Evaluation of Safety, Tolerability, and Efficacy of Intravenous NVG-2089 in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Patients

Trial ID: 2024-515386-34-00
Protocol: NVG-2089-201
Sponsor: Nuvig Therapeutics Inc.

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Diseases & Conditions

Chronic inflammatory demyelinating polyradiculoneuropathy

Objectives

The primary objective of this study is to evaluate the **safety** and **tolerability** of NVG-2089 in participants with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). This is clinically relevant as it aims to ensure that NVG-2089 can be administered safely to patients, minimizing adverse effects while maintaining patient comfort and compliance.

Secondary objectives include:

To evaluate the efficacy of NVG-2089 in participants with CIDP.
To further evaluate the efficacy of NVG-2089 in participants with CIDP.
To characterize the pharmacokinetic (PK) profile of NVG-2089 in participants with CIDP.
To evaluate the immunogenicity of NVG-2089 and the impact of the presence of anti-drug antibodies (ADAs) on plasma PK concentrations and clinical safety.

These objectives are crucial for understanding the therapeutic potential and biological behavior of NVG-2089, as well as its interaction with the immune system, which can influence treatment outcomes and long-term safety.

Participants

The clinical trial involves a total of **30 participants** diagnosed with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The study population includes both male and female subjects, aged 18 years and older, who meet specific diagnostic criteria for CIDP or possible CIDP as per the EAN/PNS 2021 guidelines. Participants are either treatment-naïve or treatment-experienced, with the latter group having documented evidence of clinically meaningful deterioration or improvement with standard care therapy. The trial includes individuals who are capable of providing informed consent or have a legally authorized representative to do so. Participants are required to adhere to specific lifestyle considerations, such as discontinuing IVIg or SCIg therapy prior to dosing with the study drug. Female participants of childbearing potential must use double contraception and have negative pregnancy tests, while male participants must agree to use highly effective barrier contraception. The trial population was selected based on these criteria to ensure the safety and tolerability of NVG-2089 in individuals with CIDP.

Plans and Procedures

The clinical trial is designed to evaluate the **safety**, tolerability, and efficacy of the investigational product NVG-2089, administered as a **solution for infusion** in participants diagnosed with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. This is a Phase 2, open-label study, which means that both the researchers and participants are aware of the treatment being administered. The trial is expected to commence recruitment on April 30, 2025, and conclude by April 30, 2026, with a maximum treatment period of 14 days for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, diagnosis, and previous treatment history. The primary inclusion criteria require participants to be at least 18 years old and diagnosed with CIDP or possible CIDP according to the EAN/PNS 2021 criteria. Following the screening, eligible participants will receive the investigational product intravenously. The study will include follow-up visits to monitor the incidence, nature, and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), as well as clinically significant findings from laboratory tests, vital signs, electrocardiograms, and physical examinations.

The trial will also assess secondary endpoints, such as the percentage of treatment-naïve participants showing clinical improvement at Week 14, and the percentage of treatment-experienced participants meeting specific conditions of improvement or stability. Participants will be involved in the study for a duration that includes the treatment period and follow-up visits, with the total involvement not exceeding the trial's end date. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or non-compliance with the study protocol. The trial aims to provide valuable data on the pharmacokinetics and safety profile of NVG-2089, contributing to the understanding of its potential as a treatment for CIDP.

Treatment

The clinical trial involves the administration of **NVG-2089**, an investigational medication developed by NUVIG THERAPEUTICS INC. NVG-2089 is formulated as a **solution for infusion** and is intended for **intravenous use**. The active substance, NVG-2089, is classified as a protein of other origin. The trial is designed to evaluate the safety, tolerability, and efficacy of NVG-2089 in participants diagnosed with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The dosing regimen for NVG-2089 is specified in milligrams per kilogram (mg/kg), although the exact dosage and maximum daily dose are not explicitly defined in the provided data. The maximum treatment period for NVG-2089 administration is 14 days.

In this study, NVG-2089 is the sole investigational product, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are mentioned. The trial does not include a pediatric formulation of NVG-2089, and it is not classified as an orphan drug. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol. The trial's primary objective is to assess the safety and tolerability of NVG-2089 in the target population.

Efficacy

The efficacy of NVG-2089 in participants with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)** will be assessed through a series of predefined secondary endpoints. These endpoints include the percentage of treatment-naïve participants demonstrating evidence of clinical improvement (ECI) at Week 14. ECI is characterized by an improvement of 1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (adjusted INCAT) score, 4 points on the Inflammatory Rasch-built Overall Disability Scale (I-RODS), or an 8 kilopascal (kPa) increase in mean grip strength of the dominant hand.

