A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH)

Key Inclusion Criteria:

1. Signed informed consent by the parent(s) or legally designated representative and
assent from developmentally capable children prior to initiation of any study-mandated
procedure.

2. Males or females between ≥ 2 years and < 18 years of age.

3. Subjects with body weight ≥ 10 kg at randomization.

4. Pulmonary arterial hypertension (PAH) diagnosis, confirmed by historical right heart
catheterization (mPAP ≥ 25 mmHg, and PAWP ≤ 15 mmHg, and PVRi > 3 WUxm2).

5. PAH belonging to the Nice 2013 Updated Classification Group 1 (including subjects with
Down syndrome) and of following etiologies:

- idiopathic PAH

- heritable PAH

- PAH associated with congenital heart disease (CHD)

- Drug or toxin induced PAH

- PAH associated with HIV

- PAH associated with connective tissue diseases (PAH-aCTD)

6. WHO Functional class I to III.

7. Females of childbearing potential must have a negative pregnancy test at Screening and
at Baseline, and must agree to undertake monthly pregnancy tests, and to use a
reliable method of contraception (if sexually active) up to the end of study (EOS).

Key Exclusion Criteria:

1. Subjects with PAH due to portal hypertension, schistosomiasis, or with pulmonary
veno-occlusive disease and/or pulmonary capillary hemangiomatosis, and persistent
pulmonary hypertension of the newborn.

2. Subjects with PAH associated with Eisenmenger syndrome, or with moderate to large
left-to-right shunts.

3. Subjects receiving a combination of > 2 PAH-specific treatments at randomization.

4. Treatment with i.v. or s.c. prostanoids within 4 weeks before randomization, unless
given for vasoreactivity testing.

5. Hemoglobin or hematocrit <75% of the lower limit of normal range

6. Serum AST and/or ALT > 3 times the upper limit of normal range'

7. Pregnancy (including family planning) or breastfeeding.

8. Any circumstances or conditions, which, in the opinion of the investigator, may affect
full participation in the study or compliance with the protocol.