.2) while participating in lead-in study TIS6463-203
2. On a reduced dose at the Week 12 visit in either period of lead-in study TIS6463-203
3. Experience a suspected unexpected serious adverse reaction (SUSAR) in lead-in study TIS6463-203
4. Any medical condition or clinical finding that, per investigator judgement, would preclude safe study participation and/or completion of all trial requirements

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment-emergent adverse events (TEAEs)

Secondary endpoints 11

1. Vital sign measurements, ECG assessments, clinical laboratory tests, and C-SSRS responses at each scheduled timepoint
2. DEXA hip and lumbar spine BMD at each scheduled timepoint
3. Concentrations of CTX and P1NP at each scheduled timepoint
4. Incidence of SLE. Time to first SLE from Day 1
5. NMDAS scores at each scheduled timepoint
6. Concentrations of lactate, GDF-15, FGF-21, B2M, serum amyloid P component, TNFR-2, vWF, ICAM-1, NfL, and VCAM-1 at each scheduled timepoint
7. CGI-C overall MELAS scale score at each scheduled timepoint
8. eGFR and UACR at each scheduled timepoint
9. HbA1c level at each scheduled timepoint
10. Concentrations of troponin I, NT-proBNP, and creatine kinase (CK)-MB at each scheduled timepoint
11. Exploratory pharmacokinetics: Concentrations of zagociguat at each scheduled time point

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tisento Therapeutics Inc.

Sponsor organisation

Tisento Therapeutics Inc.

Address

245 1st Street Suite 18

City

Cambridge

Postcode

02142-1292

Country

United States

Scientific contact point

Organisation

Tisento Therapeutics Inc.

Contact name

Clinical Operations

Public contact point

Organisation

Tisento Therapeutics Inc.

Contact name

Clinical Operations

Third parties 7

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications