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Pabinafusp Alfa

This article discusses a clinical trial investigating the long-term use of Pabinafusp Alfa (JR-141) in male patients with Hunter Syndrome, also known as Mucopolysaccharidosis II (MPS II). The study aims to evaluate the drug’s safety and effectiveness in treating both central nervous system (CNS) and somatic symptoms of this rare genetic disorder over an extended period.

Table of Contents

What is PABINAFUSP ALFA?

PABINAFUSP ALFA, also known by its product code JR-141, is a new medication being studied for the treatment of Hunter syndrome, a rare genetic disorder[1]. It is classified as an orphan drug, which means it is specifically developed to treat a rare medical condition[1].

Medical Condition Treated

PABINAFUSP ALFA is designed to treat Mucopolysaccharidosis II, more commonly known as Hunter syndrome[1]. This is a rare genetic disorder that primarily affects males. It is caused by a lack of an enzyme that breaks down certain complex molecules in the body, leading to a buildup of these molecules in various organs and tissues.

How PABINAFUSP ALFA Works

While the exact mechanism is not fully described in the provided information, PABINAFUSP ALFA is likely an enzyme replacement therapy. It’s designed to replace or supplement the enzyme that is missing or deficient in people with Hunter syndrome. What makes this treatment unique is its potential ability to cross the blood-brain barrier, which could allow it to address both the body-wide (somatic) and brain (central nervous system or CNS) symptoms of the disease[1].

Clinical Trial Details

The clinical trial for PABINAFUSP ALFA is an extension study, which means it follows up on patients who participated in an earlier study. Here are some key details:

  • It’s a Phase 3 study, which is typically one of the final stages before a drug can be approved for general use.
  • The study is open-label, meaning both the researchers and participants know which treatment is being given.
  • There are two groups (cohorts) of participants:
    • Cohort A: Participants start receiving PABINAFUSP ALFA from Week 105 of the previous study.
    • Cohort B: Participants start receiving PABINAFUSP ALFA from Week 53 of the previous study.
  • The study will continue for up to 4 years for Cohort A and 5 years for Cohort B, or until the drug receives marketing approval in the participant’s country, whichever comes first[1].

Eligibility Criteria

To participate in this study, patients must meet certain criteria. Some key inclusion criteria are:

  • Male patients who completed the previous study (JR-141-GS31) without safety concerns.
  • Ability to provide informed consent (or have a legal representative provide consent).
  • Agreement to use effective contraception if applicable.

Some reasons why a patient might not be eligible (exclusion criteria) include:

  • Having received gene therapy treatment at any point.
  • Being unable to undergo a lumbar puncture (a procedure where a needle is inserted into the lower back to collect spinal fluid).
  • Having changed treatment from JR-141 to another drug (idursulfase) during the previous study.
  • Having a history of serious drug allergies or sensitivity to components of JR-141[1].

Study Objectives

The main goals of this study are:

  1. To evaluate the long-term effectiveness of PABINAFUSP ALFA on CNS symptoms in patients with Hunter syndrome.
  2. To assess the long-term effectiveness of PABINAFUSP ALFA on somatic (body-wide) symptoms.
  3. To evaluate the long-term safety of PABINAFUSP ALFA in patients with Hunter syndrome[1].

Endpoints

The study will measure several outcomes (endpoints) to determine how well PABINAFUSP ALFA is working and how safe it is. Some of these include:

  • Levels of certain substances (HS and DS) in the spinal fluid and blood.
  • Neuropsychological assessments (tests of brain function).
  • Quality of life assessments.
  • Liver and spleen size.
  • Shoulder range of motion.
  • Six-minute walk test (to assess physical endurance).
  • Pulmonary (lung) function tests.
  • Safety assessments, including monitoring for side effects and checking various laboratory tests[1].

Administration and Dosage

PABINAFUSP ALFA is given as an intravenous injection, which means it’s injected directly into a vein. The maximum daily dose is 2.0 mg/kg (milligrams per kilogram of body weight)[1].

Safety Considerations

As with any medical treatment, there are potential risks and safety considerations:

  • Patients will be monitored for adverse events (side effects) throughout the study.
  • Regular laboratory tests, physical examinations, and other assessments will be conducted to ensure patient safety.
  • Patients with a history of serious drug allergies or sensitivity to components of PABINAFUSP ALFA are not eligible for the study.
  • The study will also monitor for infusion-associated reactions, which can occur when receiving medications through an IV[1].

It’s important to note that this is an investigational treatment still being studied. While it shows promise, its full benefits and risks are still being evaluated. Patients and caregivers should discuss all potential treatment options with their healthcare providers.

Aspect Details
Study Type Phase 3 extension study, open-label, no control, 2 cohorts
Drug Pabinafusp Alfa (JR-141)
Condition Mucopolysaccharidosis II (Hunter Syndrome)
Primary Objectives Evaluate long-term efficacy on CNS symptoms and somatic symptoms, assess long-term safety
Key Measurements CSF HS and DS concentrations, neuropsychological assessments, quality of life, liver and spleen volume, shoulder range of motion, six-minute walk test
Duration Up to 4 years (Cohort A) or 5 years (Cohort B)
Dosage 2.0 mg/kg, administered intravenously
Key Eligibility Male patients who completed previous study (JR-141-GS31), no gene therapy treatment history

FAQ

  • What is the main purpose of this clinical trial? The main purpose of this clinical trial is to evaluate the long-term efficacy of Pabinafusp Alfa (JR-141) on central nervous system (CNS) symptoms in patients with Hunter Syndrome (MPS II).
  • Who is eligible to participate in this study? Eligible participants are male patients who completed the previous study (JR-141-GS31) and have no safety concerns. They must be able to provide informed consent or have a legally acceptable representative do so on their behalf.
  • How long will the study last? The study will continue for a maximum of 4 years for Cohort A and 5 years for Cohort B, or until Pabinafusp Alfa receives marketing approval in the participant's country and an access channel is established, whichever comes first.
  • What are some of the key measurements taken during the study? Key measurements include CSF (cerebrospinal fluid) concentrations of heparan sulfate (HS) and dermatan sulfate (DS), neuropsychological assessments, quality of life assessments, liver and spleen volume, shoulder range of motion, and various blood and urine tests.
  • Are there any specific exclusion criteria for the study? Yes, some exclusion criteria include having received gene therapy treatment, inability to undergo lumbar puncture, changing treatment from JR-141 to idursulfase during the previous study, and having a history of serious drug allergies or sensitivity to any component of JR-141.

Ongoing Clinical Trials on Pabinafusp Alfa

  • Long-term Safety and Efficacy Study of JR-141 (Pabinafusp Alfa) for Male Patients with Hunter Syndrome (Mucopolysaccharidosis II)

    Recruiting

    3 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Italy Poland Spain

  • Study on the Effects and Safety of JR-141 and Idursulfase for Patients with Hunter Syndrome

    Not recruiting

    3 1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Italy Poland Spain

Glossary

  • Mucopolysaccharidosis II (MPS II): Also known as Hunter Syndrome, this is a rare genetic disorder caused by a deficiency of the enzyme iduronate-2-sulfatase, leading to the accumulation of certain complex sugars in the body's cells.
  • Pabinafusp Alfa (JR-141): The investigational drug being studied in this clinical trial for the treatment of Hunter Syndrome. It is designed to cross the blood-brain barrier and address both CNS and somatic symptoms of the disease.
  • Central Nervous System (CNS): The part of the nervous system consisting of the brain and spinal cord, which is a primary focus of treatment in this study.
  • Somatic symptoms: Physical symptoms affecting the body, as opposed to mental or emotional symptoms. In Hunter Syndrome, these can include joint stiffness, breathing difficulties, and organ enlargement.
  • Cerebrospinal Fluid (CSF): A clear, colorless fluid that surrounds the brain and spinal cord, protecting them from injury. In this study, CSF is analyzed to measure levels of certain substances.
  • Heparan Sulfate (HS) and Dermatan Sulfate (DS): Complex sugar molecules that accumulate in the bodies of patients with Hunter Syndrome. Their levels in CSF, blood, and urine are measured as indicators of disease progression and treatment effectiveness.
  • Lumbar Puncture: A medical procedure to collect a sample of cerebrospinal fluid, typically performed by inserting a needle into the lower back. This is used in the study to obtain CSF samples for analysis.
  • Quality of Life (QoL) assessment: A measurement of a patient's overall well-being and ability to function in daily life, which is an important outcome in this study.
  • Six-minute walk test: A test that measures the distance an individual can walk in six minutes, used to assess physical endurance and mobility in this study.
  • Anti-JR-141 antibodies: Proteins produced by the immune system in response to JR-141. These are monitored as part of the safety assessment in the study.

References

  1. http://clinicaltrials.eu/trial/long-term-safety-and-efficacy-study-of-jr-141-pabinafusp-alfa-for-male-patients-with-hunter-syndrome-mucopolysaccharidosis-ii/