Effect of CS1 in Subjects With Pulmonary Arterial Hypertension

NCT05224531 | Completed Phase 2 FDA Drug

• 1 other identifier: CS1-003
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, parallel group study to evaluate the safety, tolerability, PK, and exploratory efficacy of 3 doses of CS1 in the treatment of PAH using the CardioMEMS HF System to obtain repeated measurements of PAP and other hemodynamic parameters. Elegible subjects will have a RHC to implant the CardioMEMS pulmonary artery (PA) Sensor followed by a Baseline Period for the subject to become familiar with the system, its measurements, how to send the data, and establish Baseline PA pressure. Alternately, the subject may already have the CardioMEMS HF System and is willing to have the system recalibrated in conjunction with RHC. Thereafter, the subject will be randomly assigned to 1 of 3 total daily doses of CS1 1:1:1; there will be 10 subjects assigned to each dose level. Subjects will receive study drug treatment for 12 weeks. During the study, mPAP and other hemodynamic parameters from CardioMEMS PA Sensor will be measured and data captured once daily in the morning before the subject gets out of bed. The data will be transferred electronically to a repository. The analysis will look at the area under the curve (AUC) of mPAP and the doses will be compared to each other regarding change from Baseline. In addition to the CardioMEMS HF System measurements, the subjects will be followed for mortality and morbidity, important biomarkers as well as subjective, functional, and structural parameters of importance for PAH, for the duration of the study. Subjects will be enrolled for up to 22 weeks: a Screening Period of up to 2 weeks prior to the start of the Baseline Period, a Baseline Period of up to 6 weeks prior to Randomization, a Treatment Period of 12 weeks, and a Follow-up Period of 2 weeks. The primary objective of the study is to obtain safety and tolerability data.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension; CARDIOMEMS

Outcome Measures

Primary Outcomes (1)

• Patient reported adverse events

  Safety and tolerability of 3 doses of CS1

  6 months

Study Arms (3)

CS1 480 mg dose group

EXPERIMENTAL

480 mg of CS1, twice daily administration with 1/3 of the dose in the morning and 2/3 in the evening.

Drug: CS1 Administration

CS1 960 mg dose group

EXPERIMENTAL

960 mg of CS1, twice daily administration with 1/3 of the dose in the morning and 2/3 in the evening.

Drug: CS1 Administration

CS1 1920 mg dose group

EXPERIMENTAL

1920 mg of CS1, twice daily administration with 1/3 of the dose in the morning and 2/3 in the evening.

Drug: CS1 Administration

Interventions

CS1 Administration DRUG

CS1 delayed-release capsules will be supplied with 160 mg active pharmaceutical ingredient (sodium valproate) per capsule. Three dose levels that will be evaluated in this study; study drug will be administered as uneven, divided doses twice daily in the morning and in the evening (1/3 of the daily dose is to be administered between 7 and 9 am; 2/3 of the daily dose is to be administered between 7 and 9 pm).

CS1 1920 mg dose group; CS1 480 mg dose group; CS1 960 mg dose group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be willing and able to sign a written informed consent prior to any study-related procedures and able to understand and follow instructions; return to the study unit for specified study visits; and able to participate in the study for the entire period.
• Subject is male or female, aged 18 to 80 years.
• Subject must have a body mass index (BMI) 18 to 40 kg/m2 at Screening. If BMI is \>35 kg/m2, subject chest circumference should be \<65 inches (165 cm).
• Subject with PAH belonging to 1 of the following subgroups of NICE Clinical Classification of PAH category:
• Idiopathic PAH.
• Heritable PAH.
• Drug or toxin-induced (anorexigen or methamphetamine use).
• PAH associated with connective tissue disease.
• Subject with PAH who are symptomatic and have reduced exercise capacity due primarily to their PAH diagnosis, having been assessed by qualified individual, ie, physician, physician assistant, or nurse practitioner, to be in NYHA/WHO functional class II or III and having an RRS 2.0 of 6 to 10.
• PAH therapy at stable doses of standard-of-care therapies for at least 90 days prior to screening.
• Subject has most recent (within the last 36 months) hemodynamic assessment of PAH by RHC demonstrating a persistent resting mPAP ≥25 mm Hg and resting mean pulmonary vascular resistance (PVR) ≥5 Wood Units with Pulmonary Capillary Wedge Pressure ≤15 mmHg.
• Subject is willing to undergo CardioMEMS PA Sensor implantation and RHC prior to randomization or has had the CardioMEMS PA Sensor implanted previously.
• Subject has a 6-minute walk distance (6MWD) ≥150 meters (m) and \<550 m at Screening.
• Female subject of childbearing potential must be willing and able to practice effective contraception during the study and continuing contraception for 30 days after their last dose of study drug. A female subject of non-childbearing potential is defined as being surgically sterilized by bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. A female subject 45 to 60 years of age, who is post-menopausal for at least 1 year, and has a follicle-stimulating hormone level confirmation indicating post menopausal status will be considered of non-childbearing potential. A female subject \>60 years of age is considered post menopausal and of non childbearing potential.

You may not qualify if:

• Subjects will be excluded from the study if they meet any of the following criteria:
• Subject has pulmonary hypertension category 2 to 5.
• Subject has adult congenital heart disease (ACHD).
• Subject has concomitant medical or psychiatric disorder, condition, history, or any other condition that in the opinion of the Investigator would either put the subject at risk or impair the subject's ability to participate in or complete the requirements of the study or confound the objectives of the study.
• Subject has a concomitant medical disorder that is expected to limit the subject's life-expectancy to ≤1 year.
• Subject has RRS 2.0 score of ≤5 or ≥11.
• Subject has heart fai
• lure with preserved ejection fraction defined as those with \>50% ejection fraction (with signs and symptoms of heart failure) or left atrial volume (LAV) \>34 mL/ m2.
• Subject is not able to have CardioMEMS PA Sensor implanted due to:
• An active, ongoing infection defined as being febrile, an elevated white blood cell count, on intravenous antibiotics, and/or positive cultures (blood, sputum, or urine).
• History of current or recurrent (≥2 episodes within 5 years prior to consent) pulmonary emboli and/or deep vein thromboses.
• Cannot tolerate RHC.
• PA branch inner diameter \<7 mm in a descending branch within the left or right lower lung lobe (target implant vessel).
• Unable to take dual antiplatelet or anticoagulation therapy for 1 month after CardioMEMS PA Sensor implantation.
• Subject is likely to undergo lung transplantation within the next 6 months.

Sponsors & Collaborators

• Cereno Scientific AB: lead
• Worldwide Clinical Trials: collaborator

Study Sites (1)

Fredrik Frick

Gothenburg, Sweden

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded Endpoint
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 4, 2022
• Study Start: May 5, 2022
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: October 4, 2024

Record last verified: 2024-10

Locations

SE (1)