For treatment-experienced participants, efficacy will be evaluated by the percentage of participants achieving ECI at Week 14, as well as those showing no worsening in adjusted INCAT scores between Weeks 4 and 14. Additionally, participants who experience worsening in adjusted INCAT scores between Day 1 and Week 4, without receiving rescue medication, followed by an improvement to baseline by Week 4 and maintained through Week 14, will also be considered. Changes from baseline over time in adjusted INCAT score, Medical Research Council (MRC) sum score, I-RODS disability scores, and mean grip strength will be measured to further assess efficacy.

Pharmacokinetic (PK) parameters of NVG-2089 concentrations in plasma will be analyzed, along with the incidence and characteristics of anti-drug antibodies (ADA) after dosing. The PK concentrations and safety profile in participants with ADA will also be evaluated. These assessments will be conducted at specified timepoints throughout the trial to ensure comprehensive evaluation of the drug's efficacy in the target population.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Males and females at least 18 years of age at the time of signing the ICF.
Diagnosed with CIDP or Possible CIDP according to criteria of the EAN/PNS 2021.
Must have an adjusted INCAT score as follows: a. Treatment-naïve participants: ≥2 at screening b. Treatment-experienced participants: 2-7 at screening Note: A score of 2 should be exclusively from leg disability component of adjusted INCAT. For participants with an adjusted INCAT score of ≥3 (and up to 7 for treatment-experienced; no upper limit for treatment-naïve) at study entry, there are no specific requirements for arm or leg scores.
Treatment-experienced participants: Participants who were treated with IVIg/SCIg at the time of screening must have documented evidence within 24 months of screening of: a. Clinically meaningful deterioration on treatment interruption or dose reduction of standard of care (SOC) therapy, determined by clinical examination documented in the medical records. Clinically meaningful deterioration is defined as one of the following: ≥1-point increase in adjusted INCAT score, decrease in I-RODS total score ≥4 points, decrease in MRC Sum score ≥3, grip strength worsening of ≥8 kPa (in either hand), or an equivalent deterioration based on information from medical records and at the Investigator’s judgement. OR b. Improvement in CIDP symptoms with SOC therapy based on information in medical records and at the Investigator’s judgement. In assessing the history of response to IVIg/SCIg, the Investigator should account for prior treatment (type, dose regimen, duration), pattern of response or non-response to treatment.
Treatments: a. Treatment-naïve participants: No prior treatment or off-treatment for CIDP (no treatment for at least 6 months prior to screening) with IVIg and/or SCIg and/or corticosteroids and/or efgartigimod and/or investigational therapies for CIDP Off-treatment participants must have demonstrated prior response to therapy as described in Inclusion Criterion 4a. OR b. Treatment-experienced participants: On stable dose of IVIg or SCIg with no disease exacerbations for 8 weeks prior to screening. Participants on IVIg must be on maintenance dose of 0.4 to 1 g/kg every 2 to 6 weeks (or equivalent) per EAN/PNS recommendation. Participants on SCIg should not exceed the dose of 0.4 g/kg per week. Participants must be willing to discontinue IVIg or SCIg at least 3 weeks (±1 week) prior to dosing with the study drug.
Female participants of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1.
Female participants who are sexually active with a male partner of reproductive potential must use double contraception (including a barrier contraceptive and another method) from at least 28 days prior to Screening and for 90 days after last dose of study drug; female participants must also refrain from oocyte donation for the purpose of reproduction during this period. Exceptions are made for surgically sterile participants, or post-menopausal females (defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels >40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy). Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
Male participants with female partners who are of reproductive potential must agree to the use of highly effective, barrier contraception for the duration of the study, and for 90 days after the last dose of study drug.
Participant is capable or has (a) legally authorized representative(s) (LAR[s]) capable of providin a signed informed consent which includes compliance with the requirements and restrictions listed in the ICF .

