Amyotrophic Lateral SclerosisPhase 2/3NATURALNCT06391645
Nerve Growth Factor Encapsulated With 2-methacryloyloxyethyl Phosphorylcholine Nanocapsules in the Treatment of Amyotrophic Lateral Sclerosis
A Phase 2/3 study testing Nerve Growth Factor in people with Amyotrophic Lateral Sclerosis, run by Beijing Tiantan Hospital.
Trial summary
Amyotrophic lateral sclerosis (ALS) is one of the most lethal neurodegenerative diseases, with most patients dying from respiratory failure 3-5 years after the onset. The purpose of this study is to explore the efficacy and safety of nerve growth factor (NGF) encapsulated with 2-methacryloyloxyethyl phosphorylcholine… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Nerve Growth Factor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- May 2024to Dec 2026
- Phase
- Phase 2/3
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-80 years old;
- Confirmed or possible familial or sporadic ALS diagnosed according to the revised El Escorial criteria;
- 6 months ≤disease duration ≤ 3 years, (onset time is defined as the time of the first occurrence of myasthenia);
- Forced vital capacity (FVC) ≥ 85% of predicted value (based on gender, height and age);
- Informed consent signed.
Who cannot join
- Patients undergoing endotracheal intubation, non-invasive or mechanical ventilation;
- Patients with diaphragmatic pacemakers;
- Allergy to any component of the investigational medication, or any other allergic history that researchers deem necessary to be vigilant about;
- Local skin infection or other suspicious signs of infection at the injection site;
- Known hemorrhagic tendency (including but not limited to: platelet count \<100×109/ L; on therapy of heparin, activated partial thromboplastin time (APTT) ≥35s; on therapy of warfarin, international normalized ratio (INR) >1.7; on therapy of novel oral anticoagulants; with direct thrombin or factor Xa inhibitor; accompanied with coagulopathy such as hemophilia);
- Severe cardiac insufficiency before randomization (comply with New York College of Cardiology (NYHA) Cardiac Function Class III, IV);
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- Suffering from infectious diseases: hepatitis, tuberculosis, acquired immunodeficiency syndrome, etc;
- Psychiatric disorders diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria; or with suicidal intentions;
- Women/men with desire to conceive during the experiment, and patients with pregnancy and lactation;
- Difficulty in verbal communication, inability to communicate, understand or follow instructions, inability to cooperate with treatment and evaluation;
- Combining with history of alcohol and drug abuse;
- Unable to cooperate in follow-up due to geographical or other reasons;
- Patients participated in other clinical trials or used other biologics, drugs, or devices under study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Amyotrophic lateral sclerosis (ALS) is one of the most lethal neurodegenerative diseases, with most patients dying from respiratory failure 3-5 years after the onset. The purpose of this study is to explore the efficacy and safety of nerve growth factor (NGF) encapsulated with 2-methacryloyloxyethyl phosphorylcholine (MPC) nanocapsules in the treatment of ALS patients.
Read the detailed description
Amyotrophic lateral sclerosis (ALS) is one of the most lethal neurodegenerative diseases. Most patients die due to respiratory failure 3-5 years after disease onset. Due to the low permeability and blocking of the blood-brain barrier (BBB) on more than 95% of all kinds of drugs, the drug treatment of ALS is relatively limited. Although a series of studies have been carried out on new therapies to ALS, such as monoclonal antibodies represented by ozanezumab and antisense oligonucleotides represented by tofersen, the conclusions are mostly limited to safety evaluation.
Nerve growth factor (NGF) provides protection and/or regeneration for neurons in the peripheral and central nervous system (CNS), which is considered to be a nerve regeneration agent with great therapeutic potential. The phase I clinical trial of intravenous recombinant human nerve growth factor (rhNGF) showed that, on the premise of ensuring safety, only a trace of NGF (3.6-7.38 ng/ml within 5 minutes) was detected in the plasma samples of the subjects who were injected with rhNGF 1.0 μg/kg (the maximum dose of this trial design).
In purpose of improving the therapeutic effect of NGF, the investigators plan to encapsulate NGF in nanoparticles linked by 2-methacryloyloxyethyl phosphorylcholine (MPC), consisting of one molecule of choline and one molecule of acetylcholine analog. After intravenous administration, the drug particles are effectively delivered to the CNS via receptor-mediated transcytosis (RMT) with the help of acetylcholine transporter and choline transporter widely expressed on brain capillary endothelial cells. The animal experiments have confirmed that intravenous injection of MPC encapsulated NGF capsule [n(NGF)] can effectively prolong the survival time of SOD1G93A mice, reduce the body weight loss and delay the time of dyskinesia onset compared with NGF. Similar results were obtained in the rhesus monkey model.
The purpose of this study is to explore the efficacy and safety of NGF encapsulated with MPC nanocapsules in the treatment of ALS patients.
This is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. The trial planned to enroll 60 ALS patients, aged 18-80 years, with disease duration 6 months to 3 years, with forced vital capacity (FVC) ≥ 85% of predicted value.
Patients will be randomly assigned to one of the following 3 groups at 1:1 ratio.
Treatment group 1: NGF 60ml wrapped in MPC nanomaterials (dose was given as 320 μg/ml) was injected intravenously every week for 12 weeks, including one administration at the starting point for a total of 13 times, as well as maintaining original basic drugs and rehabilitation treatment.
Treatment group 2: NGF 37ml wrapped in MPC nanomaterials (dose was given as 320 μg/ml) was injected intravenously every week for 12 weeks, including one administration at the starting point for a total of 13 times, as well as maintaining original basic drugs and rehabilitation treatment.
Control group: NGF 60ml (dose was given as 320 μg/ml) was injected intravenously every week for 12 weeks, including one administration at the starting point for a total of 13 times, as well as maintaining original basic drugs and rehabilitation treatment.
Face to face interviews will be made on baseline, 28±4 days after randomization, 84±7 days after randomization and 120±7 days after randomization. Online interviews will be made on 180±14 days and 1 year ±14 days after randomization.
The primary outcome, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores of ALS patients in the treatment group and the control group after 3 months of NGF injection, will be compared by Wilcoxon rank sum test, and β and 95% confidence interval (CI) will be calculated. The survival / mortality of ALS patients in treatment group and control group will be analyzed by COX regression model, and hazard ratio (HR) value and 95%CI were be calculated. Survival curve will be calculated by Nelson-Aalen cumulative risk curve, and Gray's test will be used for comparison between groups.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Nerve Growth Factor
- Keywords
- nerve growth factor, amyotrophic lateral sclerosis, 2-methacryloyloxyethyl phosphorylcholine
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nerve Growth FactorDrug
intravenously injection
| Study group | Role | What they receive |
|---|---|---|
| MPC-NGF T1 | Experimental | 19.2mg MPC wrapped NGF per week for 13 times Receives: Drug: Nerve Growth Factor |
| MPC-NGF T2 | Experimental | 11.84mg MPC wrapped NGF per week for 13 times Receives: Drug: Nerve Growth Factor |
| X-NGF | Active comparator | 19.2mg NGF per week for 13 times Receives: Drug: Nerve Growth Factor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score (ALSFRS-R scores from 0 to 48, score decline indicates worse outcome of ALS patients, or disease progression and disability).
Measured: 84±7 days
Secondary outcomes (7)
Endpoint events
The incidence of endpoint events (survival/mortality, tracheotomy/permanent respiratory, gastrostomy) of ALS patients.
Measured: 28±4 days, 84±7 days, 120±7 days, 180±14 days, 1 year ±14 days
Tolerance
Tolerance of ALS patients during treatment: defined as percentage of subjects able to continue the investigational drug until planned discontinuation
Measured: 28±4 days, 84±7 days
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score (ALSFRS-R scores from 0 to 48, score decline indicates worse outcome of ALS patients, or disease progression and disability).
Measured: 28±4 days, 120±7 days, 180±14 days, 1 year ±14 days
Lung function: forced vital capacity
Forced vital capacity in millilitre of ALS patients. Value decline indicates worse outcome of ALS patients, or disease progression and disability.
Measured: 28±4 days, 84±7 days, 120±7 days
Lung function: slow vital capacity
Slow vital capacity in millilitre of ALS patients. Value decline indicates worse outcome of ALS patients, or disease progression and disability.
Measured: 28±4 days, 84±7 days, 120±7 days
Lung function: transcutaneous oxygen saturation
Transcutaneous oxygen saturation in % of ALS patients. Value decline indicates worse outcome of ALS patients, or disease progression and disability.
Measured: 28±4 days, 84±7 days, 120±7 days
Muscle involvement
Muscle involvement will be assessed by needle electromyography, which analyzes muscle damage qualitatively based on spontaneous, motor unit action potential and recruitment. More muscle involvement indicates worse outcome of ALS patients, or disease progression and disability.
Measured: 120±7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2024
- Study startMay 2024 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing University of Chemical Technology, Beijing Healthunion Cardio-Cerebrovascular Disease Prevention and Treatment Foundation
- Responsible party
- Principal investigator, yilong Wang, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06391645
- Sponsor's protocol ID
- HX-A-2023027
- Acronym
- NATURAL
- Status last verified
- Apr 2024
- First submitted
- 8 Mar 2024
- Last updated
- 30 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nerve Growth Factor Encapsulated With 2-methacryloyloxyethyl Phosphorylcholine Nanocapsules in the Treatment of Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT06391645
- Acronym / sponsor ID
- NATURAL / HX-A-2023027
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- nerve growth factor, amyotrophic lateral sclerosis, 2-methacryloyloxyethyl phosphorylcholine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Collaborators
- Beijing University of Chemical Technology, Beijing Healthunion Cardio-Cerebrovascular Disease Prevention and Treatment Foundation
- Study start
- May 2024 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 30 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.
Amyotrophic lateral sclerosis (ALS) is one of the most lethal neurodegenerative diseases, with most patients dying from respiratory failure 3-5 years after the onset. The purpose of this study is to explore the efficacy and safety of nerve growth factor (NGF) encapsulated with 2-methacryloyloxyethyl phosphorylcholine (MPC) nanocapsules in the treatment of ALS patients.
Detailed description
Amyotrophic lateral sclerosis (ALS) is one of the most lethal neurodegenerative diseases. Most patients die due to respiratory failure 3-5 years after disease onset. Due to the low permeability and blocking of the blood-brain barrier (BBB) on more than 95% of all kinds of drugs, the drug treatment of ALS is relatively limited. Although a series of studies have been carried out on new therapies to ALS, such as monoclonal antibodies represented by ozanezumab and antisense oligonucleotides represented by tofersen, the conclusions are mostly limited to safety evaluation.
Nerve growth factor (NGF) provides protection and/or regeneration for neurons in the peripheral and central nervous system (CNS), which is considered to be a nerve regeneration agent with great therapeutic potential. The phase I clinical trial of intravenous recombinant human nerve growth factor (rhNGF) showed that, on the premise of ensuring safety, only a trace of NGF (3.6-7.38 ng/ml within 5 minutes) was detected in the plasma samples of the subjects who were injected with rhNGF 1.0 μg/kg (the maximum dose of this trial design).
In purpose of improving the therapeutic effect of NGF, the investigators plan to encapsulate NGF in nanoparticles linked by 2-methacryloyloxyethyl phosphorylcholine (MPC), consisting of one molecule of choline and one molecule of acetylcholine analog. After intravenous administration, the drug particles are effectively delivered to the CNS via receptor-mediated transcytosis (RMT) with the help of acetylcholine transporter and choline transporter widely expressed on brain capillary endothelial cells. The animal experiments have confirmed that intravenous injection of MPC encapsulated NGF capsule [n(NGF)] can effectively prolong the survival time of SOD1G93A mice, reduce the body weight loss and delay the time of dyskinesia onset compared with NGF. Similar results were obtained in the rhesus monkey model.
The purpose of this study is to explore the efficacy and safety of NGF encapsulated with MPC nanocapsules in the treatment of ALS patients.
This is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. The trial planned to enroll 60 ALS patients, aged 18-80 years, with disease duration 6 months to 3 years, with forced vital capacity (FVC) ≥ 85% of predicted value.
Patients will be randomly assigned to one of the following 3 groups at 1:1 ratio.
