A PHASE 2A, OPEN-LABEL SINGLE ARM MULTICENTER EXPLORATORY STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF ORAL DOSES OF ROC-101 IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) AND PULMONARY HYPERTENSION ASSOCIATED WITH INTERSTITIAL LUNG DISEASE (ILD-PH)

Trial ID: 2025-522074-37-00
Protocol: ROC-101-201
Sponsor: Allrock Bio Inc.

Trial statistics

science

test molecule

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Pulmonary arterial hypertension

Objectives

The primary objectives of this study are to evaluate the effect of ROC-101 on pulmonary vascular resistance in participants with pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease treated with ROC-101 plus standard of care, and to determine the safety and tolerability of ROC-101 following oral administration. Pulmonary vascular resistance is a critical hemodynamic parameter that directly reflects the degree of vascular remodeling and vasoconstriction in the pulmonary circulation, making it a clinically relevant endpoint for assessing therapeutic efficacy in these conditions.

The secondary objectives include:

• Evaluation of the effect of ROC-101 on 6-minute walk distance in pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease participants treated with ROC-101 plus standard of care

• Assessment of changes in N-terminal pro-B-type natriuretic peptide in pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease participants treated with ROC-101 plus standard of care

• Assessment of changes in World Health Organization Functional Class in pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease participants treated with ROC-101 plus standard of care

• Assessment of changes in other key hemodynamic parameters in pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease participants treated with ROC-101 plus standard of care

Participants

This clinical trial enrolled a total of **19 participants** diagnosed with either **Pulmonary Arterial Hypertension (PAH)** or **Pulmonary Hypertension Associated with Interstitial Lung Disease (ILD-PH)**. The study population included both **male and female** adults aged **18 years and older**. Participants were required to have symptomatic pulmonary hypertension classified as **WHO Functional Class II or III**. The trial population was selected based on specific diagnostic criteria confirmed by **right heart catheterization (RHC)**, with PAH participants demonstrating **pulmonary vascular resistance (PVR)** of at least 5 Wood units and ILD-PH participants showing PVR of at least 3 Wood units. All participants were required to be on stable background therapy for at least 30 days prior to enrollment, with PAH participants receiving at least two approved PAH therapies and ILD-PH participants potentially receiving inhaled treprostinil or **PDE5 inhibitors**. Participants were required to have a **body weight** greater than 50.0 kg and a **body mass index (BMI)** between 19.00 and 36.00 kg/m², inclusive. Physical activity was assessed through **six-minute walk distance (6MWD)** testing, with values required to be between 100 and 550 meters. Participants needed to demonstrate adequate **pulmonary function** based on specific criteria for their diagnosis, including **forced vital capacity (FVC)** and **forced expiratory volume in one second (FEV1)** measurements. The trial included a vulnerable population and required participants to be able to swallow tablets and comply with contraceptive requirements throughout the study period.

Plans and Procedures

This is a Phase 2a, open-label, single-arm, multicenter exploratory study designed to evaluate the safety, tolerability, and efficacy of oral doses of ROC-101 in patients with pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. The study employs an open-label design without randomization or blinding procedures. The investigational medicinal product ROC-101 is administered as a tablet for oral use, containing ROC-101 hydrochloride as the active substance of chemical origin. The maximum daily dose is 40 mg, with a maximum total dose of 57,390 mg administered over a maximum treatment period of 1,440 days.

The primary objectives are to evaluate the effect of ROC-101 on pulmonary vascular resistance in participants with pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease when treated with ROC-101 plus standard of care, and to determine the safety and tolerability of ROC-101 following oral administration. The primary endpoints include the change in pulmonary vascular resistance from baseline versus at 24 weeks, and safety assessments including adverse events, vital signs (body temperature, heart rate, blood pressure, respiratory rate, fraction of inspired oxygen, and saturation of peripheral oxygen), 12-lead electrocardiograms, and safety laboratory tests.

Secondary endpoints encompass the change in 6-minute walk distance from baseline versus at 24 weeks, change in NT-proBNP from baseline versus at 24 weeks, change in WHO functional class from baseline versus at 24 weeks, and changes in various hemodynamic parameters including right atrial pressure, mean pulmonary artery pressure, cardiac output, cardiac index, pulmonary capillary wedge pressure, mixed venous oxygen saturation, stroke volume, stroke volume index, pulse pressure, and pulmonary artery compliance from screening versus at 24 weeks.

