MECP2 Duplication SyndromeHERONCT06615206
A First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of a Novel CRISPR RNA-editing Therapy in Patients with Mecp2 Duplication Syndrome, a Rare Orphan Disease (HERO)
A study testing HG204 in people with MECP2 Duplication Syndrome, run by HuidaGene Therapeutics Co., Ltd. at 1 site in China.
Trial summary
Methyl-CpG binding protein 2 (MECP2) is a dosage-sensitive, X-linked gene critical for central nervous system development and functional maintenance, which gain-of-function causes MECP2 duplication syndrome (MDS). Read more about this study
- Who is it for?
- Ages 2 to 18 years, men only
- Conditions the study is for
- MECP2 Duplication Syndrome
- What is being tested?
- HG204
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 30 Oct 2024to 31 Oct 2026
- Phase
- Interventional
- 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 2 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Males ≥ 2 and ≤18 years at the time of signing informed consent;
- Genetic test and clinical confirmed diagnosis of MDS;
- Stable pattern of seizures, or has had no seizures while currently receiving medical treatment (including antiepileptics) and physical therapy are stable for at least 2 months before screening;
- Willing to adhere to protocol, including biological samples collection and hospitalization for intracerebroventricular injection surgery;
- Acceptable hematology, clinical chemistry, and urine laboratory parameters.
Who cannot join
- MECP2 gene triplication;
- Concurrent genetic syndromes other than MDS;
- Significant brain or cerebellar atrophy, or other significant degenerative changes as shown in cranial MRI at screening;
- Prior or current hypertension, cardiomyopathy, myocardial ischemia or atrial fibrillation and other cardiovascular diseases;
- Prior central nervous system surgery within 6 months before enrolment;
- Systemic use of immunosuppressive drugs within 3 months before enrolment;
- Prior gene therapy or oligonucleotide therapy treatments;
- Any other conditions that would not allow the potential subject to complete follow-up examinations during the study and would, in the opinion of the investigator, make the potential subject unsuitable for the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking University First Hospital
Beijing, Beijing Municipality
Study Director, HG20401@huidagene.com
About this study
Official title: An Open-label, Multiple-dose Clinical Study to Evaluating the Safety, Tolerability and Preliminary Efficacy of a Single Intracerebroventricular Injection of HG204 for the Treatment of MECP2 Duplication Syndrome
Methyl-CpG binding protein 2 (MECP2) is a dosage-sensitive, X-linked gene critical for central nervous system development and functional maintenance, which gain-of-function causes MECP2 duplication syndrome (MDS). Affecting primarily in males, this disorder is characterized by severe intellectual disability, motor dysfunction, infantile hypotonia, epilepsy, respiratory tract infections, and premature death before 25 years of age with no curative therapy.
HG204 is a CRISPR RNA-editing therapy packaging novel high-fidelity Cas13Y (hfCas13Y) technology, using one single adeno-associated virus (AAV) vector to target and knock down MECP2 mRNA in the brain. Preclinical studies showed that a single intracerebroventricular injection of HG204 persistently decreased MECP2 mRNA and MECP2 protein in the cortex of the MDS mice, reversed the abnormal motor and social phenotypes, and significantly prolonged survival in MDS mouse models.
- Conditions
- MECP2 Duplication Syndrome
- Being tested
- HG204
- Keywords
- MECP2, dupMECP2, CNS, neurodevelopmental disease, Gene-editing, HG204, CRISPR, MDS
- Medical subject headings
- Lubs X-linked mental retardation syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HG204Genetic
The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose
| Study group | Role | What they receive |
|---|---|---|
| HG204 | Experimental | Once intracerebroventricular injection; The duration of the study is about 60 weeks for each subject, including a 8 weeks screening period, enrollment visit, treatment visit and 52 weeks follow-up period. Receives: Genetic: HG204 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of systemic adverse events
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Measured: 52 weeks
Secondary outcomes (5)
Change from baseline in Clinical Global Impression Scale
Clinical Global Impression Scale is a scale to evaluate mental disorder severity, with a score range from 1-7, the higher scrore means worse mental disorder.
Measured: 52 weeks
Change from baseline in Griffiths Developmental Assessment Scale
Griffiths Developmental Assessment Scale is a scale to evaluate mental development function of children aged 0-8, including sensory, cognitive and movement, the minimum score is 0, and no maximum limit for the highest score, the higher score means better mental development.
Measured: 52 weeks
Change from baseline in Peabody Developmental Assessment Scale
Peabody Developmental Assessment Scale is a scale to evaluate motor function of children aged 0-6, with a score range from 0-100, the higher scrore means better motor function.
