Cystic FibrosisONB-CFTRNCT05100823
Validation of Therapeutic Efficacy Targeting the Splicing Variants in Cystic Fibrosis and CFTR Pathologies
A study testing Nasal cells sampling and Rectal biopsy sampling in people with Cystic Fibrosis and CFTR Gene Mutation, run by University Hospital, Montpellier at 1 site in France.
Trial summary
Cystic Fibrosis, an inherited autosomal recessive disease, arises from mutations in the CFTR gene. For intronic mutations affecting splicing events, oligonucleotides therapy has the potential to restore the production of the full length CFTR protein. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis, CFTR Gene Mutation
- What is being tested?
- Nasal cells sampling and Rectal biopsy sampling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteFrance
- Study dates
- 30 Mar 2022to 17 Feb 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The subject must have given their free and informed consent and signed the consent
- The subject must be affiliated or beneficiary of a health insurance plan Women and men are included
- The patient is at least 12 years old.
- The patient has cystic fibrosis or a CFTR pathology and therefore carries two mutations (with at least one mutation affecting splicing) in the CFTR gene.
- Patients who volunteer for rectal biopsy collection (only from Montpellier University Hospital) must be at least 18 years old.
Who cannot join
- The subject is in a period of exclusion determined by a previous study.
- The subject is under judicial protection, under guardianship or under curatorship
- The subject does not accept to sign consent
- It turns out to be impossible to give informed information to the subject
- The subject does not read the French language fluently
- The subject is a pregnant or breastfeeding woman
Show all 11Show fewer
- The subject has porphyria, or has hepatic insufficiency, or suffers from epilepsy, or suffers from conduction disorders, or suffers from severe heart failure, has a cons-indication to the use of a local anesthetic spray.
- Specific non-inclusion criteria for rectal sampling:
- the subject has thrombocytopenia
- the subject has a bleeding disorder
- The patient has severe inflammation of the rectum.
Trial locations and contacts
1 site in 1 country.
About this study
Cystic Fibrosis, an inherited autosomal recessive disease, arises from mutations in the CFTR gene. For intronic mutations affecting splicing events, oligonucleotides therapy has the potential to restore the production of the full length CFTR protein. Recent scientific research has demonstrated the potential of this approach to restore full length mRNA CFTR in in vitro human airway cells. The study aims to validate the therapeutic efficacy of oligonucleotide blockers (ONB) that target splicing defects associated to splicing variants in epithelia obtained from patients with Cystic Fibrosis and CFTR-related disorders.
Read the detailed description
The study will include patients with various CFTR genotypes. The assessment of ONB (named ONB-CFTR) will be performed using an air-liquid interface model of airway epithelium, developed from nasal cells of patients, without or with a combination of existing CFTR modulators, depending on the patient' genotype.
This study will also aim to build a local biobank of rectal organoids from patients (only from Montpellier, France) carrying rare CFTR disease-causing variants.
- Conditions
- Cystic Fibrosis, CFTR Gene Mutation
- Being tested
- Nasal cells sampling, Rectal biopsy sampling
- Keywords
- genetics, cystic fibrosis, personalized therapy, Antisense OligoNucleotide strategy, splicing events, intronic variant
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nasal cells samplingProcedure or surgery
Nasal epithelium brushing in intermediate turbinate using a specific curette following a local anesthesia with Xylocaine 5% nebulizer.
Rectal biopsy samplingProcedure or surgery
Forceps Biopsy Procedure (Servidoni et al., 2013) Only for volunteer patients included in the Montpellier center.
| Study group | Role | What they receive |
|---|---|---|
| Nasal cells sampling and/or rectal biospy | Experimental | Depending of the patient' genotype, specific ONB-CFTR (50 nM) will be incubated at the apical face of in vitro epithelium, alone and in combination with CFTR modulators. Efficacy of ONB will be compared to a condition with oligonucleotide control incubation.
