Sotatercept for Pulmonary Arterial Hypertension

(SOTERIA Trial)

Not currently recruiting at 305 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Acceleron Pharma Inc.

Must be taking: PAH therapy

Disqualifiers: Pregnancy, Breastfeeding, Missed doses, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 50 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of sotatercept for individuals with Pulmonary Arterial Hypertension (PAH), a condition characterized by high blood pressure in the lung arteries. It targets participants who have previously participated in a sotatercept study, focusing on their long-term tolerance of the treatment. Sotatercept will be added to their existing PAH regimen to assess its continued benefits. Ideal candidates for this trial are those with PAH who completed a previous sotatercept study without major interruptions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications. It mentions that sotatercept is added to existing PAH therapy, so you may continue your current PAH treatments.

Is there any evidence suggesting that sotatercept is likely to be safe for humans?

Research shows that sotatercept is generally safe for people with Pulmonary Arterial Hypertension (PAH). In earlier studies, patients who took sotatercept experienced improved blood flow and heart function. These studies also assessed how well participants tolerated sotatercept, with most experiencing no serious side effects. An independent safety committee reviewed the data and found no major safety issues.

Early results from a follow-up study further support the safety of sotatercept when combined with other PAH treatments. While any treatment carries some risks, the data suggests that most people tolerate sotatercept well, making it a promising option for those with PAH. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PAH?

Most treatments for pulmonary arterial hypertension (PAH) focus on dilating blood vessels to improve blood flow, like endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogs. Sotatercept, however, works differently by targeting the transforming growth factor-beta (TGF-β) superfamily, which plays a role in vascular remodeling. This unique mechanism can potentially reverse the damaging changes in blood vessels associated with PAH, rather than just managing symptoms. Researchers are excited about sotatercept because it offers a novel approach that could lead to significant improvements in long-term outcomes for patients with PAH.

What evidence suggests that sotatercept might be an effective treatment for Pulmonary Arterial Hypertension?

Research shows that sotatercept, the treatment under study in this trial, may help treat pulmonary arterial hypertension (PAH). In earlier studies, patients taking sotatercept showed improved heart function and increased physical activity. One study found that sotatercept reduced the risk of worsening health problems by 76% compared to a placebo. Additionally, long-term studies have demonstrated that the benefits of sotatercept outweigh the risks for patients. These results suggest that sotatercept could effectively manage PAH symptoms. ^{2 5 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with Pulmonary Arterial Hypertension who've completed previous sotatercept studies without early discontinuation. Participants must agree to contraception and not donate blood or sperm. They can't join if they missed more than 4 doses between studies, have ongoing serious side effects from prior sotatercept trials, or are pregnant/breastfeeding.

Inclusion Criteria

I use and will continue to use effective birth control and a barrier method during the study.

I agree not to breastfeed or donate eggs/blood for 16 weeks after the last study drug dose.

I agree to use specified condoms during the study and for 16 weeks after, even if I've had a vasectomy.

Exclusion Criteria

I am experiencing a serious side effect from a PAH drug study possibly due to sotatercept.

Pregnant or breastfeeding females

Did not participate in a sotatercept PAH parent trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sotatercept at a dose of 0.3 mg/kg SC initially, escalating to 0.7 mg/kg SC for the remainder of the study

Up to approximately 50 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 48 months

Open-label extension

Participants continue to receive sotatercept to evaluate long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Sotatercept

Trial Overview The study tests the long-term safety and effectiveness of a drug called Sotatercept in patients with PAH when added to their current treatment regimen. It's an open-label follow-up to earlier phases where Sotatercept showed promise in improving heart and lung function.

How Is the Trial Designed?

Group I: Sotatercept Treatment Experimental Treatment 1 Intervention

Participants rolling over from a blinded parent study will begin sotatercept at a dose of 0.3 mg/kg subcutaneous (SC) injection for Visit 1. Dose will escalate to 0.7 mg/kg SC injection at Visit 2 through the remainder of the study. Participants rolling over from an unblinded parent study will continue sotatercept at their current dose and, if at a dose \<0.7 mg/kg SC injection, can titrate up to 0.7 mg/kg SC injection for the remainder of the study.

Who Is Running the Clinical Trial?

Acceleron Pharma Inc.

Lead Sponsor

Trials

27

Recruited

3,100+

Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Lead Sponsor

Trials

33

Recruited

4,300+

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Lead Sponsor

Trials

33

Recruited

4,300+

Published Research Related to This Trial

The Phase 3 STELLAR trial demonstrated that sotatercept significantly improves exercise capacity and reduces pulmonary vascular resistance in patients with pulmonary arterial hypertension, indicating its efficacy as a treatment option.

