RetinoblastomaEarly Phase 1NCT06424301
Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma
A Early Phase 1 study testing Targeting NUDT21 siRNA drugs in people with Retinoblastoma and Refractory, run by Eye & ENT Hospital of Fudan University at 1 site in China.
Trial summary
Retinoblastoma (RB) is the most common intraocular malignancy in children, accounting for approximately 11% of all cancers diagnosed in children under the age of one. Although its incidence is relatively low-about 1 in 15,000 to 20,000 live births-RB has a high risk of intracranial metastasis via the optic nerve… Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Retinoblastoma, Refractory
- What is being tested?
- Targeting NUDT21 siRNA drugs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteChina
- Study dates
- 20 Dec 2024to 30 Sep 2025
- 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with retinoblastoma with a somatic mutation of the gene RB1 and active tumor in a single eye, or germinal mutation of RB1 with active tumor/s in an eye and the contralateral eye unaffected, enucleated or without tumor activity. In both cases, relapsed or refractory with the use of systemic, intraarterial or intravitreal chemotherapy or radiotherapy, in accordance with the availability at his/her referral site, in whom enucleation is the only recommended treatment under opinion of the medical team treating the case at the originating referral site. But the patient has a strong desire to preserve the eye.
- Normal renal function: serum creatinine: < 45 μmol/L (0-2 years); < 57 μmol/L (3-6 years); < 60 μmol/L (7-10 years); < 80 μmol/L (11-13 years).
- Normal Hepatic function: serum ALT: < 0,52 μkat/L (de 9 months -12 years); serum AST: 61-80 g/L (8 months - 5 years); 63-83 g/L (5-9 years); 63-82 g/L (9-12 years).
- Age greater than 6 months at the time of inclusion in the study.
- Sign the informed consent form and be willing to follow up at the specified time.
Who cannot join
- Presence of factors that require immediate enucleation of the affected eye such as glaucoma, rubeosis iridis, anterior chamber involvement.
- Comorbidities: Uncontrolled epilepsy with anticonvulsant treatment, cardiac disease not compensated by treatment.
- Active Infections.
- Other chronic or active acute diseases that under the criterion of the researcher were an exclusion criterion.
- History of having received attenuated or live vaccines in the 30 days prior to inclusion in the study.
- Any cause of Immunosuppression.
Show all 10Show fewer
- Trilateral Retinoblastoma.
- Extraocular spread.
- History of having received treatment for retinoblastoma with chemotherapy or radiation therapy by any means within 30 days prior to inclusion in the study.
- Patients who can not complete the study procedures.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Ruiqi Ma, MD contact
China1 site, 1 recruiting
- Recruiting
Fudan Eye & ENT Hospital
Shanghai
Ruiqi Ma, +86 (021) 64377134, ruiqi_ma@fudan.edu.cn
About this study
Official title: Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma (A Prospective Pilot Study)
Retinoblastoma (RB) is the most common intraocular malignancy in children, accounting for approximately 11% of all cancers diagnosed in children under the age of one. Although its incidence is relatively low-about 1 in 15,000 to 20,000 live births-RB has a high risk of intracranial metastasis via the optic nerve, often leading to poor prognosis in advanced cases.
Recent advances in administration routes, such as intravitreal and intra-arterial chemotherapy, have significantly improved eye preservation rates. However, these strategies are limited by cumulative retinal toxicity and drug resistance. In refractory cases, enucleation remains the only definitive treatment to prevent extraocular spread and death.
Read more
In light of these challenges, current research efforts are focused on developing novel targeted therapies that enhance anti-tumor efficacy while minimizing local toxicity. In this context, we introduce a first-in-class siRNA-based drug targeting NUDT21, which promotes tumor regression by modulating the 3'UTR tail of SMC1A, thereby suppressing tumor cell proliferation. Importantly, the siRNA drug selectively targets tumor cells, offering a favorable safety profile compared to conventional chemotherapeutic regimens.
Given that both the target (NUDT21) and the mode of administration (intraocular siRNA injection) are novel in retinoblastoma treatment, there is an urgent need for early-phase investigator-initiated clinical research. This study is therefore designed to assess the short-term safety and preliminary efficacy of NUDT21 siRNA in patients with refractory retinoblastoma, and to provide an evidence base for future large-scale clinical trials.
