Amyotrophic Lateral Sclerosis (ALS)Early Phase 1RAG-21-FUS-ALSNCT07080801
Study on the Safety and Efficacy of RAG-21 in the Treatment of Amyotrophic Lateral Sclerosis Patients With FUS Gene Mutations
A Early Phase 1 study testing RAG-21 in people with Amyotrophic Lateral Sclerosis (ALS), run by Beijing Tiantan Hospital.
Trial summary
Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative disease that remains incurable, with limited existing therapies or drugs available. Familial ALS can be caused by mutations in various genes. In Asia, mutations in the FUS gene are relatively common among early-onset familial ALS patients. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis (ALS)
- What is being tested?
- RAG-21
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- No sites listed yet
- Study dates
- Aug 2025to Dec 2026
- Phase
- Early Phase 1
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years, gender unlimited.
- Clearly identify amyotrophic lateral sclerosis (ALS) patients with FUS gene mutations (known FUS mutation sites and reported disease progression).
- Forced vital capacity (FVC) during screening period ≥ 50% of expected lung capacity.
- ALS patients diagnosed according to the Gold Coast criteria (2020) with limb-onset weakness.
- The patient or their legal representative clearly understands and voluntarily participates in the study and signs an informed consent form.
- The subjects (including male subjects) have no family planning throughout the entire study and within 3 months after, voluntarily take effective contraceptive measures and without any plans to donate sperm or ovum.
Who cannot join
- FUS mutation sites located within nucleotides 928-970 (calculated from the translation of FUS protein).
- Patients who have previously received or are currently receiving Ulefnersen treatment.
- Human immunodeficiency virus (HIV) test positive or positive test history.
- Patients with active hepatitis C or hepatitis B infection.
- Other experimental drugs used within one month or within five drug half-lives.
- Lumbar diseases and deformities.
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- ALS with bulbar-onset symptoms, or suffering from other diseases known to be related to motor neuron dysfunction, which may confuse or blur the diagnosis of ALS.
- Other psychiatric disorders diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria, or obvious suicidal intentions.
- Combined with severe liver dysfunction, renal dysfunction, or severe heart dysfunction (severe liver dysfunction refers to alanine aminotransferase (ALT) value ≥ 2.0 times the upper limit of normal value or aspartate aminotransferase (AST) value ≥ 2.0 times the upper limit of normal value; severe renal dysfunction refers to creatinine (CRE) ≥ 1.5 times the upper limit of normal value or estimated glomerular filtration rate (eGFR) < 40mL/min/1.73m^2; severe heart dysfunction refers to New York College of Cardiology (NYHA) 3-4 levels).
- Permanent and sustained dependence on ventilator assisted ventilation.
- History of combined alcohol and drug abuse.
- Pregnant, lactating, or potentially pregnant patients, as well as those planning to conceive.
- Patients participating in other clinical trials or applying other biologics, drugs, or devices under study.
- Patients who have received any vaccination within 28 days.
- Those who can't complete follow-up due to other reasons.
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 a chronic progressive neurodegenerative disease that remains incurable, with limited existing therapies or drugs available. Familial ALS can be caused by mutations in various genes. In Asia, mutations in the FUS gene are relatively common among early-onset familial ALS patients. Reducing the levels of toxic FUS protein may be an effective therapeutic approach for such ALS patients without causing side effects.
RAG-21 is a small interfering ribonucleic acid (siRNA) with a molecular weight of 20 kDa. Through the RNA interference mechanism, it targets the FUS gene, recognizes the corresponding mRNA, and mediates its degradation, thereby downregulating FUS gene expression and reducing toxic FUS protein levels. Accordingly, this project plans to conduct a single-center, dose-escalation clinical study aimed at evaluating the safety, tolerability, and pharmacokinetics of intrathecal bolus administration of RAG-21 in ALS patients carrying FUS gene mutations.
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Being tested
- RAG-21
- Keywords
- RAG-21, FUS gene mutations
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAG-21Drug
Intrathecal bolus administration of RAG-21 will be initiated at a dose of 120 mg, prepared with a dedicated solvent into a 10 mL sterile aqueous solution. Dosing will occur every 2 weeks, with the dose escalating to 180 mg after 3 administrations. Subsequently, the dosing interval will be extended to every 4 weeks. The investigator will then select an optimal dose from the completed dose cohorts or continue dose escalation until the maximum tolerated dose (MTD) is reached, with a predefined maximum dose of 210 mg. For continued treatment, the investigator-determined optimal dose will be administered as a fixed dose every 4 weeks, with a total treatment duration of 6 months (8 administrations).
| Study group | Role | What they receive |
|---|---|---|
| RAG-21 | Experimental | Not described Receives: Drug: RAG-21 |
What is being measured
The primary outcome is the main question the study is designed to answer.