The study involved a large cohort of patients, providing robust evidence for the safety and effectiveness of sotatercept in managing this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In symptomatic PAH, adding sotatercept to stable background therapy improved 6-min walk distance at 24 wk. Estrada, RA.[2023]

In a phase 3 trial involving 323 adults with pulmonary arterial hypertension, sotatercept significantly improved exercise capacity, as measured by a 34.4 m increase in the 6-minute walk distance compared to just 1.0 m in the placebo group, indicating its efficacy in enhancing physical performance.

Sotatercept also showed significant improvements across multiple secondary endpoints related to pulmonary health, although it was associated with some adverse effects like epistaxis and increased blood pressure, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. Hoeper, MM., Badesch, DB., Ghofrani, HA., et al.[2023]

In a study involving 106 participants with pulmonary arterial hypertension, sotatercept demonstrated significant long-term efficacy in reducing pulmonary vascular resistance and improving functional outcomes over 24 months, with sustained benefits observed in both groups receiving sotatercept.

The treatment was generally safe, with serious adverse events occurring in 30.8% of participants, but only a small number (2.9%) of deaths were reported, none linked to the drug, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Humbert, M., McLaughlin, V., Gibbs, JSR., et al.[2023]

The phase 3 STELLAR trial indicated that adding sotatercept to background therapy for pulmonary arterial hypertension (PAH) significantly increases life expectancy, with an estimated gain of 11.5 years per patient compared to background therapy alone.

Sotatercept also reduces the need for infused prostacyclin treatments, hospitalizations due to PAH, and the number of lung/heart-lung transplants required, suggesting it may improve overall patient management in PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH). McLaughlin, V., Alsumali, A., Liu, R., et al.[2023]

In a 24-week trial involving 106 adults with pulmonary arterial hypertension, sotatercept significantly reduced pulmonary vascular resistance compared to placebo, indicating its efficacy in improving this condition.

Sotatercept also improved exercise capacity, as shown by a greater increase in 6-minute walk distance in the treatment groups, although some hematologic adverse events were noted, including thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotatercept for the Treatment of Pulmonary Arterial Hypertension. Humbert, M., McLaughlin, V., Gibbs, JSR., et al.[2021]

Citations

1. merck.com merck.com/news/winrevair-sotatercept-csrk-reduced-the-risk-of-clinical-worsening-events-by-76-compared-to-placebo-in-patients-recently-diagnosed-with-pah-on-background-therapy-in-phase-3-hyperion-trial/

WINREVAIR™ (sotatercept-csrk) Reduced the Risk of ... Results showed the benefits of early initiation of WINREVAIR within the first year after PAH diagnosis. HYPERION results were presented ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2213558

Phase 3 Trial of Sotatercept for Treatment of Pulmonary ... An independent data and safety monitoring committee reviewed unblinded safety data collected 21 days after administration of the first dose of sotatercept or ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39978862/

A long-term follow-up study of sotatercept for treatment ... Interim results of SOTERIA support the favourable benefit-risk of add-on sotatercept treatment in adults with PAH. Follow-up reports from ...

4. winrevair.com winrevair.com/clinical-trials-results/

Clinical Trial Results for WINREVAIR™ (sotatercept-csrk) WINREVAIR™ (sotatercept-csrk) was studied in the 6-month STELLAR clinical study. Patients can view clinical trial results for WINREVAIR.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03496207

NCT03496207 | A Study of Sotatercept for the Treatment ... Study A011-09 is designed to assesses the efficacy and safety of sotatercept (ACE-011) relative to placebo in adults with pulmonary arterial hypertension (PAH).

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40876858/

A New Frontier in Pulmonary Arterial Hypertension Treatment Data synthesis: The findings from this review indicate that sotatercept is an overall safe and effective option for improving PAH outcomes when ...

7. merck.com merck.com/news/u-s-fda-approves-updated-indication-for-winrevair-sotatercept-csrk-in-adults-with-pulmonary-arterial-hypertension-pah-who-group-1-pulmonary-hypertension-based-on-phase-3-zenith-study/

U.S. FDA Approves Updated Indication for WINREVAIR ... “For patients with PAH, the risk of serious events such as hospitalization, transplantation or death remains unacceptably high despite being ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04796337

Study Details | NCT04796337 | A Long ... The primary objective of this open-label, LTFU study is to evaluate the long-term safety and tolerability of sotatercept when added to background PAH therapy in ...