Rectal biopsies from volunteer patients were stored as a bio-bank of organoids. Receives: Procedure: Nasal cells sampling; Procedure: Rectal biopsy sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Restoration of the correctly spliced CFTR mRNA (full length) using specific ONB-CFTR (designed for one splicing variant).
The increase will be assessed in comparison to oligonucleotide-control effect by using semi-quantitative fluorescent PCR.
Measured: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Restoration of the mature CFTR protein using specific ONB-CFTR (designed for one splicing variant).
The increase will be assessed in comparison to oligonucleotide-control effect by using western blot
Measured: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Restoration of CFTR channel function using specific ONB-CFTR (designed for one splicing variant).
The increase will be assessed in comparison to oligonucleotide-control effect by using electrophysiological assays (Ussing chamber).
Measured: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Secondary outcomes (5)
Restoration of the correctly spliced CFTR mRNA (full length) and mature CFTR protein and CFTR channel function using a pool of ONB-CFTR (a mix of specific ONB-CFTR).
The increase will be assessed in comparison to oligonucleotide-control effect by using semi-quantitative fluorescent PCR, western blot and electrophysiological assays (Ussing chamber).
Measured: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Assessment of the amount of CFTR mRNA with normal splicing under the conditions tested.
That parameter will be quantified in comparison to oligonucleotide-control effect by using quantitative PCR assays.
Measured: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Assessment of the amount of mature CFTR proteins under the conditions tested.
That parameter will be quantified in comparison to oligonucleotide-control effect by using western blot assays.
Measured: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Assessment of the CFTR channel activity under the conditions tested.
That parameter will be quantified in comparison to oligonucleotide-control effect by using electrophysiological assays (Ussing chamber).
Measured: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Increase of CFTR channel function using ONB-CFTR and CFTR modulators (correctors and/or potentiators) under the conditions tested.
The increase will be assessed in comparison to oligonucleotide-control effect by using electrophysiological assays (Ussing chamber).
Measured: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2021
- Study start30 Mar 2022
- Primary completion17 Feb 2025
- Study completion17 Feb 2025
Why it stopped: Enrolment period completed and sufficient number of enrolments to achieve study objectives
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe 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
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Collaborators
- Foch Hospital, Suresnes, FRANCE, Hôpital Necker-Enfants Malades, Hôpital Cochin
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05100823
- Sponsor's protocol ID
- RECHMPL20_0423
- Other IDs
- 2020-A03529-30
- Acronym
- ONB-CFTR
- Status last verified
- Sep 2025
- First submitted
- 6 Sep 2021
- Last updated
- 18 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of Therapeutic Efficacy Targeting the Splicing Variants in Cystic Fibrosis and CFTR Pathologies
- ClinicalTrials.gov ID
- NCT05100823
- Acronym / sponsor ID
- ONB-CFTR / RECHMPL20_0423
- Conditions
- Cystic Fibrosis, CFTR Gene Mutation
- Keywords
- genetics, cystic fibrosis, personalized therapy, Antisense OligoNucleotide strategy, splicing events, intronic variant
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrolment period completed and sufficient number of enrolments to achieve study objectives
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Collaborators
- Foch Hospital, Suresnes, FRANCE, Hôpital Necker-Enfants Malades, Hôpital Cochin
- Study start
- 30 Mar 2022 (actual)
- Primary completion
- 17 Feb 2025 (actual)
- Study completion
- 17 Feb 2025 (actual)
- First posted
- 29 Oct 2021 (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.
Cystic Fibrosis, an inherited autosomal recessive disease, arises from mutations in the CFTR gene. For intronic mutations affecting splicing events, oligonucleotides therapy has the potential to restore the production of the full length CFTR protein. Recent scientific research has demonstrated the potential of this approach to restore full length mRNA CFTR in in vitro human airway cells. The study aims to validate the therapeutic efficacy of oligonucleotide blockers (ONB) that target splicing defects associated to splicing variants in epithelia obtained from patients with Cystic Fibrosis and CFTR-related disorders.
