Clinical Study of Regulatory T Cells (Tregs) in the Treatment of Neurodegenerative Diseases

Phase 1

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis (ALS); Alzheimer's Disease(AD); Multiple System Atrophy, MSA
• Interventions: Biological: Autologous Human Polyclonal Regulatory T Cells Injection (NP001 Cell Injection)

• Registration Number: NCT06671236
• Lead Sponsor: Novabio Therapeutics

Brief Summary

An open, multi- center phase Ⅰ clinical study evaluating the safety and efficacy of autologous human polyclonal regulatory T cell injection (NP001 cell injection) in patients with Neurodegenerative diseases (ALS, MSA, AD).

Detailed Description

This is an open-label, non-randomized, multi-center clinical trial of single-agent NP001 cell injection in patients with with Neurodegenerative diseases (ALS, MSA, AD).

After subject consents to the study, an apheresis procedure will be performed to collect cells to manufacture the investigational product, NP001 cell injection. NP001 cell injection are manufactured ex vivo to yield enriched Tregs.

This study is evaluating NP001 cell injection at the dose of 1x E6 cells, 1x E7 cells, and 1x E8 cells/times, with up to 3 times separated by 4 weeks among dosing (intrathecally on Days 1, 29, and 57). Study subjects are then followed for several months to capture safety and efficacy parameters. The total duration of NP001 cell injection and follow-up interval on this protocol is approximately 12-months.

Study Timeline

• Study First Submitted: 2024-10-29
• Status Verified: 2024-11
• Study Start: 2024-11
• Study First Submitted QC: 2024-11-01
• Last Update Submitted: 2024-11-01
• Study First Posted: 2024-11-04
• Last Update Posted: 2024-11-04
• Primary Completion: 2026-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Patients must meet all of the following criteria to be eligible for enrollment in this study:

1. Male or female patients aged 18 to 70 years; 2. According to current international diagnostic criteria:

2. ALS: defined by the Gold Coast Diagnostic Criteria (Shefner, 2020) as having a diagnosis of sporadic or familial amyotrophic lateral sclerosis (ALS), diagnosed as a probable, probable, or definite patient with laboratory support according to the World Federation of Neurology El Escorial criteria;

3. MSA: UMSARS I (Question 11 omitted) score of 5 -17 and able to walk independently (i.e., able to walk for at least 40 meters without the use of crutches or walkers and without other support (e.g., holding the arm or touching)). Expected survival of at least 3 years in the opinion of the investigator. Normal cognition as assessed by the Montreal Cognitive Assessment (MOCA), i.e., ≥26.

4. AD: age 65 or above; Clinical diagnosis of AD (MoCA 10-20 and Clinical Dementia Rating Scale/CDR = 1) on stable doses of medication for at least three months, no clinically significant findings on blood tests, able to voluntarily provide written informed consent.

5. Must have an autologous T cell source sufficient to make NP001 T cells, defined as a peripheral CD3+ T cell count of > 800 cells/pl. or assay of available autologous Tregs with CD4, CD25, and FoxP3 expression greater than or equal to 50% by flow cytometry.

6. If there is a stable dose for more than one month prior to study entry. For example, patients with ALS can continue treatment with riluzole (Rilutek®) and/or edaravone (Radicava®); 5. Patients must have > two weeks after the end of major surgery and after the completion of participation in other research trials; 6. Patients must have recovered from clinical toxicity (CTCAE [5th Edition] toxicity values have resolved to < 2); 7. Serum creatinine less than or equal to 2.0 mg/dL; 8. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal; 9. Bilirubin < 1.5 (except Gilbert's disease); 10. Lung slow vital capacity (SVC) > 50% of predicted normal; 11. No history of abnormal bleeding tendency; 12. Informed consent must be obtained prior to performing any study-related procedures that are not part of standard medical care, with the understanding that the participant may withdraw from the study without influence for the future medical care.

