Crigler-Najjar SyndromeCareCNNCT03466463
Gene Therapy for Severe Crigler Najjar Syndrome
A study testing GNT0003 in people with Crigler-Najjar Syndrome, run by Genethon at 4 sites in 3 countries.
Trial summary
This is a Phase 1/2, multinational, open-label, study to evaluate the safety and efficacy of an intravenous infusion of GNT0003 in patients with Crigler-Najjar aged ≥10 years and requiring phototherapy. Read more about this study
- Who is it for?
- Ages 9 years and older
- Conditions the study is for
- Crigler-Najjar Syndrome
- What is being tested?
- GNT0003
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 19 Mar 2018to 30 Mar 2030
- 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 9 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with severe Crigler-Najjar syndrome resulting from a molecular confirmation of mutations in the UGT1A1 gene and requiring phototherapy
- Male or female at least 9 years at the date of signature of informed consent
- Patient able to give informed assent and/or consent in writing
Who cannot join
- Patients who underwent liver transplantation
- Patients with chronic hepatitis B or C
- Patients infected with Human immunodeficiency virus (HIV)
- Patients with significant underlying liver disease
- Patients with significant encephalopathy
- Participation in any other investigational trial during this trial
- Patients unable or unwilling to comply with the protocol requirements
Trial locations and contacts
4 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
Genethon Clinical Development Department contact
4 sites in 3 countries
Italy2 sites, 2 recruiting
- Recruiting
ASST Papa Giovanni XXIII
Bergamo, 24127
00390352674959, ldantiga@asst-pg23.it
Lorenzo D'Antiga, MD, PHD
- Recruiting
Azienda Ospedaliera Universitaria Federico II
Naples, 80131
00390816132361, brunetti@tigem.it
Nicola Brunetti-Pierri, MD, PHD
France1 site, 1 recruiting
- Recruiting
Hopital Antoine BECLERE
Clamart, 92141
00 33 (0)1 45 37 42 72, philippe.labrune@abc.aphp.fr
Philippe LABRUNE, MD,PHD
Netherlands1 site, 1 recruiting
- Recruiting
AMC
Amsterdam, 1105
0031-641476782, u.h.beuers@amc.uva.nl
Ulrich Beuers, MD, PHD
About this study
Official title: A Phase I/II, Open Label, Study to Evaluate Safety and Efficacy of an Intravenous Injection of GNT0003 (AAV Vector Expressing the UGT1A1 Transgene) in Patients With Severe Crigler-Najjar Syndrome Requiring Phototherapy
This is a Phase 1/2, multinational, open-label, study to evaluate the safety and efficacy of an intravenous infusion of GNT0003 in patients with Crigler-Najjar aged ≥10 years and requiring phototherapy. Patients will received a single administration of GNT0003 and will be followed for safety and efficacy of approximately 60 months (5 years):
- a follow-up of approximately 12 months (48 weeks)
- a long term follow-up of approximately 48 months (4 years), in order to be in line with the latest EMEA Guideline on follow-up of patients administered with gene therapy medicinal products, released on 22 Oct.2009 by the Committee for medicinal products for human use.
- Conditions
- Crigler-Najjar Syndrome
- Being tested
- GNT0003
- Keywords
- Crigler-Najjar, Adeno Associated Virus
- Medical subject headings
- Crigler-Najjar Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GNT0003Genetic
Intravenous infusion, single dose
| Study group | Role | What they receive |
|---|---|---|
| GNT0003 | Experimental | 2 doses of the IMP assessed in the dose escalation, open-label, phase 1/2 study Receives: Genetic: GNT0003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients having received the selected dose of GNT0003 with serum bilirubin ≤ 300µmol/L within 48 meeks after GNT0003 administration and without phototherapy from week 16
Decrease of total Serum bilirubin level after interruption of daily phototherapy (Efficacy); change in serum total biliirubin from baseline to week 48
Measured: 48 weeks
Incidence of Treatment Emergent Adverse Events or Treatement Serious Adverse Events
Incidence of AE/SAE evaluated by changes in laboratory parameters, vital signs, physical examination, reported from baseline to each visit study. Clinically relevant abnormal findings on Laboratory values, Vital Signs, Physical findings will be reported as Adverse Events.
Incidence and Severity of Adverse Events for each body system will be presented for each dose level and summarized overall.
Measured: 48 weeks
Secondary outcomes (2)
Change in Health-related quality of Life for Adults from Baseline to Week 48 after GNT0003 administration
Quality of Life outcome measure: change of quality of life from Baseline to Week 48 after GNT0003 administration.
Scale 36-Item Short Form Survey (SF-36 Health Survey) for adults: from 0 (negative to health) to 100 (positive to health)
Measured: 48 weeks
Change in Health-related quality of Life for Children from Baseline to Week 48 after GNT0003 administration
Quality of Life outcome measure: change of quality of life from Baseline to Week 48 after GNT0003 administration.
PedsQL 4.0 Generic Core Scale for pediatrics: 0-100 scale where higher scores indicate better health-related quality of life
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2018
- Study start19 Mar 2018
- Primary completion30 Mar 2026 (estimated)
- Study completion30 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crigler-Najjar 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
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 17 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genethon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- LABRUNE Philippe, Prof, Principal investigator, Hopital Antoine Beclere
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03466463
- Sponsor's protocol ID
- GNT-012-CRIG
- Acronym
- CareCN
- Status last verified
- Feb 2023
- First submitted
- 1 Feb 2018
- Last updated
- 28 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
D'Antiga L, Beuers U, Ronzitti G, Brunetti-Pierri N, Baumann U, Di Giorgio A, Aronson S, Hubert A, Romano R, Junge N, Bosma P, Bortolussi G, Muro AF, Soumoudronga RF, Veron P, Collaud F, Knuchel-Legendre N, Labrune P, Mingozzi F. Gene Therapy in Patients with the Crigler-Najjar Syndrome. N Engl J Med. 2023 Aug 17;389(7):620-631. doi: 10.1056/NEJMoa2214084.