Measured: 52 weeks
Change from baseline in Wechsler (toddler/child) Intelligence Scale (fourth version) score
Wechsler (toddler/child) Intelligence Scale (fourth version) score is a scale to assessing the intelligence of children aged 6 to 16, the score range showed a normal distribution, there is no minimum and maximum score, score from 90 to 110 points is normal intelligence result, the higher score means better intelligence.
Measured: 52 weeks
Adaptive Behavior Rating Scale
Adaptive Behavior Rating Scale is a scale assessing daily living ability of children aged 0-18, with a score range from 0-200, the higher score means better daily living ability
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2024
- Study start30 Oct 2024
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MECP2 Duplication SyndromeStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label, multiple doses of a single intracerebroventricular injection of HG204
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- HuidaGene Therapeutics Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Peking University First Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06615206
- Sponsor's protocol ID
- HG20401
- Acronym
- HERO
- Status last verified
- Nov 2024
- First submitted
- 4 Sep 2024
- Last updated
- 26 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- 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 26 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multiple-dose Clinical Study to Evaluating the Safety, Tolerability and Preliminary Efficacy of a Single Intracerebroventricular Injection of HG204 for the Treatment of MECP2 Duplication Syndrome
- ClinicalTrials.gov ID
- NCT06615206
- Acronym / sponsor ID
- HERO / HG20401
- Conditions
- MECP2 Duplication Syndrome
- Keywords
- MECP2, dupMECP2, CNS, neurodevelopmental disease, Gene-editing, HG204, CRISPR, MDS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- HuidaGene Therapeutics Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Peking University First Hospital
- Study start
- 30 Oct 2024 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 26 Sep 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.
Methyl-CpG binding protein 2 (MECP2) is a dosage-sensitive, X-linked gene critical for central nervous system development and functional maintenance, which gain-of-function causes MECP2 duplication syndrome (MDS). Affecting primarily in males, this disorder is characterized by severe intellectual disability, motor dysfunction, infantile hypotonia, epilepsy, respiratory tract infections, and premature death before 25 years of age with no curative therapy.
HG204 is a CRISPR RNA-editing therapy packaging novel high-fidelity Cas13Y (hfCas13Y) technology, using one single adeno-associated virus (AAV) vector to target and knock down MECP2 mRNA in the brain. Preclinical studies showed that a single intracerebroventricular injection of HG204 persistently decreased MECP2 mRNA and MECP2 protein in the cortex of the MDS mice, reversed the abnormal motor and social phenotypes, and significantly prolonged survival in MDS mouse models.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label, multiple doses of a single intracerebroventricular injection of HG204
| Arm | Type | Receives |
|---|---|---|
| HG204 | Experimental | Genetic: HG204Once intracerebroventricular injection; The duration of the study is about 60 weeks for each subject, including a 8 weeks screening period, enrollment visit, treatment visit and 52 weeks follow-up period. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Males ≥ 2 and ≤18 years at the time of signing informed consent;
- Genetic test and clinical confirmed diagnosis of MDS;
- Stable pattern of seizures, or has had no seizures while currently receiving medical treatment (including antiepileptics) and physical therapy are stable for at least 2 months before screening;
- Willing to adhere to protocol, including biological samples collection and hospitalization for intracerebroventricular injection surgery;
- Acceptable hematology, clinical chemistry, and urine laboratory parameters.
Key exclusion criteria (8 listed)
- MECP2 gene triplication;
- Concurrent genetic syndromes other than MDS;
- Significant brain or cerebellar atrophy, or other significant degenerative changes as shown in cranial MRI at screening;
- Prior or current hypertension, cardiomyopathy, myocardial ischemia or atrial fibrillation and other cardiovascular diseases;
- Prior central nervous system surgery within 6 months before enrolment;
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 |
|---|---|---|
| HG204The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose | Genetic | HG204 |
Primary outcome
Incidence and severity of systemic adverse events
Time frame: 52 weeks
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
5 secondary outcomes
Change from baseline in Clinical Global Impression Scale
Time frame: 52 weeks
Change from baseline in Griffiths Developmental Assessment Scale
Time frame: 52 weeks
Change from baseline in Peabody Developmental Assessment Scale
Time frame: 52 weeks
Change from baseline in Wechsler (toddler/child) Intelligence Scale (fourth version) score
Time frame: 52 weeks
Adaptive Behavior Rating Scale
Time frame: 52 weeks
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 Nov 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HG204 in people with MECP2 Duplication Syndrome, run by HuidaGene Therapeutics Co., Ltd. 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 8 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 Nov 2024. 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.
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 Study Director (732-318-9873, HG20401@huidagene.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of systemic adverse events (time frame: 52 weeks). 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 Nov 2024.