Crigler-Najjar SyndromePhase 2NCT06518005
Efficacy and Safety of GNT0003 Following Imlifidase Pre-treatment in Severe Crigler-Najjar Syndrome
A Phase 2 study testing Imlifidase and GNT0003 in people with Crigler-Najjar Syndrome, run by Genethon at 1 site in France.
Trial summary
Clinical trial rationale: CNS is an ultra-rare (<1/1 million newborns), autosomal recessive disorder of bilirubin conjugation caused by mutation in the gene coding for uridine 5'-diphosphate glucuronosyltransferase (UGT1A1), that causes the accumulation of neurotoxic unconjugated bilirubin (UCB). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crigler-Najjar Syndrome
- What is being tested?
- Imlifidase and GNT0003
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteFrance
- Study dates
- 8 Nov 2024to 30 Sep 2030
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Participation in another interventional trial within 6 months prior to start of clinical trial intervention and during the whole clinical trial
- Fibrosis score ≥ 3 (METAVIR) or 10 kPa (FibroScan®)
- Liver transplantation
- Significant underlying liver disease, chronic hepatitis B, C and/or infected with Human immunodeficiency virus
- Any other clinically significant illness
- Uncontrolled hyperlipidemia.
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- History of major thrombotic events, active peripheral vascular disease, proven hypercoagulable conditions,
- History or presence of thrombotic thrombocytopenic purpura (TTP) or known familial history of TTP
- Prior or current treatment with Gene therapy, cell based therapy, CRISPR/Cas9 or any other form of gene editing, imlifidase
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
GENETHON Clinical Development Department contact
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
About this study
Official title: An Open-label, Phase 2 Trial to Evaluate the Efficacy and Safety of a Single Intravenous Administration of GNT0003 (an Adeno-associated Viral (AAV) Vector Expressing the UGT1A1 Transgene) Following Imlifidase Pre-treatment in Adult Participants With Severe Crigler-Najjar Syndrome (CNS) Requiring Daily Phototherapy and Presenting Pre-existing Anti-AAV8 Antibodies
Clinical trial rationale:
CNS is an ultra-rare (<1/1 million newborns), autosomal recessive disorder of bilirubin conjugation caused by mutation in the gene coding for uridine 5'-diphosphate glucuronosyltransferase (UGT1A1), that causes the accumulation of neurotoxic unconjugated bilirubin (UCB).
Read more
Reduction of UCB is managed with phenobarbital in mild CNS, and daily phototherapy in severe CNS.
There is no authorized curative medical treatment for CNS. Liver transplantation is currently the only curative treatment for severe CNS.
GNT0003 is a genetically modified recombinant (r) viral vector composed of the AAV8 viral capsid carrying the UGT1A1 transgene which aims to correct the dysfunction of the mutated gene by achieving durable expression of a functional copy of the affected gene.
Imlifidase (IgG-degrading enzyme) has demonstrated its efficacy in highly sensitized adult kidney transplant patients.
To give participants with pre-existing anti-AAV8 antibodies access to gene therapy treatments, this trial aims to demonstrate the safety and efficacy of GNT0003 following imlifidase pre-treatment in adult participants with severe CNS requiring daily phototherapy and presenting with pre-existing anti-AAV8 antibodies.
Primary objective: to assess efficacy of a single intravenous administration of GNT0003 following imlifidase pre-treatment in participants with severe CNS requiring phototherapy and pre-existing AAV8 antibodies
Secondary objective: to collect data on safety and tolerability of GNT0003 and imlifidase, efficacy of imlifidase, pharmacokinetic and pharmacodynamic profile of GNT0003, and Quality of Life.
The trial will include 3 parts:
- A baseline period for at least 3 months
- A treatment period
- A follow-up period:
- Initial post-treatment follow-up over 48 weeks
- Long-term follow-up for 4 additional years
This trial will be conducted in accordance with the International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki. Participants must be consented using the approved Informed Consent Form before any procedures specified in the protocol are performed.
- Conditions
- Crigler-Najjar Syndrome
- Being tested
- Imlifidase, GNT0003
- 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.
ImlifidaseDrug
Imlifidase: single administration (dose is confidential), Lyophilized powder for concentrate for solution for infusion
GNT0003Drug
GNT0003: single administration 5E+12 VG/kg, Sterile concentrate for solution for infusion
| Study group | Role | What they receive |
|---|---|---|
| Treatment with imlifidase | Experimental | Each participant will be treated with imlifidase Receives: Drug: Imlifidase |
| Treatment with GNT0003 | Experimental | Each participant will be treated with GNT0003 Receives: Drug: GNT0003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with serum total bilirubin ≤ 300 μmol/L, 48 weeks after GNT0003 infusion and without phototherapy from Week 16
Decrease of serum total bilirubin level after interruption of daily phototherapy; change in serum total bilirubin from baseline to week 48.