PubMed 37585628
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open Label, Study to Evaluate Safety and Efficacy of an Intravenous Injection of GNT0003 (AAV Vector Expressing the UGT1A1 Transgene) in Patients With Severe Crigler-Najjar Syndrome Requiring Phototherapy
- ClinicalTrials.gov ID
- NCT03466463
- Acronym / sponsor ID
- CareCN / GNT-012-CRIG
- Conditions
- Crigler-Najjar Syndrome
- Keywords
- Crigler-Najjar, Adeno Associated Virus
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 17 participants (estimated)
- Lead sponsor
- GenethonUniversity, hospital or other
- Study start
- 19 Mar 2018 (actual)
- Primary completion
- 30 Mar 2026 (estimated)
- Study completion
- 30 Mar 2030 (estimated)
- First posted
- 15 Mar 2018 (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.
This is a Phase 1/2, multinational, open-label, study to evaluate the safety and efficacy of an intravenous infusion of GNT0003 in patients with Crigler-Najjar aged ≥10 years and requiring phototherapy. Patients will received a single administration of GNT0003 and will be followed for safety and efficacy of approximately 60 months (5 years):
- a follow-up of approximately 12 months (48 weeks)
- a long term follow-up of approximately 48 months (4 years), in order to be in line with the latest EMEA Guideline on follow-up of patients administered with gene therapy medicinal products, released on 22 Oct.2009 by the Committee for medicinal products for human use.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GNT0003 | Experimental | Genetic: GNT00032 doses of the IMP assessed in the dose escalation, open-label, phase 1/2 study |
Who may qualify
- Ages
- 9 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with severe Crigler-Najjar syndrome resulting from a molecular confirmation of mutations in the UGT1A1 gene and requiring phototherapy
- Male or female at least 9 years at the date of signature of informed consent
- Patient able to give informed assent and/or consent in writing
Key exclusion criteria (7 listed)
- Patients who underwent liver transplantation
- Patients with chronic hepatitis B or C
- Patients infected with Human immunodeficiency virus (HIV)
- Patients with significant underlying liver disease
- Patients with significant encephalopathy
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 |
|---|---|---|
| GNT0003Intravenous infusion, single dose | Genetic | GNT0003 |
Primary outcome
Proportion of patients having received the selected dose of GNT0003 with serum bilirubin ≤ 300µmol/L within 48 meeks after GNT0003 administration and without phototherapy from week 16
Time frame: 48 weeks
Decrease of total Serum bilirubin level after interruption of daily phototherapy (Efficacy); change in serum total biliirubin from baseline to week 48
Incidence of Treatment Emergent Adverse Events or Treatement Serious Adverse Events
Time frame: 48 weeks
Incidence of AE/SAE evaluated by changes in laboratory parameters, vital signs, physical examination, reported from baseline to each visit study. Clinically relevant abnormal findings on Laboratory values, Vital Signs, Physical findings will be reported as Adverse Events. Incidence and Severity of Adverse Events for each body system will be presented for each dose level and summarized overall.
2 secondary outcomes
Change in Health-related quality of Life for Adults from Baseline to Week 48 after GNT0003 administration
Time frame: 48 weeks
Change in Health-related quality of Life for Children from Baseline to Week 48 after GNT0003 administration
Time frame: 48 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 28 Mar 2023.
- Derived from this study: PubMed 37585628D'Antiga L, Beuers U, Ronzitti G, Brunetti-Pierri N, Baumann U, Di Giorgio A, Aronson S, Hubert A, Romano R, Junge N, Bosma P, Bortolussi G, Muro AF, Soumoudronga RF, Veron P, Collaud F, Knuchel-Legendre N, Labrune P, Mingozzi F. Gene Therapy in Patients with the Crigler-Najjar Syndrome. N Engl J Med. 2023 Aug 17;389(7):620-631. doi: 10.1056/NEJMoa2214084.
Related trials for Crigler-Najjar Syndrome
RecruitingPhase 1/2
Gene Therapy for Crigler Najjar Syndrome Type I (AlphaCN)
Crigler-Najjar Syndrome Type I
RecruitingPhase 2
Efficacy and Safety of GNT0003 Following Imlifidase Pre-treatment in Severe Crigler-Najjar Syndrome
Crigler-Najjar Syndrome
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.
Genethon Clinical Development Department contact
LABRUNE Philippe, Prof principal investigator
Hopital Antoine Beclere
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GNT0003 in people with Crigler-Najjar Syndrome, run by Genethon at 4 sites in 3 countries.
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 3 inclusion and 7 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 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy, France, Netherlands. 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 Genethon Clinical Development Department (00 33 (0)1 69 47 10 32, clinical_development@genethon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients having received the selected dose of GNT0003 with serum bilirubin ≤ 300µmol/L within 48 meeks after GNT0003 administration and without phototherapy from week 16 (time frame: 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03466463, which also lists 1 linked publication.
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 28 Mar 2023.