Stargardt's DiseasePhase 1/2NCT01367444
Phase I/IIA Study of SAR422459 in Participants With Stargardt's Macular Degeneration
A Phase 1/2 study testing SAR422459 in people with Stargardt's Disease, run by Sanofi at 5 sites in 2 countries.
Trial summary
Primary Objective: To assess the safety and tolerability of ascending doses of SAR422459 in participants with Stargardt's Macular Degeneration (SMD). Secondary Objective: To evaluate for possible biological activity of SAR422459. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Stargardt's Disease
- What is being tested?
- SAR422459
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 8 Jun 2011to 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
- Signed and dated written informed consent obtained from the participant and/or the participant's legally acceptable representative.
- Diagnosis of SMD, with at least one pathogenic mutant ABCA4 allele on each chromosome.
- Women of childbearing potential must had a negative pregnancy test at Day -1, and agree to use an effective form of contraception for at least three months, or be surgically sterile or postmenopausal, with the last menstrual period being over two years prior to enrollment.
- Males must agree with their partner to use two forms of contraception for at least three months following SAR422459 administration.
- Participants must agree to not donate blood, organs, tissues or cells for at least three months following SAR422459 administration.
- Participants enrolled in France must be affiliated to or benefit from a social security regimen.
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- Specific Inclusion Criteria Participant Group A:
- Participants (18 years or older) with advanced SMD.
- Visual acuity less than or equal to (<=) 20/200 in the worst eye.
- Severe cone-rod dysfunction with no detectable or severely abnormal full-field electroretinogram responses.
- Specific Inclusion Criteria Participant Group B:
- Participants (18 years or older) with SMD.
- Visual Acuity <=20/200 in the worst eye.
- Abnormal full-field electroretinogram responses.
- Specific Inclusion Criteria Participant Group C:
- Participants (18 years or older) with SMD.
- Visual acuity <=20/100 in the worst eye.
- Abnormal full-field electroretinogram responses.
- Specific Inclusion Criteria Participant Group D:
- Symptomatic participants (from 6 years to 26 years old) with early or childhood-onset SMD (age at disease onset [less than] <18 years) with at least one pathogenic mutant ABCA4 allele on each chromosome confirmed by direct sequencing and co-segregation analysis within the participant's family.
- Visual acuity of greater than or equal to (>=) 20/200 in both eyes at the time of the screening visit.
- Participants were anticipated to experience rapid deterioration in visual function and/or retinal structure as determined by an annual progression rate in at least one of the following parameters occurring in at least one eye (assessments recorded up to 2 years prior to the screening visit date might be considered to document evidence of rapid deterioration):
- Loss of >=1 line of Snellen visual acuity (equivalent to 5 early treatment diabetic retinopathy study [ETDRS] letters).
- Reduction in macular mean sensitivity of >=1.2 decibels (dB) as assessed by microperimetry.
- Reduction in macular mean sensitivity of >=5 dB or reduction in hill of vision by greater than (>)14 dB-sr as assessed by static perimetry.
- Enlargement in the area of macular retinal pigment epithelial (RPE) atrophy by fundus autofluorescence at a rate of >=0.5 millimeter square(mm^2).
- Enlargement in the area of central macular retinal thinning/photoreceptor loss by ocular coherence tomography at a rate of >=0.5 mm^2.
- All eligible participants must demonstrate an ability to understand, willingness to cooperate and ability to reliably perform required study procedures as judged and confirmed by the study investigator.
- Specific inclusion criteria Participant Group E:
- Symptomatic participants (between 6 years and 17 years old) with early or childhood-onset SMD with at least one pathogenic mutant ABCA4 allele on each chromosome confirmed by direct sequencing and co-segregation analysis within the participant's family.
- Visual acuity of >=20/100 in both eyes at the time of screening visit.
- Participants were anticipated to experience rapid deterioration in visual function and/or retinal structure as determined by an annual progression rate in at least one of the following parameters occurring in at least one eye (assessments recorded up to 2 years prior to the screening visit date were considered to document evidence of rapid deterioration):
- Loss of >=1 line of Snellen visual acuity (equivalent to 5 ETDRS letters).
- Reduction in macular mean sensitivity of >=1.2 dB as assessed by microperimetry.
- Reduction in macular mean sensitivity of >=5 dB or reduction in hill of vision by >14 dB-sr as assessed by static perimetry.
- Enlargement in the area of macular RPE atrophy by fundus autofluorescence at a rate of >=0.5 mm^2.
- Enlargement in the area of central macular retinal thinning/photoreceptor loss by ocular coherence tomography at a rate of >=0.5 mm^2.
- All eligible participants demonstrated an ability to understand, willingness to cooperate and ability to reliably perform required study procedures as judged and confirmed by the study investigator.
Who cannot join
- Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study outcome measures.
- Cataract surgery with intraocular lens implantation within 6 months of enrolment.
- Aphakia or prior vitrectomy in the study eye.
- Concomitant systemic diseases including those in which the disease itself, or the treatment for the disease, can alter ocular function.
- Any intraocular surgery or laser in either eye planned within 6 months of Day 0.
- Any contraindication to pupil dilation in either eye.
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- Any known allergy to any component of the delivery vehicle or diagnostic agents used during the study, or medications planned for use in the perioperative period particularly topical, injected or systemic corticosteroids.
- Any injectable intravitreal treatment to the treated eye or intravitreal device in the treated eye within 6 months prior to screening.
- Any periocular injections of corticosteroids to the treated eye within 4 months prior to screening.
- Laboratory test abnormalities or abnormalities in electrocardiogram, chest X-rays that in the opinion of the Principal Investigator would make the participant unsuitable for participation in the study.
- Significant intercurrent illness or infection during the 28 days prior to enrolment.
- 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.
- Alcohol or other substance abuse.
- Contraindications to use of anesthesia (local or general, as appropriate).
- Concurrent anti-retroviral therapy that would inactivate the investigational agent.
- History of any investigational agent within 28 days prior to SAR422459 administration.
- Participation in a prior ocular gene transfer therapy study.
- Enrolment in any other clinical treatment study throughout the duration of the SAR422459 study.
- Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery.
- A past medical history of human immunodeficiency virus or hepatitis A, B, or C infection.
- Women who were pregnant or were breastfeeding.
- History or signs consistent with unilateral amblyopia (strabismic, anisometropic, or stimulus deprivation).
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Investigational Site Number 840004
Houston, Texas, 77030
Investigational Site Number 840005
Iowa City, Iowa, 52242
Investigational Site Number 840002
Miami, Florida, 33136
Investigational Site Number 840001
Portland, Oregon, 97239-3098
About this study
Official title: A Phase I/IIA Dose Escalation Safety Study of Subretinally Injected SAR422459, Administered to Patients With Stargardt's Macular Degeneration
Primary Objective:
To assess the safety and tolerability of ascending doses of SAR422459 in participants with Stargardt's Macular Degeneration (SMD).
Secondary Objective:
To evaluate for possible biological activity of SAR422459.
Read the detailed description
The total duration per participant was up to 52 weeks, which included 4 week screening period and 48 weeks study period.
At the end of the study, the participants were invited to enter in an open-label safety study (LTS13588-NCT01736592) for long-term follow-up visits including ophthalmological examinations and recording of adverse events (AEs) for up to 15 years.
- Conditions
- Stargardt's Disease
- Being tested
- SAR422459
- Keywords
- Stargardt's Disease
- Medical subject headings
- Stargardt Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAR422459Drug
Pharmaceutical form: sterile solution, 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 |
|---|---|---|
| SAR422459 (Dose 1) | Experimental | Starting dose of SAR422459 given through subretinal injection Receives: Drug: SAR422459 |
| SAR422459 (Dose 2) | Experimental | Escalating dose of SAR422459 given through subretinal injection Receives: Drug: SAR422459 |
| SAR422459 (Dose 3) | Experimental | Maximum tolerated dose (MTD) of SAR422459 given through subretinal injection Receives: Drug: SAR422459 |
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 investigational product. The TEAEs were defined as any event that started or increased in severity after the participant received investigational medicinal product (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 investigational product. 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 posted7 Jun 2011 (estimated)
- Study start8 Jun 2011
- 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 (2)Papers the sponsor has linked to this study.
