NT-I7 for Progressive Multifocal Leukoencephalopathy
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
Must not be taking: Immune-suppressive medications
Disqualifiers: Autoimmune CNS, Immune-mediated vital organ, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?Background:
Progressive multifocal leukoencephalopathy (PML) is a brain infection. It is caused by a virus. PML can happen in people with a weakened immune system. PML is associated with cognitive and visual impairment as well as motor and speech disturbances. There is no treatment for PML. Researchers want to see if a new drug can help.
Objective:
To see if the drug NT-I7 can help increase lymphocyte numbers, which may help control PML infection.
Eligibility:
Adults ages 18 and older with PML who are enrolled in Protocol #13-N-0017.
Design:
Participants will be screened under Protocol #13-N-0017.
Participants will have a 7-day inpatient stay, outpatient visits, and follow-up phone calls.
Participants will have a medical history and physical exam. They will give urine samples. Blood will be drawn from an arm vein or through an intravenous (IV) catheter.
Participants will get up to 3 doses of NT-I7. It will be given by injection into the muscle.
Participants will have lumbar punctures ( spinal taps ). A thin needle will be inserted into the spinal canal in the lower back. Cerebrospinal fluid will be removed. X-ray may be used to guide the procedure.
Participants will have magnetic resonance imaging (MRI) of the brain. The MRI scanner is a metal cylinder surrounded by a magnetic field. During MRIs, participants will lie on a table that slides in and out of the scanner. Soft padding or a coil will be placed around their head. They will get gadolinium, a contrast agent, through an IV catheter.
Participation will last for 12 to 19 months.
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Will I have to stop taking my current medications?
The trial requires that you stop ongoing treatment with immune-suppressive medications, except for short-term use of topical steroids or systemic steroids for less than two weeks.
What data supports the effectiveness of the drug NT-I7 for treating progressive multifocal leukoencephalopathy?
Research shows that recombinant human interleukin-7 (a component of NT-I7) has been used successfully in patients with progressive multifocal leukoencephalopathy, leading to improved immune responses and clinical outcomes. In one case, it helped clear the virus causing the disease and improved the patient's condition.
12345Is NT-I7 (Efineptakin alfa) safe for humans?
Research in nonhuman primates showed that a treatment similar to NT-I7, called MVA-hIL-7-Fc, was safe and did not cause any acute adverse reactions. This suggests that NT-I7 may be generally safe in humans, but more specific human data would be needed for confirmation.
13467How is the drug NT-I7 different from other treatments for progressive multifocal leukoencephalopathy?
NT-I7 is unique because it uses interleukin-7, a protein that boosts the immune system by increasing T cells, which are crucial for fighting infections like the JC virus that causes progressive multifocal leukoencephalopathy. There are no standard treatments for this condition, making NT-I7 a novel option.
12457Eligibility Criteria
Adults over 18 with Progressive Multifocal Leukoencephalopathy (PML) and low lymphocyte counts, enrolled in Protocol #13-N-0017. Participants must be able to travel for study visits, provide consent, follow procedures, and use reliable birth control if applicable. Excludes those on immune-suppressive meds (except short-term steroids), with autoimmune CNS diseases or conditions that could affect the trial.Inclusion Criteria
My CD4 or CD8 cell count is 200 or less and can't be quickly fixed.
I am 18 years old or older.
You have been diagnosed with a specific brain infection called PML using specific criteria from 2013.
+5 more
Exclusion Criteria
Unwilling to have coded samples and/or data saved or used in other studies
You are currently receiving experimental treatments for PML that could affect the study results.
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with study participation; or not in the best interest of the subject to participate, in the opinion of the treating investigator
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Initial Treatment
Participants receive up to 3 doses of NT-I7 by injection into the muscle, with inpatient observation for the first 7 days following any experimental drug dosing.
7 days
7-day inpatient stay
Second Inpatient Stay
Participants return for a second 7-day inpatient stay by Day 21.
7 days
7-day inpatient stay
Outpatient Visits
Scheduled outpatient visits at NIH at month 2, 3, 6, 9, and 12 following any drug dosing.
12 months
5 outpatient visits
Follow-up
Follow-up phone calls will be conducted at month 4, 5, 7, and 8 to monitor safety and effectiveness.
4 months
4 follow-up phone calls
Participant Groups
The trial is testing NT-I7, a new drug designed to boost lymphocyte numbers which may help fight PML infection. It involves an initial 7-day hospital stay followed by outpatient visits and phone calls for up to 19 months. Procedures include injections of NT-I7 into the muscle, lumbar punctures, blood draws, urine samples, and MRI scans with contrast agents.
1Treatment groups
Experimental Treatment
Group I: NT-I7Experimental Treatment1 Intervention
480 microgram/kg IM (initial dose)
NT-I7 is already approved in United States for the following indications:
🇺🇸 Approved in United States as NT-I7 for:
- Orphan drug designation for glioblastoma multiforme
- Orphan drug designation for advanced pancreatic cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Institute of Neurological Disorders and Stroke (NINDS)Lead Sponsor
NeoImmuneTechIndustry Sponsor
References
Treatment of progressive multifocal leukoencephalopathy with interleukin 7. [2015]No reliable treatment options are known for progressive multifocal leukoencephalopathy with underlying immunodeficiency. We describe successful compassionate use of recombinant human interleukin 7 in a patient with idiopathic CD4+ T-cell lymphocytopenia.
