To study the safety and effectiveness of the maximum tolerated dose of zamicastat, found in BIA-51058-201, in the treatment of long-term PAH.

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2018-002796-18-IT
• Date of registration: 29/01/2021
• Prospective Registration: No
• Primary sponsor: BIAL-Portela & Ca, S.A.
• Public title: To study the safety and effectiveness of the maximum tolerated dose of zamicastat, found in BIA-51058-201, in the treatment of long-term PAH.
• Scientific title: An open-label, multicentre study to evaluate the safety and efficacy of zamicastat as adjunctive therapy in long-term treatment of pulmonary arterial hypertension (PAH) disease - Safety and efficacy of BIA 5-1058 in PAH
• Date of first enrolment: 28/11/2019
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002796-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany, Italy, Portugal, Spain, Ukraine, United Kingdom

Contacts

• Name: Development Department
• Affiliation: Bial - Portela & Ca, S.A.

• Name: Development Department
• Affiliation: Bial - Portela & Ca, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have performed MPV3 of the preceding study BIA-51058-201.
2. Able to comprehend and willing to sign an informed consent form.
3. For women: Agree not to donate ova from the time of informed consent until 30 days after the last IMP intake.
For men: Agree not to donate sperm from the time of informed consent until 90 days after the last IMP intake.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Significant non-compliance with the protocol during the preceding study BIA-51058-201 which may have an impact on this extension study. 2. WHO functional class IV as judged by the investigator. 3. Two or more consecutive measurements of systolic blood pressure (SBP) < 95 mmHg or diastolic blood pressure (DBP) < 50 mmHg, measured at visit V1. 4. Uncontrolled diabetes mellitus with HbA1c = 8.5% within the last three months or at visit V1. 5. Occurrence of an AE during the preceding study which is judged by the investigator as contraindicative to further participation in the extension study. 6. Any disease known to cause pulmonary hypertension other than PAH WHO Group 1. 7. Obstructive lung disease: Forced Expiratory Volume in 1 second/Forced Vital Capacity (FEV1/FVC) < 60% and FEV1 < 60% of predicted value after bronchodilator administration, as demonstrated and documented by previous spirometry data which, in the opinion of the investigator, represent the clinical state of the patient at the time of visit V1. 8. Restrictive lung disease: Total Lung Capacity (TLC) < 70% of predicted value, as demonstrated and documented by previous spirometry data which, in the opinion of the investigator, represent the clinical state of the patient at the time of visit V1. 9. History of moderate to severe hepatic impairment (Child-Pugh B and C). 10. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (measured at MPV1 of study BIA-51058-201). 11. Use of the following prohibited medication or treatments during study participation: calcium channel blockers (CCBs) if used for the treatment of PAH in vasoreactive patients; drugs containing a catechol group that is metabolised by DßH (e.g. rimiterole, isoprenaline, dopamine, dopexamine or dobutamide) or a- and/or ß-blockers. 12. Presence of any other significant or progressive/unstable medical condition that, in the opinion of the investigator, would compromise evaluation of the study treatment or may jeopardise the patient’s safety, compliance or adherence to protocol requirements. 13. For women: Pregnancy or breast-feeding. Women of childbearing potential unable or unwilling to undergo pregnancy tests and practice highly effective contraceptive measures in combination with a barrier method e.g. condom, occlusive cap (diaphragm or cervical/vault caps) with spermicidal gel/film/cream/suppository from the time of informed consent until 30 days after the last IMP intake. Highly effective methods for women are surgical intervention (e.g. bilateral tubal occlusion), non-hormonal implantable intrauterine device, true sexual abstinence (i.e. when this is in line with the preferred and usual lifestyle of the patient) and vasectomised partner (provided that the partner is the sole sexual partner of the patient and the partner has received medical assessment of the surgical success). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), hormonal contraceptives and withdrawal are not acceptable methods of contraception. For men: Male patients who are sexually active with a partner of childbearing potential must use, with their partner, a condom plus an approved acceptable contraceptive measure from the time of informed consent until 90 days after the last IMP intake. The following methods are acceptable methods of contraception: partner’s use of combined (oestrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravag

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary arterial hypertension
MedDRA version: 20.0 Level: SOC Classification code 10038738 Term: Respiratory, thoracic and mediastinal disorders System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: zamicastat
Product Code: [BIA-5-1058]
Pharmaceutical Form: Tablet
INN or Proposed INN: zamicastat
CAS Number: 1080028-80-3
Current Sponsor code: BIA 5-1058
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To assess the safety and tolerability of the individual highest tolerated zamicastat doses, achieved in the study BIA-51058-201, during long-term treatment in PAH disease.

Timepoint(s) of evaluation of this end point: As soon as the last subject has completed the last visit and all data have been locked, the results will be analysed and described in a Clinical Study Report.

Primary end point(s): The safety and tolerability of the used zamicastat doses will be evaluated by:
1. Adverse events
2. Clinically relevant changes in laboratory parameters (haematology, biochemistry,
coagulation, urinalysis, arterial blood gas analysis)
3. Clinically relevant changes in vital signs
4. Clinically relevant changes in ECG parameters
5. Number of digital scars (only in patients with scleroderma)
6. Skin score (only in patients with scleroderma)

Secondary Objective: To assess further efficacy, safety and tolerability parameters of the individual highest tolerated zamicastat doses in long-term treatment of PAH.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: As soon as the last subject has completed the last visit and all data have been locked, the results will be analysed and described in a Clinical Study Report.

Secondary end point(s): Change from baseline* to V5 (if applicable) and from V1 to V5 (if applicable) for the following parameters:
1. Pulmonary vascular resistance (PVR), right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2). Further haemodynamic parameters may also be calculated if considered appropriate.
Change from baseline* to V3 and to V5/EDV and from V1 to V5/EDV for the following parameters:
2. WHO functional class
3. 6-minute walk test (6-MWT), including Borg dyspnoea score
4. Biomarker (N-terminal pro brain natriuretic peptide [NT-proBNP])
5. Echocardiogram parameters:
• Tricuspid regurgitation, classified as absent, mild, moderate or severe
• Right ventricular contractility, measured via tricuspid annular plane systolic
excursion (TAPSE)
• Pericardial effusion, classified as absent, traces or present
• Right atrial area (end-systolic), right ventricular end-diastolic area
6. Quality of life (SF-36v2)

Secondary ID(s)

2018-002796-18-PT

BIA-51058-202

Source(s) of Monetary Support

Bial - Portela & Ca, S.A.

Ethics review

Status: Approved
Approval date: 07/11/2019
Contact: