Paraneoplastic Sensory NeuronopathyPhase 2NESPANCT06373211
Early Immunotherapy with Intravenous Immunoglobulin, Cyclophosphamide and Methylprednisolone in Patients with Anti-Hu-associated Paraneoplastic Sensory Neuronopathy
A Phase 2 study testing Immunoglobulins IV (CLAYRIG), Cyclophosphamide IV and Methylprednisolone IV in people with Paraneoplastic Sensory Neuronopathy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Paraneoplastic Neurological Syndromes are rare autoimmune complications linked to the presence of systemic cancer. Despite their autoimmune origin, they have historically shown little response to immunotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paraneoplastic Sensory Neuronopathy
- What is being tested?
- Immunoglobulins IV (CLAYRIG), Cyclophosphamide IV and Methylprednisolone IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteFrance
- Study dates
- 10 Jan 2025to Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old
- "Possible" sensory neuronopathy according to the criteria of Camdessanché et al. [2] with ONLS score ≥ 1
- Dominant picture of sensory ataxia (damage to the central nervous system and/or the neuromuscular junction is allowed, provided that it has a minor impact on the patient's disability)
- Positive anti-Hu antibodies in blood and/or cerebrospinal fluid
- Outpatient (modified Rankin Score (mRS) 2 or 3)
- Onset of neurological symptoms less than 3 months ago
- Free, informed, written and signed consent
- Affiliation to a social security or beneficiary scheme (except AME)
Who cannot join
- Known hypersensitivity to one of the treatments under study, to their metabolites, or to one of the excipients
- Absolute contraindications to IVIg: selective IgA deficiency, known thrombophilia, patients suffering from type I or II hyperprolinemia, hypersensitivity to human immunoglobulins
- Absolute contraindications to cyclophosphamide: vaccination against yellow fever in the 3 months preceding inclusion, acute urinary infection, pre-existing hemorrhagic cystitis, urinary tract obstruction, acute bone marrow failure
- Contraindication to methylprednisolone: live vaccines, or live attenuated vaccines within 3 months, infectious state or evolving virus (hepatitis, herpes, chickenpox, shingles)
- More than two courses of IVIg administered within 3 months before recruitment
- Other concomitant immunotherapy
Show all 14Show fewer
- Other cause of immunosuppression (acquired or congenital)
- Treatment with checkpoint inhibitors in progress or completed less than 3 months previously
- Woman or man without effective contraception
- Pregnant or breastfeeding woman
- History of psychiatric or general illnesses that may contraindicate treatment
- Patients unable to complete the follow-up required by the study
- Patients under guardianship or curatorship
- Patient deprived of liberty by a judicial or administrative decision
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Pitié-Salpêtrière
Paris, 75013
Dimitri Psimaras, MD, dimitri.psimaras@aphp.fr
Alice LEPRINCE-LAURENGE, MD, alice.laurenge@aphp.fr
About this study
Paraneoplastic Neurological Syndromes are rare autoimmune complications linked to the presence of systemic cancer. Despite their autoimmune origin, they have historically shown little response to immunotherapy. The reason for this failure is probably related to too late administration of immunotherapy, at a stage where the inflammation has already disappeared and irreversible neuronal loss has occurred. The protocol focuses on patients with anti-Hu antibody sensory neuronopathy. This single arm trial consists of an early immunotherapy combining Intravenous Immunoglobulin (IVIG) for 3 months, cyclophosphamide and methylprednisolone for 6 months, at the rate of 1 cycle per month. The percentage of patients with clinical improvement will be evaluated (ONLS) at 3 months. The tolerance of the treatment will also be evaluated as well as other functional scales at 3 and 6 months.
- Conditions
- Paraneoplastic Sensory Neuronopathy
- Being tested
- Immunoglobulins IV (CLAYRIG), Cyclophosphamide IV, Methylprednisolone IV
- Keywords
- Sensory neuronopathy, Paraneoplastic syndrome, Early immunotherapy
- Medical subject headings
- Paraneoplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunoglobulins IV (CLAYRIG)Drug
Patients will be treated with cycles of :
- Intravenous (IV) immunoglobulins: 2 g/kg per cycle, over 3 to 5 days (D1 to D3 or D5).
Cycles will be administered every 4 weeks for a total of 3 first cycles
Cyclophosphamide IVDrug
Patients will be treated with cycles of :
- Cyclophosphamide IV: 1 g on the first day (D1). Cycles will be administered every 4 weeks for a total of 6 cycles
Methylprednisolone IVDrug
Patients will be treated with cycles of :
Methylprednisolone IV: 1 g/day for 3 days (D1 to D3). Cycles will be administered every 4 weeks for a total of 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| Early immunotherapy | Experimental | Early immunotherapy with intravenous immunoglobulin, cyclophosphamide and methylprednisolone Receives: Drug: Immunoglobulins IV (CLAYRIG); Drug: Cyclophosphamide IV; Drug: Methylprednisolone IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 months
Measured: At 3 months
Secondary outcomes (7)
Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 and 6 months
Measured: At 3 months and at 6 months
Percentage of patients with improvement in the ataxic component on the Score of Ataxia scale at 3 and 6 months
Measured: At 3 months and at 6 months
Percentage of patients with improvement in neuropathic pain on the Numeric Rating Scale (NRS) at 3 and 6 months
Measured: At 3 months and at 6 months
Percentage of patients with functional improvement on the modified Rankin Score (mRS) at 3 and 6 months
Measured: At 3 months and at 6 months
Percentage of patients with functional improvement on the Barthel Index (BI) at 3 and 6 months
Measured: At 3 months and at 6 months
Percentage of patients alive and without tumor progression at 6 months
Measured: At 6 months
Tolerance to treatment
Will be assessed by the frequency and severity of expected and unexpected adverse effects recorded during treatment
Measured: Through study completion, a maximum of 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2024
- Study start10 Jan 2025
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paraneoplastic Sensory NeuronopathyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dimitri Psimaras, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06373211
- Sponsor's protocol ID
- APHP230701
- Other IDs
- 2023-506942-22-01, 2023
- Acronym
- NESPA
- Status last verified
- Feb 2025
- First submitted
- 15 Apr 2024
- Last updated
- 17 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Immunotherapy with Intravenous Immunoglobulin, Cyclophosphamide and Methylprednisolone in Patients with Anti-Hu-associated Paraneoplastic Sensory Neuronopathy
- ClinicalTrials.gov ID
- NCT06373211
- Acronym / sponsor ID
- NESPA / APHP230701
- Conditions
- Paraneoplastic Sensory Neuronopathy
- Keywords
- Sensory neuronopathy, Paraneoplastic syndrome, Early immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 10 Jan 2025 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 18 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Paraneoplastic Neurological Syndromes are rare autoimmune complications linked to the presence of systemic cancer. Despite their autoimmune origin, they have historically shown little response to immunotherapy. The reason for this failure is probably related to too late administration of immunotherapy, at a stage where the inflammation has already disappeared and irreversible neuronal loss has occurred. The protocol focuses on patients with anti-Hu antibody sensory neuronopathy. This single arm trial consists of an early immunotherapy combining Intravenous Immunoglobulin (IVIG) for 3 months, cyclophosphamide and methylprednisolone for 6 months, at the rate of 1 cycle per month. The percentage of patients with clinical improvement will be evaluated (ONLS) at 3 months. The tolerance of the treatment will also be evaluated as well as other functional scales at 3 and 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Early immunotherapy | Experimental | Drug: Immunoglobulins IV (CLAYRIG), Drug: Cyclophosphamide IV, Drug: Methylprednisolone IVEarly immunotherapy with intravenous immunoglobulin, cyclophosphamide and methylprednisolone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years old
- "Possible" sensory neuronopathy according to the criteria of Camdessanché et al. [2] with ONLS score ≥ 1
- Dominant picture of sensory ataxia (damage to the central nervous system and/or the neuromuscular junction is allowed, provided that it has a minor impact on the patient's disability)
- Positive anti-Hu antibodies in blood and/or cerebrospinal fluid
- Outpatient (modified Rankin Score (mRS) 2 or 3)
Key exclusion criteria (14 listed)
- Known hypersensitivity to one of the treatments under study, to their metabolites, or to one of the excipients
- Absolute contraindications to IVIg: selective IgA deficiency, known thrombophilia, patients suffering from type I or II hyperprolinemia, hypersensitivity to human immunoglobulins
- Absolute contraindications to cyclophosphamide: vaccination against yellow fever in the 3 months preceding inclusion, acute urinary infection, pre-existing hemorrhagic cystitis, urinary tract obstruction, acute bone marrow failure
- Contraindication to methylprednisolone: live vaccines, or live attenuated vaccines within 3 months, infectious state or evolving virus (hepatitis, herpes, chickenpox, shingles)
- More than two courses of IVIg administered within 3 months before recruitment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immunoglobulins IV (CLAYRIG)Patients will be treated with cycles of : - Intravenous (IV) immunoglobulins: 2 g/kg per cycle, over 3 to 5 days (D1 to D3 or D5). Cycles will be administered every 4 weeks for a total of 3 first cycles | Drug | Early immunotherapy |
| Cyclophosphamide IVPatients will be treated with cycles of : - Cyclophosphamide IV: 1 g on the first day (D1). Cycles will be administered every 4 weeks for a total of 6 cycles | Drug | Early immunotherapy |
| Methylprednisolone IVPatients will be treated with cycles of : Methylprednisolone IV: 1 g/day for 3 days (D1 to D3). Cycles will be administered every 4 weeks for a total of 6 cycles | Drug | Early immunotherapy |
Primary outcome
Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 months
Time frame: At 3 months
7 secondary outcomes
Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 and 6 months
Time frame: At 3 months and at 6 months
Percentage of patients with improvement in the ataxic component on the Score of Ataxia scale at 3 and 6 months
Time frame: At 3 months and at 6 months
Percentage of patients with improvement in neuropathic pain on the Numeric Rating Scale (NRS) at 3 and 6 months
Time frame: At 3 months and at 6 months
Percentage of patients with functional improvement on the modified Rankin Score (mRS) at 3 and 6 months
Time frame: At 3 months and at 6 months
Percentage of patients with functional improvement on the Barthel Index (BI) at 3 and 6 months
Time frame: At 3 months and at 6 months
Percentage of patients alive and without tumor progression at 6 months
Time frame: At 6 months
Tolerance to treatment
Time frame: Through study completion, a maximum of 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2025.
- Individual participant dataSharing planned: Yes. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dimitri Psimaras, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Immunoglobulins IV (CLAYRIG), Cyclophosphamide IV and Methylprednisolone IV in people with Paraneoplastic Sensory Neuronopathy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dimitri Psimaras, MD (+33 1 42 16 04 35, dimitri.psimaras@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 months (time frame: At 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2025.