Measured: 48 weeks post GNT0003 administration
Secondary outcomes (2)
Incidence of significant clinical and/or laboratoy abnormalities, of all treatment-emergent adverse events, serious adverse events, adverse events of special interrests, adverse drug reactions, malignancies
Incidence and severity for each body system and laboratory parameter will be presented and summarized overall
Measured: 48 weeks; 60 months
Change in Health-related quality of Life form baseline to week 48 post GNT0003 administration
Scale 36-Item Short From Survey (SF-36 Health Survey); from 0 (negative) to 100 (positive)
Measured: 48 weks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2024
- Study start8 Nov 2024
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genethon
- Sponsor type
- University, hospital or other
- Collaborators
- Hansa Biopharma AB
- Responsible party
- Sponsor
- Investigators
- Philippe LABRUNE, MD, PHD, Principal investigator, APHP_Hopital Antoine BECLERE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06518005
- Sponsor's protocol ID
- GNT-018-IDES
- Status last verified
- Jul 2024
- First submitted
- 18 Jul 2024
- Last updated
- 3 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase 2 Trial to Evaluate the Efficacy and Safety of a Single Intravenous Administration of GNT0003 (an Adeno-associated Viral (AAV) Vector Expressing the UGT1A1 Transgene) Following Imlifidase Pre-treatment in Adult Participants With Severe Crigler-Najjar Syndrome (CNS) Requiring Daily Phototherapy and Presenting Pre-existing Anti-AAV8 Antibodies
- ClinicalTrials.gov ID
- NCT06518005
- Acronym / sponsor ID
- GNT-018-IDES
- Conditions
- Crigler-Najjar Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 3 participants (estimated)
- Lead sponsor
- GenethonUniversity, hospital or other
- Collaborators
- Hansa Biopharma AB
- Study start
- 8 Nov 2024 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 24 Jul 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.
Clinical trial rationale:
CNS is an ultra-rare (<1/1 million newborns), autosomal recessive disorder of bilirubin conjugation caused by mutation in the gene coding for uridine 5'-diphosphate glucuronosyltransferase (UGT1A1), that causes the accumulation of neurotoxic unconjugated bilirubin (UCB).
Reduction of UCB is managed with phenobarbital in mild CNS, and daily phototherapy in severe CNS.
There is no authorized curative medical treatment for CNS. Liver transplantation is currently the only curative treatment for severe CNS.
GNT0003 is a genetically modified recombinant (r) viral vector composed of the AAV8 viral capsid carrying the UGT1A1 transgene which aims to correct the dysfunction of the mutated gene by achieving durable expression of a functional copy of the affected gene.
Imlifidase (IgG-degrading enzyme) has demonstrated its efficacy in highly sensitized adult kidney transplant patients.
To give participants with pre-existing anti-AAV8 antibodies access to gene therapy treatments, this trial aims to demonstrate the safety and efficacy of GNT0003 following imlifidase pre-treatment in adult participants with severe CNS requiring daily phototherapy and presenting with pre-existing anti-AAV8 antibodies.
Primary objective: to assess efficacy of a single intravenous administration of GNT0003 following imlifidase pre-treatment in participants with severe CNS requiring phototherapy and pre-existing AAV8 antibodies
Secondary objective: to collect data on safety and tolerability of GNT0003 and imlifidase, efficacy of imlifidase, pharmacokinetic and pharmacodynamic profile of GNT0003, and Quality of Life.
The trial will include 3 parts:
- A baseline period for at least 3 months
- A treatment period
- A follow-up period:
- Initial post-treatment follow-up over 48 weeks
- Long-term follow-up for 4 additional years
This trial will be conducted in accordance with the International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki. Participants must be consented using the approved Informed Consent Form before any procedures specified in the protocol are performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment with imlifidase | Experimental | Drug: ImlifidaseEach participant will be treated with imlifidase |
| Treatment with GNT0003 | Experimental | Drug: GNT0003Each participant will be treated with GNT0003 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (9 listed)
- Participation in another interventional trial within 6 months prior to start of clinical trial intervention and during the whole clinical trial
- Fibrosis score ≥ 3 (METAVIR) or 10 kPa (FibroScan®)
- Liver transplantation
- Significant underlying liver disease, chronic hepatitis B, C and/or infected with Human immunodeficiency virus
- Any other clinically significant illness
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 |
|---|---|---|
| ImlifidaseImlifidase: single administration (dose is confidential), Lyophilized powder for concentrate for solution for infusion | Drug | Treatment with imlifidase |
| GNT0003GNT0003: single administration 5E+12 VG/kg, Sterile concentrate for solution for infusion | Drug | Treatment with GNT0003 |
Primary outcome
Proportion of participants with serum total bilirubin ≤ 300 μmol/L, 48 weeks after GNT0003 infusion and without phototherapy from Week 16
Time frame: 48 weeks post GNT0003 administration
Decrease of serum total bilirubin level after interruption of daily phototherapy; change in serum total bilirubin from baseline to week 48.
2 secondary outcomes
Incidence of significant clinical and/or laboratoy abnormalities, of all treatment-emergent adverse events, serious adverse events, adverse events of special interrests, adverse drug reactions, malignancies
Time frame: 48 weeks; 60 months
Change in Health-related quality of Life form baseline to week 48 post GNT0003 administration
Time frame: 48 weks
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 3 Dec 2024.
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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.
GENETHON Clinical Development Department contact
Philippe LABRUNE, MD, PHD principal investigator
APHP_Hopital Antoine BECLERE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imlifidase and GNT0003 in people with Crigler-Najjar Syndrome, run by Genethon at 1 site in France.
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 0 inclusion and 9 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 3 Dec 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 France. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 GENETHON Clinical Development Department (+33 (0) 1 69 47 10 32, clinicaldevelopment@genethon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with serum total bilirubin ≤ 300 μmol/L, 48 weeks after GNT0003 infusion and without phototherapy from Week 16 (time frame: 48 weeks post GNT0003 administration). 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 3 Dec 2024.