The study includes participants aged 18 years or older with documented findings on right heart catheterization consistent with either WHO Group 1 pulmonary arterial hypertension or WHO Group 3 pulmonary hypertension associated with interstitial lung disease. Eligible participants must have symptomatic pulmonary hypertension classified as WHO Functional Class II or III. For pulmonary arterial hypertension participants, right heart catheterization must document pulmonary vascular resistance of at least 5 Wood units, pulmonary capillary wedge pressure of 15 mmHg or less, and mean pulmonary artery pressure greater than 20 mmHg. For pulmonary hypertension associated with interstitial lung disease participants, pulmonary vascular resistance must be at least 3 Wood units, with pulmonary capillary wedge pressure of 15 mmHg or less and mean pulmonary artery pressure greater than 20 mmHg.

Participants may be receiving background therapy for their condition. Pulmonary arterial hypertension participants must be on at least two approved therapies for at least 90 days prior to screening and on a stable dose for at least 30 days prior to Day 1, which may include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and parenteral, inhaled, or oral prostacyclins. Participants receiving sotatercept must have been on a stable dose for at least 6 months prior to Day 1. Participants with pulmonary hypertension associated with interstitial lung disease may receive inhaled treprostinil or phosphodiesterase-5 inhibitors but not other medications used in pulmonary arterial hypertension.

Additional inclusion criteria include pulmonary function tests meeting specified thresholds, acceptable electrocardiogram findings with normal sinus rhythm, corrected QT interval of 450 msec or less for males and 460 msec or less for females, and QRS interval of 120 msec or less. Body weight at screening and baseline must be greater than 50.0 kg, with body mass index ranging from 19.00 to 36.00 kg/m². The 6-minute walk distance must be between 100 and 550 meters, repeated twice during the screening period and at the baseline visit, with both values within 15% of each other. Pulmonary arterial hypertension participants require a ventilation-perfusion scan or negative CT pulmonary angiogram with normal or low probability results that are not clinically significant.

The screening period includes a right heart catheterization performed within 2 weeks of or during screening and prior to baseline to confirm eligibility. The baseline visit occurs on Day 1, when study drug administration begins. The main study period is defined as completion of assessments through the Week 24 visit. An extension period is available for participants who complete the main study period, with continuation of treatment and assessments. Participants in the extension period must have negative pregnancy tests if they are women of childbearing potential and must comply with contraceptive guidance until 28 days after the last dose of study drug for women of childbearing potential and 90 days after the last dose for males.

The estimated recruitment start date is February 2, 2026, with an estimated end date of March 4, 2029. The total estimated duration of participant involvement in the main study is 24 weeks, with the possibility of extended participation in the long-term extension period. Conditions that may lead to early termination from the study are not explicitly specified in the available information. Throughout the study, participants are required to communicate effectively with investigators, understand study procedures, and complete the study in accordance with the protocol. Participants must be able to swallow tablets and must agree to ongoing pregnancy testing and contraceptive measures as outlined in the study protocol.

Treatment

The experimental treatment under investigation is **ROC-101**, which contains the active substance **roc-101 hydrochloride** of chemical origin. ROC-101 is formulated as an oral **tablet** and is administered via **oral use**. The maximum daily dose is **40 mg**, with a maximum total dose of **57390 mg** over a treatment period of up to **1440 days**. The investigational medicinal product is manufactured by ALLROCK BIO, INC. and is designated with the sponsor product code ROC-101. This product is classified as a test medicinal product and is not a paediatric formulation.

Participants in this clinical trial will receive ROC-101 in combination with **standard of care** therapy for their underlying condition. The study evaluates the effect of ROC-101 when administered as an add-on treatment to existing standard therapeutic regimens for **pulmonary arterial hypertension** and **pulmonary hypertension associated with interstitial lung disease**. The trial design incorporates the continued use of standard of care medications throughout the study period to assess the safety, tolerability, and efficacy of the experimental treatment in conjunction with established therapeutic approaches.

