Usher SyndromePhase 1/2NCT01505062
Study of SAR421869 in Participants With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B
A Phase 1/2 study testing SAR421869 in people with Usher Syndrome and Retinitis Pigmentosa, run by Sanofi at 2 sites in 2 countries.
Trial summary
To evaluate the safety and tolerability of ascending doses of subretinal injections of SAR421869 in participants with Usher syndrome type 1B. To evaluate for possible biological activity of SAR421869. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Usher Syndrome, Retinitis Pigmentosa
- What is being tested?
- SAR421869
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 26 Mar 2012to 16 Aug 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinical and molecular diagnosis of Retinitis Pigmentosa associated with Usher Syndrome type 1B, caused by at least one pathogenic myosin 7a gene (MYO7A) mutation on both alleles, confirmed by direct sequencing and co-segregation analysis within the participant's family.
- Suitable verbal/auditory and/or tactile sign language communication (in the opinion of the investigator) as to allow written informed consent to be obtained.
- Women of childbearing potential had a negative pregnancy test at screening and at baseline, and agree to use an effective form of contraception such as the contraceptive pill or intra uterine device for at least three months following SAR421869 administration, or be surgically sterile or postmenopausal, with the last menstrual period being over two years prior to enrolment.
- Males of reproductive potential agreed with their partner to use two forms of contraception, including one barrier method for at least three months following SAR421869 administration if their partner was of childbearing capacity, or must be surgically sterile.
- Participants agreed to not donate blood, organs, tissues or cells for at least three months following SAR421869 administration.
Who cannot join
- Presence of significant ocular abnormalities in the study eye that in the opinion of the investigator would preclude the planned surgery, effective safety follow-up, or interfere with the interpretation of study outcome measures (e.g., glaucoma, corneal or significant lens opacities, pre-existing uveitis, intraocular infection, choroidal neovascularization).
- Any pre-existing factor or past history of eye disease in children that might predispose to an increased risk of surgical complications in the study eye (e.g., trauma, previous surgery, uveitis, congenital, developmental or structural abnormalities).
- Concomitant systemic diseases including those in which the disease itself, or the treatment for the disease, can alter ocular function (e.g., malignancies, diabetes, juvenile rheumatoid arthritis or sickle cell disease).
- Any contraindication to pupil dilation in either eye.
- Contraindications to use of anesthesia (local or general, as appropriate).
- Treatment with intravitreal, subtenon, or periocular steroid within 4 months of the screening visit.
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- Any known allergy to any component of the delivery vehicle or diagnostic agents used during the study (e.g., fluorescein, dilation drops), or medications planned for use during the peri-operative period, particularly topical, injected or systemic corticosteroids.
- Life-threatening illness.
- Alcohol or other substance abuse.
- History of malignancy within a five year period or have had a positive cancer screening test within a one year period of the screening visit.
- Laboratory test abnormalities or abnormalities in electrocardiogram or chest X-ray, that in the opinion of the principal investigator, are clinically significant and would make the participant unsuitable for participation in the study.
- Intercurrent illness or infection 28 days prior to SAR421869 administration.
- Concurrent anti-retroviral therapy that would inactivate the investigational agent.
- Current treatment with immunosuppressant therapies.
- Pre-menopausal or non-surgically sterile women who were unwilling to use an effective form of contraception such as the contraceptive pill or intrauterine device.
- Men or women who did not agree to use barrier contraception as specified in the inclusion criteria.
- Pregnant or breastfeeding women.
- History of any investigational agent within 28 days prior to SAR421869 administration.
- Participation in a prior gene transfer therapy study.
- Enrolment in any other clinical study, for any condition, including those relating to Usher syndrome Type 1B, throughout the duration of the SAR421869 study.
- Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery.
- Past medical history of HIV, or hepatitis A, B or C.
- Inability to comply with the study protocol.
- Any ocular surgery including laser and cataract surgery with intraocular lens implantation, aphakia or prior vitrectomy, in the study eye within 6 months of screening.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Investigational Site Number 840001
Portland, Oregon, 97239-3098
About this study
Official title: A Phase I/IIA Dose Escalation Safety Study of Subretinally Injected SAR421869, Administered to Patients With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B
To evaluate the safety and tolerability of ascending doses of subretinal injections of SAR421869 in participants with Usher syndrome type 1B.
To evaluate for possible biological activity of SAR421869.
Read the detailed description
Following screening procedures, the gene transfer agent were injected once only under the retina by an opthalmic surgeon under anesthesia. Participants then had regular follow-up visits where general health examinations, blood tests and ophthalmic examinations including best corrected visual acuity, slit lamp examination, intraocular pressure, fundoscopy, autofluorescence, optical coherence tomography, perimetry and electroretinogram were undertaken.
At the end of the study, the participants were invited to enter in an open-label safety study for long-term follow-up visits (at least once every six months) including ophthalmological examinations and recording of adverse events (AEs) were continued for 5 years; then the Investigator followed the participants by telephone for a subsequent 10 years at a minimum interval of once a year to monitor delayed AEs.