- Conditions
- Retinoblastoma, Refractory
- Being tested
- Targeting NUDT21 siRNA drugs
- Keywords
- retinoblastoma, intravitreal Chemotherapy
- Medical subject headings
- Retinoblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeting NUDT21 siRNA drugsDrug
It is performed for intravitreal chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Intravitreal chemotherapy in patients with refractory retinoblastoma | Experimental | Prior to the first administration of the targeted drug, enrolled patients underwent peripheral blood sampling and comprehensive clinical evaluation. Intravitreal injections of the targeted drug were administered at a dosage of 100-200 μg (100 μg for patients under 2 years of age; 200 μg for patients aged 2 years and above) on Day 1 of Weeks 1, 3, and 7. Aqueous humor samples were collected at the time of injection during Weeks 1, 3, and 7. Clinical assessments were conducted monthly, with continuous follow-up extending through Week 24. Receives: Drug: Targeting NUDT21 siRNA drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any unfavorable or unintended sign, symptom, or disease temporally associated with the administration of intravitreal siRNA therapy, whether or not considered related to the drug. Use CTCAE v5.0 (Common Terminology Criteria for Adverse Events) for grading severity.
Measured: 6 months
Secondary outcomes (3)
Tumor size
Tumor size will be assessed by measuring tumor thickness (height) from the retinal surface to the apex of the lesion on optical coherence tomography (OCT) scan. Serial OCT scans will be used to track tumor regression or progression over time. This outcome aims to assess anatomical response to treatment and provide imaging-based evidence of therapeutic efficacy.
Measured: 6 months
Retinal function
Photopic flicker electroretinography (ERG) will be conducted in accordance with ISCEV standards, typically using a 30 Hz stimulus. The amplitude will be measured and compared pre- and post-treatment. This outcome will assess the potential impact of the investigational therapy on cone system integrity and retinal functional preservation.
Measured: 6 months
Target engagement
We will measure the concentrations of NUDT21 and SMC1A proteins in aqueous humor samples using enzyme-linked immunosorbent assay (ELISA) before and after treatment. This assessment will confirm pharmacodynamic target engagement of the NUDT21 siRNA therapy by evaluating changes in NUDT21 and downstream effector SMC1A expression levels.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2024
- Study start20 Dec 2024
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RetinoblastomaStudies of the same condition, open and under way.
- More trials run by Eye & ENT Hospital of Fudan UniversityThe 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
- 2 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eye & ENT Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- The Eye Hospital of Wenzhou Medical University
- Responsible party
- Sponsor
- Investigators
- Chen Zhao, MD, Principal investigator, Fudan Eye & ENT HospitalKang Xue, MD, Study director, Fudan Eye & ENT HospitalKang Zhang, MD, Study director, The Eye Hospital of Wenzhou Medical UniversityJiang Qian, MD, Study director, Fudan Eye & ENT Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06424301
- Sponsor's protocol ID
- FDEENT-20241031
- Status last verified
- Jun 2025
- First submitted
- 16 May 2024
- Last updated
- 26 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared upon requirement.
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma (A Prospective Pilot Study)
- ClinicalTrials.gov ID
- NCT06424301
- Acronym / sponsor ID
- FDEENT-20241031
- Conditions
- Retinoblastoma, Refractory
- Keywords
- retinoblastoma, intravitreal Chemotherapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2 participants (estimated)
- Lead sponsor
- Eye & ENT Hospital of Fudan UniversityUniversity, hospital or other
- Collaborators
- The Eye Hospital of Wenzhou Medical University
- Study start
- 20 Dec 2024 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 22 May 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.
Retinoblastoma (RB) is the most common intraocular malignancy in children, accounting for approximately 11% of all cancers diagnosed in children under the age of one. Although its incidence is relatively low-about 1 in 15,000 to 20,000 live births-RB has a high risk of intracranial metastasis via the optic nerve, often leading to poor prognosis in advanced cases.
Recent advances in administration routes, such as intravitreal and intra-arterial chemotherapy, have significantly improved eye preservation rates. However, these strategies are limited by cumulative retinal toxicity and drug resistance. In refractory cases, enucleation remains the only definitive treatment to prevent extraocular spread and death.
In light of these challenges, current research efforts are focused on developing novel targeted therapies that enhance anti-tumor efficacy while minimizing local toxicity. In this context, we introduce a first-in-class siRNA-based drug targeting NUDT21, which promotes tumor regression by modulating the 3'UTR tail of SMC1A, thereby suppressing tumor cell proliferation. Importantly, the siRNA drug selectively targets tumor cells, offering a favorable safety profile compared to conventional chemotherapeutic regimens.