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Exclusion Criteria

Subjects with any of the following cannot be enrolled in this study:

1. uncontrolled infection;
2. < 3 drugs do not adequately control hypertension;
3. Documented history of pulmonary embolism within 6 months of enrollment;
4. Clinically significant cardiology, defined as: myocardial infarction, NYHA-graded class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia, or ECG evidence of acute ischemia or abnormal conduction system within 6 months prior to enrollment;
5. Patients with a history of coronary artery bypass grafting or angioplasty will be evaluated by cardiology and considered on a case-by-case basis;
6. Seropositive for HIV, hepatitis B or hepatitis C;
7. Pregnant or lactating patients;
8. Patients of childbearing potential or males with partners of childbearing potential who are unwilling to use contraception;
9. Participation in any other interventional study;
10. Treatment with another investigational drug, biologic, or device within 30 days or 5 half-lives (whichever is longer) of the screening period. Patient participation in observational/non-interventional clinical studies will be discussed with the Medical Monitor;
11. Prior treatment with ALS, MSA or AD gene or cell therapy;
12. History of clinically significant tumor, liver or kidney disease, or other uncontrolled disease;
13. presence of a feeding tube;
14. Current use of antipsychotics, antiepileptic drugs (except benzodiazepines, gabapentin, pre-Bahrain) or class 1 (e.g., flecainide) or class 3 (e.g., amiodarone) antiarrhythmic drugs;
15. Subjects who, in the opinion of the investigator, are at significant risk of suicide;
16. Other conditions that the investigator considers unsuitable for enrollment.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Autologous Human Polyclonal Regulatory T Cells Injection (NP001 Cell Injection)	Autologous Human Polyclonal Regulatory T Cells Injection (NP001 Cell Injection)	Regulatory T cell therapy, intrathecal injection

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment Related adverse events (AEs)	6 months	Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs)
Identification of Maximum Tolerated Dose (MTD)	28 days	Incidence of dose-limiting toxicities (DLTs)

Secondary Outcome Measures

Name	Time	Method
Amyotrophic lateral sclerosis functional rating scale- revised (ALSFRS-R)	1 year	The ALSFRS-R is a simple, validated, and reliable tool for evaluating declines in function. It involves self-rating by patients on their ability and independence across 12 functional activities, with each question scored from 0 to 4 (4 means normal). The total score ranges from 0 (worst) to 48 (best), covering aspects of speech, swallowing, fine motor skills, gross motor skills, and respiratory function.
Unified Multiple System Atrophy Rating Scale (UMSARS)	1 year	UMSARS is composed of four subscales: UMSARS-I (12 items) rates patient-reported functional disability, UMSARS-II (14 items) assesses motor impairment based on a clinical examination, UMSARS-III records blood pressure and heart rate in the supine and standing positions, and UMSARS-IV (1 item) rates chore-based disability. Higher scores on the UMSARS indicate greater disability.
Montreal Cognitive Assessment (MoCA)	1 year	MoCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 30 points; a score of 26 or above is considered normal.
Clinical Dementia Rating (CDR)	1 year	CDR is a global rating device and estimated on the basis of a semistructured interview of the subject and the caregiver (informant) and on the clinical judgment of the clinician. CDR is calculated on the basis of testing six different cognitive and behavioral domains such as memory, orientation, judgment and problem solving, community affairs, home and hobbies performance, and personal care. The CDR is based on a scale of 0-3: no dementia (CDR = 0), questionable dementia (CDR = 0.5), MCI (CDR = 1), moderate cognitive impairment (CDR = 2), and severe cognitive impairment (CDR = 3).
Rasch Overall ALS Disability Scale (ROADS)	1 year	ROADS is a patient-reported outcome measure that assesses overall disability level in patients with ALS. The scale contains 28 items, each scored 0, 1, or 2.; The scale was constructed and validated using Rasch analyses - a modern test theory technique that produces linearly-weighted scales, meaning that a 1-point change is a quantifiable, consistent measurement of disability across the scale, and a 2-point change reflects twice the amount of disability.

Trial Locations

Locations (2)

Ascension Via Christi Clinic; 🇺🇸 Wichita, Kansas, United States

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China