- Conditions
- Usher Syndrome, Retinitis Pigmentosa
- Being tested
- SAR421869
- Keywords
- Usher Syndrome Retinitis Pigmentosa, Usher Syndrome associated Retinitis Pigmentosa
- Medical subject headings
- Usher Syndromes, Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAR421869Drug
Also called UshStat®
Formulation: Sterile suspension for intraocular injection, 100 microliters (μL) aliquots in 0.3 milliliter (mL) type I borosilicate glass 'V' vials with a butyl stopper and aluminum crimp seal.
Route of administration: subretinal injection
| Study group | Role | What they receive |
|---|---|---|
| SAR421869 (Cohort 1) | Experimental | Starting dose of SAR421869 given through one subretinal injection. Receives: Drug: SAR421869 |
| SAR421869 (Cohort 2) | Experimental | Escalating dose of SAR421869 given through one subretinal injection. Receives: Drug: SAR421869 |
| SAR421869 (Cohort 3) | Experimental | Escalating dose of SAR421869 given through one subretinal injection. Receives: Drug: SAR421869 |
| SAR421869 (Cohort 4) | Experimental | Maximum tolerated dose (MTD) of SAR421869 given through one subretinal injection. Receives: Drug: SAR421869 |
| SAR421869 (Cohort 5) | Experimental | MTD of SAR421869 given through one subretinal injection. Receives: Drug: SAR421869 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any unfavorable and unintended physical sign, symptom, or laboratory parameter that developed or worsened in severity during the course of the study, whether or not considered related to the IMP. The TEAEs were defined as any event that started or increased in severity after the participant received IMP, including abnormal laboratory results, electrocardiogram, etc.
Measured: From Baseline to Week 48
Percentage of Participants With TEAEs by Severity
An AE was any unfavorable and unintended physical sign, symptom, or laboratory parameter that developed or worsened in severity during the course of the study, whether or not considered related to the IMP. The TEAEs were defined as any event that started or increased in severity after the participant received IMP, including abnormal laboratory results, electrocardiogram, etc. For each AE, the severity was categorized as either mild, moderate or severe where 'mild' was defined as discomfort noticed but did not interfere with the participant's daily routines (an annoyance), 'moderate' was defined as some impairment of function, not hazardous to health (uncomfortable or embarrassing), and 'severe' was defined as significant impairment of function, hazardous to health (incapacitating).
Measured: From Baseline to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2012 (estimated)
- Study start26 Mar 2012
- Primary completion16 Aug 2019
- Study completion16 Aug 2019
Why it stopped: Study stopped not for safety reasons. Due to review of clinical development plans and priorities, Sponsor decided to stop development of the product.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Usher SyndromeStudies of the same condition, open and under way.
- More trials run by SanofiThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard Weleber, MD, Principal investigator, Casey Eye Institute, Portland, OregonJose-Alain Sahel, MD, PhD, Principal investigator, Hopital Nationale des Quinze-Vingt, Paris France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01505062
- Sponsor's protocol ID
- TDU13600
- Other IDs
- US1/001/10
- Status last verified
- Mar 2022
- First submitted
- 4 Jan 2012
- Last updated
- 28 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Publications
Zallocchi M, Binley K, Lad Y, Ellis S, Widdowson P, Iqball S, Scripps V, Kelleher M, Loader J, Miskin J, Peng YW, Wang WM, Cheung L, Delimont D, Mitrophanous KA, Cosgrove D. EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat. PLoS One. 2014 Apr 4;9(4):e94272. doi: 10.1371/journal.pone.0094272. eCollection 2014.
PubMed 24705452
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIA Dose Escalation Safety Study of Subretinally Injected SAR421869, Administered to Patients With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B
- ClinicalTrials.gov ID
- NCT01505062
- Acronym / sponsor ID
- TDU13600
- Conditions
- Usher Syndrome, Retinitis Pigmentosa
- Keywords
- Usher Syndrome Retinitis Pigmentosa, Usher Syndrome associated Retinitis Pigmentosa
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped not for safety reasons. Due to review of clinical development plans and priorities, Sponsor decided to stop development of the product.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 26 Mar 2012 (actual)
- Primary completion
- 16 Aug 2019 (actual)
- Study completion
- 16 Aug 2019 (actual)
- First posted
- 6 Jan 2012 (estimated)
- Results
- Posted 18 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and tolerability of ascending doses of subretinal injections of SAR421869 in participants with Usher syndrome type 1B.
To evaluate for possible biological activity of SAR421869.
Detailed description
Following screening procedures, the gene transfer agent were injected once only under the retina by an opthalmic surgeon under anesthesia. Participants then had regular follow-up visits where general health examinations, blood tests and ophthalmic examinations including best corrected visual acuity, slit lamp examination, intraocular pressure, fundoscopy, autofluorescence, optical coherence tomography, perimetry and electroretinogram were undertaken.
