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Posenacaftor

Posenacaftor is an investigational drug being studied for the treatment of cystic fibrosis (CF). This article explores recent clinical trials that are evaluating the efficacy and safety of Posenacaftor in combination with other drugs for adults with CF, particularly those with rare genetic mutations. These trials aim to provide new treatment options for patients who may not respond to currently available therapies.

Table of Contents

What is POSENACAFTOR?

POSENACAFTOR, also known as PTI-801, is a promising new medication being studied for the treatment of cystic fibrosis (CF)[1]. Cystic fibrosis is a genetic disorder that affects the lungs, digestive system, and other organs, causing thick, sticky mucus to build up and leading to various health problems.

This drug is part of a combination therapy that includes two other medications: dirocaftor and nesolicaftor. Together, these three drugs are being tested to see how well they can help people with CF, especially those with rare genetic mutations that cause the disease[2].

How POSENACAFTOR Works

POSENACAFTOR belongs to a class of drugs called CFTR modulators. CFTR stands for Cystic Fibrosis Transmembrane Conductance Regulator, which is the protein that is faulty in people with CF. This medication works by helping the CFTR protein function better, which can improve the symptoms of cystic fibrosis[1].

Clinical Trials

POSENACAFTOR is currently being studied in clinical trials to evaluate its effectiveness and safety. Two important studies are underway:

  1. A Phase III trial called CHOICES, which is testing the combination of dirocaftor, posenacaftor, and nesolicaftor in adults with CF who are 18 years or older[1].
  2. A Phase IIb trial, also called CHOICES, which is similar to the Phase III trial but focuses on specific groups of CF patients[2].

Both trials are designed to be multicentre, randomized, double-blind, and placebo-controlled. This means that the studies are being conducted at multiple hospitals or clinics, participants are randomly assigned to either receive the medication or a placebo (a substance with no active ingredients), and neither the patients nor the researchers know who is receiving which treatment until the study is complete.

Eligibility Criteria

To participate in these clinical trials, patients must meet certain criteria. Some key requirements include:

  • Being 18 years of age or older
  • Having a confirmed diagnosis of cystic fibrosis
  • Having stable CF disease
  • Having a lung function (FEV1) between 40% and 90% of predicted normal values
  • Not currently taking other CFTR modulators
  • Not having certain common CF mutations (like F508del)

It’s important to note that these are just some of the criteria, and there are additional requirements and exclusions[1][2].

Potential Benefits

The clinical trials are measuring several outcomes to determine how well POSENACAFTOR and its companion drugs work. Some potential benefits being studied include:

  • Improved lung function, measured by FEV1 (Forced Expiratory Volume in 1 second, which is the amount of air a person can forcefully exhale in one second)
  • Reduced sweat chloride levels (a key indicator of CF severity)
  • Increased body weight
  • Improved quality of life, as measured by a special questionnaire for CF patients

These outcomes are being measured after 4, 6, and 8 weeks of treatment to see how quickly and effectively the medication works[1][2].

Safety and Side Effects

As with any new medication, researchers are carefully monitoring the safety of POSENACAFTOR. The clinical trials are tracking any side effects or adverse events that occur during treatment. This includes monitoring through:

  • Regular blood tests
  • Physical examinations
  • Electrocardiograms (ECGs) to check heart function
  • Vital sign measurements

It’s important to remember that the full safety profile of POSENACAFTOR is still being established through these clinical trials[2].

Administration

POSENACAFTOR is being tested as an oral medication in the form of a hard capsule. In the clinical trials, the maximum daily dose being tested is 600 mg. The treatment period in the studies lasts up to 16 weeks[1][2].

It’s important to note that POSENACAFTOR is still an investigational drug and is not yet approved for general use. If you have cystic fibrosis and are interested in this treatment, you should discuss it with your healthcare provider to see if participating in a clinical trial might be appropriate for you.