Efficacy

Efficacy will be assessed through multiple parameters measured at defined timepoints throughout the study. The primary efficacy endpoint is the change in **pulmonary vascular resistance** (PVR) from Baseline versus at 24 weeks. Secondary efficacy endpoints include the change in **6-minute walk distance** (6MWD) from Baseline versus at 24 weeks, the change in **NT-proBNP** from Baseline versus at 24 weeks, and the change in **WHO Functional Class** (WHO FC) from Baseline versus at 24 weeks. Additional hemodynamic parameters will be evaluated, including changes in **right atrial pressure** (RAP), **mean pulmonary artery pressure** (mPAP), **cardiac output** (CO), **cardiac index** (CI), **pulmonary capillary wedge pressure** (PCWP), **mixed venous oxygen saturation** (SvO2), **stroke volume** (SV), **stroke volume index** (SVI), **pulse pressure** (PP), and **pulmonary artery compliance** (PAC) from Screening versus at 24 weeks. Hemodynamic assessments will be conducted using **right heart catheterization** (RHC) performed during the Screening period and at 24 weeks. The 6MWD will be measured at Baseline and at 24 weeks. Safety assessments will be conducted throughout the study and include monitoring of adverse events, vital signs (body temperature, heart rate, blood pressure, respiratory rate, fraction of inspired oxygen, and saturation of peripheral oxygen), **12-lead electrocardiograms** (ECG), and safety laboratory tests.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Must be age 18 or older at the time of signing the informed consent form (ICF). The participant must understand and voluntarily sign an ICF prior to any study-related procedures.
Documented findings on a right heart catheterization (RHC) consistent with a diagnosis of EITHER: WHO Group 1 PAH of any of the following subtypes: i. Idiopathic PAH ii. Heritable PAH iii. Drug- or toxin-induced PAH (having been in the care of the Investigator for at least 1 year with no relapses of drug or toxin/chemical abuse) iv. PAH associated with connective tissue disease (CTD) v. PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair AND have no, or clinically insignificant, shunt fraction in the opinion of Investigator [1.0 ≤ pulmonary-systemic flow ratio ≤ 1.5]. OR WHO Group 3 ILD-PH of any of the following subtypes: i. PH diagnosis confirmed on RHC and ii. ILD diagnosis based on more than 10% pulmonary fibrosis on HRCT imaging and PFTs. ILD World Health Organization (WHO) Group 3 PH may include one of the following: a. Idiopathic interstitial pneumonia including: i. Idiopathic pulmonary fibrosis ii. Idiopathic nonspecific interstitial pneumonia iii. Respiratory bronchiolitis-associated interstitial lung disease iv. Desquamative interstitial pneumonia v. Cryptogenic organizing pneumonia vi. Acute interstitial pneumonitis vii. Idiopathic lymphoid interstitial pneumonia viii. Unclassifiable idiopathic interstitial pneumonia b. Chronic hypersensitivity pneumonitis c. Occupational lung disease (drug or radiation-induced)
Symptomatic PH classified as WHO Functional Class II or III symptoms
RHC (performed within 2 weeks of or during Screening period and prior to the Baseline to confirm eligibility) documenting the following: a. PAH participants enrolled in Cohorts 1 or 2: PVR of ≥ 5 Wood units, PCWP ≤ 15 mmHg and mPAP > 20 mm Hg. b. ILD-PH participants enrolled in Cohort 3: PVR of ≥ 3 Wood units, PCWP ≤ 15 mmHg and mPAP > 20 mm Hg (and enrollment of participants with PVR up to 4 Wood units capped at n=5, and the remaining 5 participants must have PVR >4 Wood units).