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Exclusion Criteria

Pure sensory or distal CIDP variants (EAN/PNS definition).
Participants who (intend to) use prohibited medications and therapies during the study.
Have received a live-attenuated vaccine within 28 days before screening. An inactivated, sub-unit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary.
History of being non-responder or loss of response to IVIg or SCIg per Investigator’s determination. In assessing the history of response or loss of response to IVIg/SCIg, the Investigator should account for prior treatment (type, dose regimen, duration), pattern of response or non-response to treatment. Note, participants who are on IVIg but relapsed on SCIg will be allowed to enter the study.
Previously participated in a study with NVG-2089 and have received at least one administration of study drug.
A known allergy to study drug and/or any of its components.
Current or past history (within 12 months of screening) of alcohol, drug, or medication abuse. Positive urine drug screen at screening visit suggesting drug abuse. Note: participants with positive urine drug screen due to physician-prescribed medications (such as benzodiazepine for anxiety) for a preexisting medical condition will be allowed to enroll. In these cases, the medical condition should be documented on the Medical History electronic case report form (eCRF), and the prescribed drug recorded in the Prior and Concomitant Medications eCRF.
Pregnant and lactating women and those intending to become pregnant during the study or are unwilling to apply an effective birth control method (such as implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence, or vasectomized partner) up to 90 days after last study drug administration.
Polyneuropathy of other causes, including the following: multifocal motor neuropathy; polyneuropathy associated with anti-myelin associated glycoprotein antibodies, polyneuropathy associated with monoclonal gammopathy; hereditary demyelinating neuropathy; polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin change syndromes; lumbosacral radiculoplexus neuropathy; polyneuropathy most likely due to diabetes mellitus; polyneuropathy most likely due to systemic illnesses; drug- or toxin-induced polyneuropathy.
Any other disease that could better explain the participant's signs and symptoms.
Any history of myelopathy or evidence of central demyelination.
Glycated hemoglobin (HbA1c) ≥7.5%
Any other known autoimmune disease that, in the opinion of the Investigator, would interfere with an accurate assessment of clinical symptoms of CIDP.
Severe psychiatric disorder (such as severe depression, psychosis, bipolar disorder) that in the opinion of the Investigator could create undue risk to the participant or could affect adherence with the study protocol.
Active liver disease, with history of ascites or hepatic encephalopathy, total bilirubin > 2 mg/dL (except in the case of documented Gilbert’s disease), or transaminases > 2 times upper limit of normal (ULN) at screening.
Hematology abnormalities at screening including: a. hemoglobin < 10 g/dL in males and <9 g/dL in females, or b. neutrophils < 1.5 × 10^9/L, or platelets <100 × 10^9/L"
Acute demyelinating neuropathies including Gullian-Barre syndrome
Chronic kidney disease as defined by estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m^2 at screening.
History of malignancy except adequately treated basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, or Incidental histological finding of Prostate cancer (TNM [tumor, nodes, and metastases classification] stage T1a or T1b). The above malignancies must be deemed cured by adequate treatment with no evidence of recurrence for at least 3 years prior to screening.
Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, or unstable or advanced ischemic heart disease, clinically significant cardiac dysrhythmia clinically significant ECG findings at screening (such as QTcF > 450 msec for males or > 470 msec for females), poorly controlled atrial fibrillation and/or other clinically significant cardiac abnormalities.
Clinically significant active or chronic uncontrolled bacterial, viral, or fungal infection at screening, including active viral infection at screening with: - Active Hepatitis B Virus (HBV): Hepatitis surface antigen (HBsAg) positive; - Active Hepatitis C Virus (HCV): serology positive for HCV-Ab; - Human Immunodeficiency Virus (HIV) positive serology."
Active suicidal ideation as measured by a most severe suicide ideation score of 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan) or 5 (Active Suicidal Ideation with Specific Plan and Intent) on the C-SSRS if the ideation occurred within 1 year of Screening, or participants who answered “Yes” on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior), if the attempt or acts were performed within 1 year of Screening, or participants who, in the opinion of the Investigator, present a serious risk of suicide
Clinical evidence of other significant serious disease, recent or planned major surgery, or any other reason which could confound the results of the study or put the participant at undue risk.
The following therapies are excluded: a. Within 1 month before screening: Prednisone or systemic corticosteroids Note: participants who are currently on IVIg/SCIg and have been previously treated with corticosteroids can be enrolled in treatment-experienced Cohorts 1 and 2 b. Within 3 months (or 5 half-lives of the drug, whichever is longer) before screening: plasma exchange or immunoadsorption, any Fc-containing therapeutic agents or other biological, or any other investigational or approved product. c. Within 6 months before screening: rituximab, alemtuzumab, any other monoclonal antibody, cyclophosphamide, interferon, tumor necrosis factor-alpha inhibitors, fingolimod, methotrexate, azathioprine, mycophenolate, any other immunomodulating or immunosuppressive medications.
Weight of ≥133 kg

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	30 Apr 2025	10
Bulgaria	Not Recruiting	30 Apr 2025	10
France	Not Recruiting	30 Apr 2025	20
Italy	Not Recruiting	30 Apr 2025	20
Poland	Not Recruiting	30 Apr 2025	19
Spain	Not Recruiting	30 Apr 2025	20