AE&SAE
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) after RAG-21 treatment.
Measured: 15±1, 29±2, 57±3, 85±3, 113±3, 141±3, 169±3, 197±7days after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study startAug 2025 (estimated)
- Primary completionAug 2026 (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 Sclerosis (ALS)Studies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, yilong Wang, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07080801
- Sponsor's protocol ID
- HX-A-2025021
- Acronym
- RAG-21-FUS-ALS
- Status last verified
- Jul 2025
- First submitted
- 6 Jul 2025
- Last updated
- 23 Jul 2025
- 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 23 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on the Safety and Efficacy of RAG-21 in the Treatment of Amyotrophic Lateral Sclerosis Patients With FUS Gene Mutations
- ClinicalTrials.gov ID
- NCT07080801
- Acronym / sponsor ID
- RAG-21-FUS-ALS / HX-A-2025021
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Keywords
- RAG-21, FUS gene mutations
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- Aug 2025 (estimated)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 23 Jul 2025 (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 a chronic progressive neurodegenerative disease that remains incurable, with limited existing therapies or drugs available. Familial ALS can be caused by mutations in various genes. In Asia, mutations in the FUS gene are relatively common among early-onset familial ALS patients. Reducing the levels of toxic FUS protein may be an effective therapeutic approach for such ALS patients without causing side effects.
RAG-21 is a small interfering ribonucleic acid (siRNA) with a molecular weight of 20 kDa. Through the RNA interference mechanism, it targets the FUS gene, recognizes the corresponding mRNA, and mediates its degradation, thereby downregulating FUS gene expression and reducing toxic FUS protein levels. Accordingly, this project plans to conduct a single-center, dose-escalation clinical study aimed at evaluating the safety, tolerability, and pharmacokinetics of intrathecal bolus administration of RAG-21 in ALS patients carrying FUS gene mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAG-21 | Experimental | Drug: RAG-21 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18-75 years, gender unlimited.
- Clearly identify amyotrophic lateral sclerosis (ALS) patients with FUS gene mutations (known FUS mutation sites and reported disease progression).
- Forced vital capacity (FVC) during screening period ≥ 50% of expected lung capacity.
- ALS patients diagnosed according to the Gold Coast criteria (2020) with limb-onset weakness.
- The patient or their legal representative clearly understands and voluntarily participates in the study and signs an informed consent form.
Key exclusion criteria (15 listed)
- FUS mutation sites located within nucleotides 928-970 (calculated from the translation of FUS protein).
- Patients who have previously received or are currently receiving Ulefnersen treatment.
- Human immunodeficiency virus (HIV) test positive or positive test history.
- Patients with active hepatitis C or hepatitis B infection.
- Other experimental drugs used within one month or within five drug half-lives.
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 |
|---|---|---|
| RAG-21Intrathecal bolus administration of RAG-21 will be initiated at a dose of 120 mg, prepared with a dedicated solvent into a 10 mL sterile aqueous solution. Dosing will occur every 2 weeks, with the dose escalating to 180 mg after 3 administrations. Subsequently, the dosing interval will be extended to every 4 weeks. The investigator will then select an optimal dose from the completed dose cohorts or continue dose escalation until the maximum tolerated dose (MTD) is reached, with a predefined maximum dose of 210 mg. For continued treatment, the investigator-determined optimal dose will be administered as a fixed dose every 4 weeks, with a total treatment duration of 6 months (8 administrations). | Drug | RAG-21 |
Primary outcome
AE&SAE
Time frame: 15±1, 29±2, 57±3, 85±3, 113±3, 141±3, 169±3, 197±7days after treatment
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) after RAG-21 treatment.
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 23 Jul 2025.
- 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 Early Phase 1 study testing RAG-21 in people with Amyotrophic Lateral Sclerosis (ALS), 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 6 inclusion and 15 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 23 Jul 2025. 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
AE&SAE (time frame: 15±1, 29±2, 57±3, 85±3, 113±3, 141±3, 169±3, 197±7days after treatment). 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 23 Jul 2025.