PF-07868489 for Pulmonary Hypertension

Recruiting at 13 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pfizer

Must be taking: PAH vasodilators

Disqualifiers: Smoking, Major surgery, Allergic reactions, others

Compensation: Varies

Number of Visits: 7

90 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires participants with pulmonary arterial hypertension to be on a stable dose of their current PAH medications. The protocol does not specify if other medications need to be stopped.

What data supports the effectiveness of the drug PF-07868489 for pulmonary hypertension?

The research mentions that ambrisentan, a drug used in combination therapy for pulmonary arterial hypertension (PAH), has shown benefits in reducing clinical failure events and improving patient outcomes. This suggests that similar drugs might be effective for pulmonary hypertension. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new medicine called PF-07868489. It aims to see how safe it is and how it behaves in both healthy adults and those with pulmonary arterial hypertension (PAH). The study will help understand how the medicine moves through the body and its effects.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for healthy adults and those with pulmonary arterial hypertension (PAH), a type of high blood pressure affecting the lungs. Participants should have a BMI between 16 to 32 kg/m2 and weigh over 50 kg. It's not clear who can't join because the exclusion criteria are missing.

Inclusion Criteria

My BMI is between 16 and 32, and I weigh more than 50 kg.

Completely healthy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Single Ascending Dose

An investigator- and participant-blind, sponsor-open, placebo-controlled, single ascending dose study to assess the safety, tolerability, and pharmacokinetics (PK) of PF-07868489 in healthy adult participants.

1 week

1 visit (in-person)

Part B: Repeat Doses

A 24-week, randomized, double blind, placebo-controlled study to assess the safety, tolerability, PK, and pharmacodynamics (PD) of PF-07868489 in adult participants with PAH.

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PF-07868489
• Placebo for PF-07868489

Trial Overview The study tests PF-07868489, which could potentially treat PAH. Part A involves giving healthy volunteers either this medicine or a placebo in increasing doses to check safety and how the body processes it. Part B gives PAH patients the drug or placebo for 24 weeks to assess safety and effectiveness.

Participant Groups

Group I: PF-07868489 Experimental Treatment 1 Intervention

single subcutaneous injection (Part A); 6 subcutaneous injections at regular intervals (Part B)

Group II: Placebo Placebo Group 1 Intervention

single subcutaneous injection (Part A); 6 subcutaneous injections at regular intervals (Part B)

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

In a study of 500 participants with pulmonary arterial hypertension (PAH), initial combination therapy with ambrisentan and tadalafil significantly reduced the risk of clinical failure events by 79% for patients with functional class II symptoms and by 42% for those with functional class III symptoms.

The combination therapy also notably decreased hospitalizations for worsening PAH, with no hospitalizations observed in functional class II patients receiving the combination treatment, suggesting that this approach is beneficial even for patients with less severe symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension. White, RJ., Vonk-Noordegraaf, A., Rosenkranz, S., et al.[2020]

The CAMPHOR questionnaire demonstrated better psychometric properties than the SF-36 in assessing patient-reported outcomes in individuals with pulmonary hypertension, based on a study of 65 participants.

CAMPHOR showed good reliability and the ability to distinguish between different World Health Organization functional classes, while the SF-36 had poor test-retest reliability and high ceiling effects in several domains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension. Twiss, J., McKenna, S., Ganderton, L., et al.[2022]

A multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy of ambrisentan in patients with inoperable chronic thromboembolic pulmonary hypertension, but the study was terminated early due to futility of enrollment.

Despite early termination, there were trends indicating that ambrisentan may improve primary and some secondary endpoints compared to placebo, with similar adverse event profiles between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ambrisentan for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Escribano-Subias, P., Bendjenana, H., Curtis, PS., et al.[2020]

In a 24-week study involving 83 Chinese patients with pulmonary arterial hypertension (PAH), treatment with ambrisentan significantly improved exercise capacity, as measured by the 6-minute walk distance, with increases of 42.2 meters at week 12 and 53.4 meters at week 24 (P < 0.0001).

The study also found that 64.6% of patients experienced risk improvement within 24 weeks, and the median time to clinical improvement (TTCI) was 131 days, indicating that TTCI is a valuable endpoint for assessing treatment efficacy in PAH, as it is not influenced by baseline risk status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time to clinical improvement: an appropriate surrogate endpoint for pulmonary arterial hypertension medication trials. Wang, A., Chen, M., Zhuang, Q., et al.[2023]

In the PATENT-1 study, riociguat significantly increased the proportion of patients with pulmonary arterial hypertension (PAH) achieving clinically relevant improvements in 6-minute walking distance (6MWD) and other key health indicators compared to placebo, with treatment-naïve patients showing a 21% increase in achieving 6MWD ≥380 m.

Riociguat also improved functional class and cardiac index in both treatment-naïve patients and those on background therapy, indicating its efficacy in enhancing overall patient outcomes in PAH management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of clinically relevant responder threshold criteria to evaluate the response to treatment in the phase III PATENT-1 study. Langleben, D., Galiè, N., He, J., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Ambrisentan for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH). [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Time to clinical improvement: an appropriate surrogate endpoint for pulmonary arterial hypertension medication trials. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Use of clinically relevant responder threshold criteria to evaluate the response to treatment in the phase III PATENT-1 study. [2017]