Detailed description
The study will include patients with various CFTR genotypes. The assessment of ONB (named ONB-CFTR) will be performed using an air-liquid interface model of airway epithelium, developed from nasal cells of patients, without or with a combination of existing CFTR modulators, depending on the patient' genotype.
This study will also aim to build a local biobank of rectal organoids from patients (only from Montpellier, France) carrying rare CFTR disease-causing variants.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nasal cells sampling and/or rectal biospy | Experimental | Procedure: Nasal cells sampling, Procedure: Rectal biopsy samplingDepending of the patient' genotype, specific ONB-CFTR (50 nM) will be incubated at the apical face of in vitro epithelium, alone and in combination with CFTR modulators. Efficacy of ONB will be compared to a condition with oligonucleotide control incubation. Rectal biopsies from volunteer patients were stored as a bio-bank of organoids. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- The subject must have given their free and informed consent and signed the consent
- The subject must be affiliated or beneficiary of a health insurance plan Women and men are included
- The patient is at least 12 years old.
- The patient has cystic fibrosis or a CFTR pathology and therefore carries two mutations (with at least one mutation affecting splicing) in the CFTR gene.
- Patients who volunteer for rectal biopsy collection (only from Montpellier University Hospital) must be at least 18 years old.
Key exclusion criteria (11 listed)
- The subject is in a period of exclusion determined by a previous study.
- The subject is under judicial protection, under guardianship or under curatorship
- The subject does not accept to sign consent
- It turns out to be impossible to give informed information to the subject
- The subject does not read the French language fluently
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 |
|---|---|---|
| Nasal cells samplingNasal epithelium brushing in intermediate turbinate using a specific curette following a local anesthesia with Xylocaine 5% nebulizer. | Procedure or surgery | Nasal cells sampling and/or rectal biospy |
| Rectal biopsy samplingForceps Biopsy Procedure (Servidoni et al., 2013) Only for volunteer patients included in the Montpellier center. | Procedure or surgery | Nasal cells sampling and/or rectal biospy |
Primary outcome
Restoration of the correctly spliced CFTR mRNA (full length) using specific ONB-CFTR (designed for one splicing variant).
Time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
The increase will be assessed in comparison to oligonucleotide-control effect by using semi-quantitative fluorescent PCR.
Restoration of the mature CFTR protein using specific ONB-CFTR (designed for one splicing variant).
Time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
The increase will be assessed in comparison to oligonucleotide-control effect by using western blot
Restoration of CFTR channel function using specific ONB-CFTR (designed for one splicing variant).
Time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
The increase will be assessed in comparison to oligonucleotide-control effect by using electrophysiological assays (Ussing chamber).
5 secondary outcomes
Restoration of the correctly spliced CFTR mRNA (full length) and mature CFTR protein and CFTR channel function using a pool of ONB-CFTR (a mix of specific ONB-CFTR).
Time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Assessment of the amount of CFTR mRNA with normal splicing under the conditions tested.
Time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Assessment of the amount of mature CFTR proteins under the conditions tested.
Time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Assessment of the CFTR channel activity under the conditions tested.
Time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Increase of CFTR channel function using ONB-CFTR and CFTR modulators (correctors and/or potentiators) under the conditions tested.
Time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
Results and safety
The study was stopped early (reason given: Enrolment period completed and sufficient number of enrolments to achieve study objectives). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2025.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nasal cells sampling and Rectal biopsy sampling in people with Cystic Fibrosis and CFTR Gene Mutation, run by University Hospital, Montpellier 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 5 inclusion and 11 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: stopped early, as of the sponsor's last update on 18 Sep 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 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.
Are results available for this study?
The study was stopped early (reason given: Enrolment period completed and sufficient number of enrolments to achieve study objectives). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Restoration of the correctly spliced CFTR mRNA (full length) using specific ONB-CFTR (designed for one splicing variant). (time frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)). The study lists 3 primary outcomes in all. 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 18 Sep 2025.