At the end of the study, the participants were invited to enter in an open-label safety study for long-term follow-up visits (at least once every six months) including ophthalmological examinations and recording of adverse events (AEs) were continued for 5 years; then the Investigator followed the participants by telephone for a subsequent 10 years at a minimum interval of once a year to monitor delayed AEs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| SAR421869 (Cohort 1) | Experimental | Drug: SAR421869Starting dose of SAR421869 given through one subretinal injection. |
| SAR421869 (Cohort 2) | Experimental | Drug: SAR421869Escalating dose of SAR421869 given through one subretinal injection. |
| SAR421869 (Cohort 3) | Experimental | Drug: SAR421869Escalating dose of SAR421869 given through one subretinal injection. |
| SAR421869 (Cohort 4) | Experimental | Drug: SAR421869Maximum tolerated dose (MTD) of SAR421869 given through one subretinal injection. |
| SAR421869 (Cohort 5) | Experimental | Drug: SAR421869MTD of SAR421869 given through one subretinal injection. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Clinical and molecular diagnosis of Retinitis Pigmentosa associated with Usher Syndrome type 1B, caused by at least one pathogenic myosin 7a gene (MYO7A) mutation on both alleles, confirmed by direct sequencing and co-segregation analysis within the participant's family.
- Suitable verbal/auditory and/or tactile sign language communication (in the opinion of the investigator) as to allow written informed consent to be obtained.
- Women of childbearing potential had a negative pregnancy test at screening and at baseline, and agree to use an effective form of contraception such as the contraceptive pill or intra uterine device for at least three months following SAR421869 administration, or be surgically sterile or postmenopausal, with the last menstrual period being over two years prior to enrolment.
- Males of reproductive potential agreed with their partner to use two forms of contraception, including one barrier method for at least three months following SAR421869 administration if their partner was of childbearing capacity, or must be surgically sterile.
- Participants agreed to not donate blood, organs, tissues or cells for at least three months following SAR421869 administration.
Key exclusion criteria (24 listed)
- Presence of significant ocular abnormalities in the study eye that in the opinion of the investigator would preclude the planned surgery, effective safety follow-up, or interfere with the interpretation of study outcome measures (e.g., glaucoma, corneal or significant lens opacities, pre-existing uveitis, intraocular infection, choroidal neovascularization).
- Any pre-existing factor or past history of eye disease in children that might predispose to an increased risk of surgical complications in the study eye (e.g., trauma, previous surgery, uveitis, congenital, developmental or structural abnormalities).
- Concomitant systemic diseases including those in which the disease itself, or the treatment for the disease, can alter ocular function (e.g., malignancies, diabetes, juvenile rheumatoid arthritis or sickle cell disease).
- Any contraindication to pupil dilation in either eye.
- Contraindications to use of anesthesia (local or general, as appropriate).
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 |
|---|---|---|
| SAR421869Also: UshStat®Formulation: Sterile suspension for intraocular injection, 100 microliters (μL) aliquots in 0.3 milliliter (mL) type I borosilicate glass 'V' vials with a butyl stopper and aluminum crimp seal. Route of administration: subretinal injection | Drug | SAR421869 (Cohort 1), SAR421869 (Cohort 2), SAR421869 (Cohort 3), SAR421869 (Cohort 4), SAR421869 (Cohort 5) |
Primary outcome
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From Baseline to Week 48
An adverse event (AE) was any unfavorable and unintended physical sign, symptom, or laboratory parameter that developed or worsened in severity during the course of the study, whether or not considered related to the IMP. The TEAEs were defined as any event that started or increased in severity after the participant received IMP, including abnormal laboratory results, electrocardiogram, etc.
Percentage of Participants With TEAEs by Severity
Time frame: From Baseline to Week 48
An AE was any unfavorable and unintended physical sign, symptom, or laboratory parameter that developed or worsened in severity during the course of the study, whether or not considered related to the IMP. The TEAEs were defined as any event that started or increased in severity after the participant received IMP, including abnormal laboratory results, electrocardiogram, etc. For each AE, the severity was categorized as either mild, moderate or severe where 'mild' was defined as discomfort noticed but did not interfere with the participant's daily routines (an annoyance), 'moderate' was defined as some impairment of function, not hazardous to health (uncomfortable or embarrassing), and 'severe' was defined as significant impairment of function, hazardous to health (incapacitating).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24705452Zallocchi M, Binley K, Lad Y, Ellis S, Widdowson P, Iqball S, Scripps V, Kelleher M, Loader J, Miskin J, Peng YW, Wang WM, Cheung L, Delimont D, Mitrophanous KA, Cosgrove D. EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat. PLoS One. 2014 Apr 4;9(4):e94272. doi: 10.1371/journal.pone.0094272. eCollection 2014.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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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.
Richard Weleber, MD principal investigator
Casey Eye Institute, Portland, Oregon
Jose-Alain Sahel, MD, PhD principal investigator
Hopital Nationale des Quinze-Vingt, Paris France
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SAR421869 in people with Usher Syndrome and Retinitis Pigmentosa, run by Sanofi at 2 sites in 2 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 5 inclusion and 24 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 28 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 18 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From Baseline to Week 48). 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 NCT01505062, 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 Apr 2022.