Treatment group 1: NGF 60ml wrapped in MPC nanomaterials (dose was given as 320 μg/ml) was injected intravenously every week for 12 weeks, including one administration at the starting point for a total of 13 times, as well as maintaining original basic drugs and rehabilitation treatment.
Treatment group 2: NGF 37ml wrapped in MPC nanomaterials (dose was given as 320 μg/ml) was injected intravenously every week for 12 weeks, including one administration at the starting point for a total of 13 times, as well as maintaining original basic drugs and rehabilitation treatment.
Control group: NGF 60ml (dose was given as 320 μg/ml) was injected intravenously every week for 12 weeks, including one administration at the starting point for a total of 13 times, as well as maintaining original basic drugs and rehabilitation treatment.
Face to face interviews will be made on baseline, 28±4 days after randomization, 84±7 days after randomization and 120±7 days after randomization. Online interviews will be made on 180±14 days and 1 year ±14 days after randomization.
The primary outcome, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores of ALS patients in the treatment group and the control group after 3 months of NGF injection, will be compared by Wilcoxon rank sum test, and β and 95% confidence interval (CI) will be calculated. The survival / mortality of ALS patients in treatment group and control group will be analyzed by COX regression model, and hazard ratio (HR) value and 95%CI were be calculated. Survival curve will be calculated by Nelson-Aalen cumulative risk curve, and Gray's test will be used for comparison between groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MPC-NGF T1 | Experimental | Drug: Nerve Growth Factor19.2mg MPC wrapped NGF per week for 13 times |
| MPC-NGF T2 | Experimental | Drug: Nerve Growth Factor11.84mg MPC wrapped NGF per week for 13 times |
| X-NGF | Active comparator | Drug: Nerve Growth Factor19.2mg NGF per week for 13 times |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18-80 years old;
- Confirmed or possible familial or sporadic ALS diagnosed according to the revised El Escorial criteria;
- 6 months ≤disease duration ≤ 3 years, (onset time is defined as the time of the first occurrence of myasthenia);
- Forced vital capacity (FVC) ≥ 85% of predicted value (based on gender, height and age);
- Informed consent signed.
Key exclusion criteria (13 listed)
- Patients undergoing endotracheal intubation, non-invasive or mechanical ventilation;
- Patients with diaphragmatic pacemakers;
- Allergy to any component of the investigational medication, or any other allergic history that researchers deem necessary to be vigilant about;
- Local skin infection or other suspicious signs of infection at the injection site;
- Known hemorrhagic tendency (including but not limited to: platelet count \<100×109/ L; on therapy of heparin, activated partial thromboplastin time (APTT) ≥35s; on therapy of warfarin, international normalized ratio (INR) >1.7; on therapy of novel oral anticoagulants; with direct thrombin or factor Xa inhibitor; accompanied with coagulopathy such as hemophilia);
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 |
|---|---|---|
| Nerve Growth Factorintravenously injection | Drug | MPC-NGF T1, MPC-NGF T2, X-NGF |
Primary outcome
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Time frame: 84±7 days
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score (ALSFRS-R scores from 0 to 48, score decline indicates worse outcome of ALS patients, or disease progression and disability).
7 secondary outcomes
Endpoint events
Time frame: 28±4 days, 84±7 days, 120±7 days, 180±14 days, 1 year ±14 days
Tolerance
Time frame: 28±4 days, 84±7 days
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Time frame: 28±4 days, 120±7 days, 180±14 days, 1 year ±14 days
Lung function: forced vital capacity
Time frame: 28±4 days, 84±7 days, 120±7 days
Lung function: slow vital capacity
Time frame: 28±4 days, 84±7 days, 120±7 days
Lung function: transcutaneous oxygen saturation
Time frame: 28±4 days, 84±7 days, 120±7 days
Muscle involvement
Time frame: 120±7 days
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 30 Apr 2024.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Nerve Growth Factor in people with Amyotrophic Lateral Sclerosis, run by Beijing Tiantan Hospital.
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 5 inclusion and 13 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: opening soon, as of the sponsor's last update on 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Xinru Liu (13521588395, liuxinru0826@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) (time frame: 84±7 days). 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 30 Apr 2024.