Participants may be on background therapy for PAH or ILD-PH: a. PAH participants must be on a background of at least two approved PAH therapies for at least 90 days prior to Screening and a stable dose for at least 30 days prior to Day 1: i. ERA, ii. PDE5i, iii. sGC stimulators, iv. Parenteral, inhaled, and PO prostacyclins (including prostanoids and prostacyclin receptor agonists). Stability of parenteral prostacyclins means a change of no more than 15% in the previous 30 days from the start of Screening. b. Participants who are receiving sotatercept (only allowed in Cohort 2) must have been on a stable dose for at least 6 months prior to Day 1. c. Participants in Cohort 3 (ILD-PH) may be receiving doses of inhaled treprostinil and/or PDE5i (for at least 90 days prior to Screening and a stable dose for at least 30 days prior to Day 1), but not other medications that could be used in PAH such as ERAs, sGC stimulators, enteral or parenteral prostacyclins or sotatercept.
Females of childbearing potential (as defined in protocol) must: a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting the study drug and must agree to ongoing pregnancy testing during the course of the study as outlined in the schedule of assessments (SOA). b. If sexually active, agree to use highly effective contraception (as defined in the protocol) without interruption, for at least 28 days prior to starting the study drug, during the study (including dose interruptions and longterm extension period), and for 4 weeks (28 days) after discontinuation of study drug. c. Refrain from breastfeeding a child or donation of ovum for the duration of the study and for at least 28 days after the last dose of study drug.
Male participants must have had a vasectomy with confirmed azoospermia at least 120 days prior to screening. Vasectomized males must also agree to use effective barrier contraception during the study (including the longterm extension period) and for at least 90 days following the last administration of the study drug. Male participants must follow protocol-specified contraception guidance.
Participants must be able to communicate well with Investigators, understand the study procedures in the ICF and are agreeable to complete the study in accordance with the protocol.
Must be able to swallow tablets.
Pulmonary function tests: PAH participants at Screening as follows: a. FVC > 70% predicted; or if between 60% to 70% predicted, or if not possible to be determined, confirmatory HRCT indicating no more than mild (<10% fibrosis) ILD and emphysema (less than 10%); and b. The ratio of FEV1 (first second)/FVC > 0.70 of predicted. ILD-PH participants at Screening as follows: a. PFTs consistent with their ILD diagnosis and showing FEV1/ FVC ratio > 65% and HRCT having more than 10% fibrosis and less than 10% emphysema, based on the proportion of lung parenchyma affected by fibrotic and emphysema changes. and, b. Minimum FVC of 50% and DLCO (corrected for Hb g/dl) >25%
In PAH participants, i.e., Cohorts 1 and 2 only, ventilation-perfusion (VQ) scan (or, if unavailable, a negative CT pulmonary angiogram [CTPA] or pulmonary angiography result), any time prior to Screening or conducted during the Screening Period, with a normal or low probability result that is not clinically significant.
Acceptable ECG findings as assessed by the Investigator or qualified designee at the Screening Visit and at the Baseline Visit (Day 1), including each criterion as listed below: • Normal sinus rhythm (HR) between 40 and 100 beats per minute, inclusive); • Corrected QT Interval (QTcF) interval ≤ 450 msec (males) and ≤ 460 msec (females); • QRS interval ≤ 120 msec; if > 120 msec, result will be confirmed by a manual over read.
Body weight at the Screening visit and at Baseline (Day 1) is greater than 50.0 kg and the body mass index (BMI) is in the range of 19.00 to 36.00 kg/m2, inclusive.
6MWD ≥ 100 and ≤ 550 meters repeated twice, once during Screening Period and once at the Baseline Visit (Day 1) and both values within 15% of each other, allowing for a third repeat if > 15% difference, calculated from the higher/highest value.
Extension Period: 1. Participants must complete the main study period (defined as completion of assessments through the Week 24 visit).
Extension Period: 2.Women of child-bearing potential (WOCBP) must have negative pregnancy test.
Extension Period: 3. All participants must comply with contraceptive guidance until 28 days after last dose of study drug for WOCBP and 90 days after the last dose of study drug for males.