Efficacy of recombinant human interleukin 7 in a patient with severe lymphopenia-related progressive multifocal leukoencephalopathy. [2020]In this study, we report the case of a patient with profound lymphopenia after allogenic bone marrow transplantation who developed severe progressive multifocal leukoencephalopathy. Single-agent recombinant human interleukin-7 therapy was associated with restoration of anti-John Cunningham polyomavirus (JCV) T-cell responses, JCV clearance from cerebrospinal fluid, and a dramatic clinical improvement.
Intravenous injection of a novel viral immunotherapy encoding human interleukin-7 in nonhuman primates is safe and increases absolute lymphocyte count. [2023]Persistence of an immunosuppression, affecting both the innate and adaptive arms of the immune system, plays a role in sepsis patients' morbidity and late mortality pointing to the need for broad and effective immune interventions. MVA-hIL-7-Fc is a non-replicative recombinant Modified Vaccinia virus Ankara encoding the human interleukin-7 fused to human IgG2 Fc fragment. We have shown in murine sepsis models the capacity of this new virotherapy to stimulate both arms of the immune system and increase survival. Herein, an exploratory study in nonhuman primates was performed following a single intravenous injection of the MVA-hIL-7-Fc used at the clinical dose to assess its safety and biological activities. Four cynomolgus macaques were followed for 3 weeks post-injection (p.i), without observed acute adverse reactions. Circulating hIL-7-Fc was detected during the first 3-5 days p.i with a detection peaking at 12 h p.i. IL-7 receptor engagement and downstream signal transduction were detected in T cells demonstrating functionality of the expressed IL-7. Expansion of blood lymphocytes, mainly CD4 and CD8 naïve and central memory T cells, was observed on day 7 p.i. together with a transient increase of Ki67 expression on T lymphocytes. In addition, we observed an increase in circulating B and NK cells as well as monocytes were albeit with different kinetics and levels. This study indicates that a vectorized IL-7-Fc, injected by intravenous route at a relevant clinical dose in a large animal model, is active without adverse reactions supporting the clinical development of this novel virotherapy for treatment of sepsis patients.
Interleukin-7 treatment of PML in a patient with idiopathic lymphocytopenia. [2018]To describe the compassionate use of interleukin-7 (IL-7) for treatment of progressive multifocal leukoencephalopathy (PML) in the setting of idiopathic CD8+ greater than CD4+ lymphocytopenia.
Outcome of Progressive Multifocal Leukoencephalopathy Treated by Interleukin-7. [2022]Restoring anti-JC virus (JCV) immunity is the only treatment of progressive multifocal leukoencephalopathy (PML). Interleukin-7 is a cytokine that increases number and function of T cells. We analyzed a population of PML patients who received recombinant human IL-7 (rhIL-7) to estimate survival and its determinants.
Biochemical characterization of a new recombinant TNF receptor-hyFc fusion protein expressed in CHO cells. [2015]The currently used Tumor Nectosis Factor (TNF)-α blockers such as infliximab, adalimumab and etanercept have Fc regions of the human IgG1 subtype have advantages in terms of in vivo half-life, however these could raise potential concerns for unwanted effector-mediated effects, such as antibody dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). To address this issue, we constructed a novel hybrid protein with decreased ADCC and CDC potentials by fusing the TNF receptor to a hybrid Fc (hyFc) containing CH2 and CH3 regions of IgG4 and highly flexible hinge regions of IgD which neither has ADCC and CDC activities. The resulting fusion protein, TNFR-hyFc, was over-expressed in CHO cells. For use as a pre-clinical material in pharmacology, PK and toxicological evaluations were carried out for biochemical characterization which was then compared with etanercept that has similarity in structure. Amino acid composition analysis and peptide mapping showed that the expressed TNFR-hyFc matched the theoretical composition derived from the DNA sequence. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) showed that TNFR-hyFc is 2.9 kDa larger than etanercept. MALDI-TOF after removal of N-glycans by PNGase treatment showed that TNFR-hyFc is 3.9 kDa larger than etanercept. Isoelectric focusing and monosaccharide analysis showed that TNFR-hyFc is slightly more acidic than etanercept. N-terminal amino acid sequencing showed that N-terminal heterogeneity is present in both TNFR-hyFc and etanercept, although the ratios are somewhat different. Glycan analysis showed that the main glycan form is bi-antennary, similar to etanercept.
Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. [2022]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Emerging oncotherapeutic strategies require the induction of an immunostimulatory tumor microenvironment (TME) containing numerous tumor-reactive CD8+ T cells. Interleukin-7 (IL-7), a T-cell homeostatic cytokine, induces an antitumor response; however, the detailed mechanisms underlying the contributions of the IL-7 to TME remain unclear. Here, we aimed to investigate the mechanism underlying the induction of antitumor response by hybrid Fc-fused long-acting recombinant human IL-7 (rhIL-7-hyFc) through regulation of both adaptive and innate immune cells in the TME.