Aspect Details
Drug Combination Posenacaftor (PTI-801) + Dirocaftor + Nesolicaftor
Study Design Phase IIb/III, multicentre, randomized, double-blind, placebo-controlled, crossover
Target Population Adults (≥18 years) with CF and rare CFTR mutations
Primary Endpoint Mean ppFEV1 after 4, 6, and 8 weeks of treatment
Secondary Endpoints Sweat chloride levels, body weight, quality of life (CFQ-R), safety assessments
Treatment Duration 8 weeks for primary endpoint, up to 24 weeks for secondary endpoints
Dosage Maximum daily dose of 600 mg Posenacaftor
Administration Route Oral (capsule)

FAQ

  • What is Posenacaftor and how does it work? Posenacaftor is an investigational drug that belongs to a class of medications called CFTR modulators. It works by helping the defective CFTR protein function more effectively in people with cystic fibrosis, potentially improving lung function and other CF-related symptoms.
  • Who is eligible to participate in these clinical trials? The trials are primarily for adults (18 years or older) with cystic fibrosis who have rare CFTR mutations. Participants must meet specific criteria, including having clinically stable CF disease, a forced expiratory volume (FEV1) between 40% and 90% of predicted, and a body mass index (BMI) between 16 and 30 kg/m2.
  • What is the main goal of these clinical trials? The main objective of these trials is to evaluate the efficacy and safety of Posenacaftor in combination with other drugs (Dirocaftor and Nesolicaftor) compared to placebo in CF patients with rare CFTR mutations, both with and without pre-selection based on organoid response.
  • How long do the treatment periods last in these trials? The primary endpoint in these trials is measured after 8 weeks of treatment. However, the studies also evaluate the effects of the drug combination over longer periods, up to 24 weeks in some cases.
  • What are the main outcomes being measured in these trials? The primary outcome is the change in lung function, measured by the percent predicted forced expiratory volume in 1 second (ppFEV1). Secondary outcomes include changes in sweat chloride levels, body weight, quality of life (measured by the CFQ-R respiratory domain), and various safety and tolerability assessments.

Ongoing Clinical Trials on Posenacaftor

  • Study on the Effects of Dirocaftor, Posenacaftor, and Nesolicaftor for Adults with Cystic Fibrosis

    Not yet recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Czechia Denmark Germany Italy The Netherlands +3

  • Study on the Effects of Dirocaftor, Posenacaftor, and Nesolicaftor for Adults with Cystic Fibrosis

    Not recruiting

    1
    Investigated diseases:
    Investigated drugs:
    Belgium Czechia France Germany Italy The Netherlands +3

Glossary

  • Cystic Fibrosis (CF): A genetic disorder that affects the lungs, pancreas, and other organs, causing thick, sticky mucus to build up and leading to infections and breathing problems.
  • CFTR: Cystic Fibrosis Transmembrane Conductance Regulator, the protein that is defective in people with CF.
  • FEV1: Forced Expiratory Volume in 1 second, a measure of lung function that indicates how much air a person can exhale in one second.
  • ppFEV1: Percent predicted Forced Expiratory Volume in 1 second, which compares a person's FEV1 to what would be expected for someone of similar age, height, and sex without CF.
  • Sweat chloride test: A diagnostic test for CF that measures the amount of salt in a person's sweat. People with CF typically have higher levels of chloride in their sweat.
  • CFTR modulator: A type of medication that helps the defective CFTR protein work more effectively in people with CF.
  • Organoid: A tiny, simplified version of an organ grown in a laboratory, used in these studies to predict a patient's response to treatment.
  • CFQ-R: Cystic Fibrosis Questionnaire-Revised, a tool used to measure quality of life in people with CF.
  • Placebo: An inactive substance used in clinical trials to compare the effects of a drug against no treatment.
  • Double-blind: A study design where neither the participants nor the researchers know who is receiving the actual treatment and who is receiving the placebo.

References

  1. http://clinicaltrials.eu/trial/study-on-the-effects-of-dirocaftor-posenacaftor-and-nesolicaftor-for-adults-with-cystic-fibrosis/
  2. http://clinicaltrials.eu/trial/study-on-the-effects-of-dirocaftor-posenacaftor-and-nesolicaftor-for-adults-with-cystic-fibrosis-2/