cancel

Exclusion Criteria

Diagnosis of PH WHO Groups 2, 4, or 5
Pregnant or breastfeeding females.
Uncontrolled systemic hypertension as evidenced by sitting SBP > 160 mm Hg or sitting diastolic BP > 100 mm Hg during Screening Visit and Baseline Visit (Day 1) after a period of rest.
Systolic BP < 90 mm Hg during Screening Visit or at Baseline Visit (Day 1).
History of known pericardial constriction or a clinically significant (more than trace or trivial [i.e., ≥10 mm]) pericardial effusion seen in diastole or in both systole and diastole on ECHO historically and confirmed on screening ECHO.
RHC contraindicated during the study per Investigator.
Cerebrovascular accident within 3 months (120 days) of start of Screening.
History of restrictive or constrictive or congestive cardiomyopathy.
Left ventricular ejection fraction (LVEF) < 50% on historical echocardiogram (ECHO) performed within 6 months prior to start of Screening period (and confirmed during the Screening ECHO) or grade 2 or higher diastolic dysfunction .
Any current symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain in the past 6 months (180 days) prior to start of Screening).
History of acutely decompensated left heart failure or right heart failure within 90 days prior to Baseline, as per Investigator assessment.
Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH, PAH associated with portal hypertension, schistosomiasis-associated PAH and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis.
Significant (≥ 2+ [or > mild] regurgitation) mitral regurgitation or aortic regurgitation valvular disease, or more than mild mitral stenosis or aortic stenosis valvular disease as seen on Screening ECHO.
Started or stopped receiving any general supportive therapy for PH (e.g., oxygen, anticoagulants, digoxin) within 30 days prior to start of Screening.
Use of supplemental oxygen > 10 liters/minute and SpO2 < 90% while receiving typical oxygen supplementation.
Received intravenous (IV) inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to start of Screening.
History of atrial septostomy within 180 days prior to start of Screening.
History of portal hypertension or chronic liver disease, defined as mild to severe hepatic impairment (Child-Pugh Classes A to C).
Untreated, severe (defined as apnea hypoxia index of > 30) obstructive sleep apnea.
Active daily smoker of cannabis or tobacco.
Current alcohol abuse or current illicit drug use.
WHO Group 3 due to severe chronic obstructive pulmonary disease (COPD) or chronic pulmonary fibrosis and emphysema (CPFE) or PFT with FVC < 50% or FEV1/FVC < 65% or DLCO < 25% (corrected for Hb g/dl).
Positive blood test for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody (HCVAb) (unless participants have had treatment for HCV and have a negative HCV ribonucleic acid [RNA] polymerase chain reaction [PCR]) or HIV antibody.
Presence of lab abnormalities at Screening: • Liver function tests: alanine transaminase (ALT) or aspartate transaminase (AST) >2X upper limit of normal [ULN] and total bilirubin >1.5X ULN. • Estimated creatinine clearance <60 mL/min • Hemoglobin < 9 g/dL for Cohort 1 and Cohort 3; Hemoglobin < 9 g/dL or > 16 g/dL for Cohort 2 • Absolute neutrophil count < 1500/mm3 • Platelets < 100,000/μL • White blood cell (WBC) count < 4000/mm3
History of greater than severe renal disease, including any episode of acute renal failure, with or without a prior history of renal disease in which acute dialysis (e.g., intermittent hemodialysis or continuous veno-venous hemofiltration) was required.
Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Baseline or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible).
Participants who plan to continue, or start during the study, medications which are sensitive cytochrome (CYP) 2D6 substrates with a narrow therapeutic index, such as nortriptyline, venlafaxine, and amitriptyline or CYP1A2 substrates with a narrow therapeutic index. See Appendix 3 for a more inclusive listing of such medications.
History or presence of impaired cardiac function including but not limited to: • Risk factors for Torsade de Pointes (e.g., left heart failure, cardiomyopathy, or family history of either Long QT Syndrome or sudden unexpected cardiac death at a young age) • Sick sinus syndrome, second- or third-degree atrioventricular block, pulmonary congestion, symptomatic or significant cardiac arrhythmia, or other clinically significant conduction abnormalities, e.g., left bundle branch block. • Ischemic heart disease, symptomatic arrhythmias, or poorly controlled hypertension. • Conditions predisposing to QT prolongation including pathological Q-wave, or concomitant medications known to prolong QTc (see Appendix 3 for a listing of examples of such medications).
Participants who plan to donate blood after signing consent for the study and for 28 days after their last dose of study drug.
Extension Period: 1. Participant withdrew from main study period due to an AE related to study drug,
Extension Period: 2. Female participant who is pregnant, breastfeeding, or intends to conceive during the long-term extension period.
Extension Period: 3. Any condition that in the opinion of the investigator may pose a risk to the participant, interferes with the participant’s participation or confounds assessments of the participant.
Participants with known hypersensitivity to ROC-101 or any components of its formulations.
History of malignancy within the last 5 years, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin.
History of clinically significant (as determined by the Investigator) non-PAH related cardiac, endocrine, hematologic, hepatic, immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or other diseases that may limit participation in the study.
Participation in another clinical trial involving intervention with another investigational drug, approved therapy for investigational use, or investigational device within 4 weeks prior to Baseline Visit (unless it is in the follow-up period of an interventional study), or if the half-life of the previous product is known, within 5× the half-life prior to Baseline Visit (Day 1), whichever is longer.
Major surgery within 8 weeks prior to Baseline Visit (Day 1) or major surgery scheduled or planned in the main study. Participants must have completely recovered from any previous surgery prior to the Screening Visit.
Prior heart or heart-lung transplants, or a participant listed for heart and/or lung transplantation or prior pneumonectomy.
Nonvasectomized males, males who plan to undergo vasectomy reversal procedures, or vasectomized males who will not wear barrier contraception.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Recruiting	02 Feb 2026	2
Germany	Recruiting	02 Feb 2026	2
Italy	Recruiting	02 Feb 2026	6
Latvia	Recruiting	02 Feb 2026	4
Poland	Not Yet Recruiting	02 Feb 2026	3
Spain	Recruiting	02 Feb 2026	4