Given that both the target (NUDT21) and the mode of administration (intraocular siRNA injection) are novel in retinoblastoma treatment, there is an urgent need for early-phase investigator-initiated clinical research. This study is therefore designed to assess the short-term safety and preliminary efficacy of NUDT21 siRNA in patients with refractory retinoblastoma, and to provide an evidence base for future large-scale clinical trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intravitreal chemotherapy in patients with refractory retinoblastoma | Experimental | Drug: Targeting NUDT21 siRNA drugsPrior to the first administration of the targeted drug, enrolled patients underwent peripheral blood sampling and comprehensive clinical evaluation. Intravitreal injections of the targeted drug were administered at a dosage of 100-200 μg (100 μg for patients under 2 years of age; 200 μg for patients aged 2 years and above) on Day 1 of Weeks 1, 3, and 7. Aqueous humor samples were collected at the time of injection during Weeks 1, 3, and 7. Clinical assessments were conducted monthly, with continuous follow-up extending through Week 24. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with retinoblastoma with a somatic mutation of the gene RB1 and active tumor in a single eye, or germinal mutation of RB1 with active tumor/s in an eye and the contralateral eye unaffected, enucleated or without tumor activity. In both cases, relapsed or refractory with the use of systemic, intraarterial or intravitreal chemotherapy or radiotherapy, in accordance with the availability at his/her referral site, in whom enucleation is the only recommended treatment under opinion of the medical team treating the case at the originating referral site. But the patient has a strong desire to preserve the eye.
- Normal renal function: serum creatinine: < 45 μmol/L (0-2 years); < 57 μmol/L (3-6 years); < 60 μmol/L (7-10 years); < 80 μmol/L (11-13 years).
- Normal Hepatic function: serum ALT: < 0,52 μkat/L (de 9 months -12 years); serum AST: 61-80 g/L (8 months - 5 years); 63-83 g/L (5-9 years); 63-82 g/L (9-12 years).
- Age greater than 6 months at the time of inclusion in the study.
- Sign the informed consent form and be willing to follow up at the specified time.
Key exclusion criteria (10 listed)
- Presence of factors that require immediate enucleation of the affected eye such as glaucoma, rubeosis iridis, anterior chamber involvement.
- Comorbidities: Uncontrolled epilepsy with anticonvulsant treatment, cardiac disease not compensated by treatment.
- Active Infections.
- Other chronic or active acute diseases that under the criterion of the researcher were an exclusion criterion.
- History of having received attenuated or live vaccines in the 30 days prior to inclusion in the study.
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 |
|---|---|---|
| Targeting NUDT21 siRNA drugsIt is performed for intravitreal chemotherapy. | Drug | Intravitreal chemotherapy in patients with refractory retinoblastoma |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 6 months
Treatment-emergent adverse events (TEAEs) are defined as any unfavorable or unintended sign, symptom, or disease temporally associated with the administration of intravitreal siRNA therapy, whether or not considered related to the drug. Use CTCAE v5.0 (Common Terminology Criteria for Adverse Events) for grading severity.
3 secondary outcomes
Tumor size
Time frame: 6 months
Retinal function
Time frame: 6 months
Target engagement
Time frame: 6 months
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 26 Jun 2025.
- Individual participant dataSharing planned: Yes. IPD will be shared upon requirement.
Related trials for Retinoblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (Gemcitabine) for Soft Tissue Sarcoma
Advanced Dedifferentiated Liposarcoma, Advanced Leiomyosarcoma
RecruitingObservational study
Comprehensive Omics Analysis of Pediatric and Adult Solid Tumors and Establishment of a Repository for Related Biological Studies
Sarcoma, Endocrine Tumors
Active, not recruitingPhase 1
EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
Pediatric Solid Tumor, Germ Cell Tumor
Enrolling by invitationObservational study
Effect of Treatment Modality on Psychosocial Functioning of Survivors of Unilateral Retinoblastoma
Survivors of Unilateral Retinoblastoma
Active, not recruitingPhase 1
Safety/Efficacy Study of CID-078 in Patients With Advanced Solid Tumor Malignancies
Advanced Solid Tumor, Metastatic Solid Tumor
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.
Ruiqi Ma, MD contact
Chen Zhao, MD principal investigator
Fudan Eye & ENT Hospital
Kang Xue, MD study director
Fudan Eye & ENT Hospital
Kang Zhang, MD study director
The Eye Hospital of Wenzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Targeting NUDT21 siRNA drugs in people with Retinoblastoma and Refractory, run by Eye & ENT Hospital of Fudan University at 1 site in China.
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 10 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: looking for participants now, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 Chen Zhao, MD (86-021-64377134, dr_zhaochen@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: 6 months). 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 26 Jun 2025.