- Other trials for Stargardt's DiseaseStudies 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Yang, MD, Principal investigator, Oregon Health & Science University, Portland, OregonJose-Alain Sahel, MD. Ph.D, Principal investigator, Hopital Nationale des Quinze-Vingt, Paris France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01367444
- Sponsor's protocol ID
- TDU13583
- Other IDs
- SG1/001/10
- Status last verified
- Mar 2022
- First submitted
- 3 Jun 2011
- Last updated
- 14 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- 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
Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.
PubMed 30194931Parker MA, Choi D, Erker LR, Pennesi ME, Yang P, Chegarnov EN, Steinkamp PN, Schlechter CL, Dhaenens CM, Mohand-Said S, Audo I, Sahel J, Weleber RG, Wilson DJ. Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial. Transl Vis Sci Technol. 2016 Oct 1;5(5):10. doi: 10.1167/tvst.5.5.10. eCollection 2016 Oct.
PubMed 27730010
Study at a glance
From the registry record, last updated by the sponsor on 14 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 SAR422459, Administered to Patients With Stargardt's Macular Degeneration
- ClinicalTrials.gov ID
- NCT01367444
- Acronym / sponsor ID
- TDU13583
- Conditions
- Stargardt's Disease
- Keywords
- Stargardt's Disease
- 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
- 27 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2011 (actual)
- Primary completion
- 16 Aug 2019 (actual)
- Study completion
- 16 Aug 2019 (actual)
- First posted
- 7 Jun 2011 (estimated)
- Results
- Posted 5 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To assess the safety and tolerability of ascending doses of SAR422459 in participants with Stargardt's Macular Degeneration (SMD).
Secondary Objective:
To evaluate for possible biological activity of SAR422459.
Detailed description
The total duration per participant was up to 52 weeks, which included 4 week screening period and 48 weeks study period.
At the end of the study, the participants were invited to enter in an open-label safety study (LTS13588-NCT01736592) for long-term follow-up visits including ophthalmological examinations and recording of adverse events (AEs) for up to 15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SAR422459 (Dose 1) | Experimental | Drug: SAR422459Starting dose of SAR422459 given through subretinal injection |
| SAR422459 (Dose 2) | Experimental | Drug: SAR422459Escalating dose of SAR422459 given through subretinal injection |
| SAR422459 (Dose 3) | Experimental | Drug: SAR422459Maximum tolerated dose (MTD) of SAR422459 given through 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 (38 listed)
- Signed and dated written informed consent obtained from the participant and/or the participant's legally acceptable representative.
- Diagnosis of SMD, with at least one pathogenic mutant ABCA4 allele on each chromosome.
- Women of childbearing potential must had a negative pregnancy test at Day -1, and agree to use an effective form of contraception for at least three months, or be surgically sterile or postmenopausal, with the last menstrual period being over two years prior to enrollment.
- Males must agree with their partner to use two forms of contraception for at least three months following SAR422459 administration.
- Participants must agree to not donate blood, organs, tissues or cells for at least three months following SAR422459 administration.
Key exclusion criteria (22 listed)
- Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study outcome measures.
- Cataract surgery with intraocular lens implantation within 6 months of enrolment.
- Aphakia or prior vitrectomy in the study eye.
- Concomitant systemic diseases including those in which the disease itself, or the treatment for the disease, can alter ocular function.
- Any intraocular surgery or laser in either eye planned within 6 months of Day 0.
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 |
|---|---|---|
| SAR422459Pharmaceutical form: sterile solution, 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 | SAR422459 (Dose 1), SAR422459 (Dose 2), SAR422459 (Dose 3) |
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 investigational product. The TEAEs were defined as any event that started or increased in severity after the participant received investigational medicinal product (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 investigational product. 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 14 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30194931Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.
- Derived from this study: PubMed 27730010Parker MA, Choi D, Erker LR, Pennesi ME, Yang P, Chegarnov EN, Steinkamp PN, Schlechter CL, Dhaenens CM, Mohand-Said S, Audo I, Sahel J, Weleber RG, Wilson DJ. Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial. Transl Vis Sci Technol. 2016 Oct 1;5(5):10. doi: 10.1167/tvst.5.5.10. eCollection 2016 Oct.
- 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.
Paul Yang, MD principal investigator
Oregon Health & Science University, Portland, Oregon
Jose-Alain Sahel, MD. Ph.D principal investigator
Hopital Nationale des Quinze-Vingt, Paris France
5 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 SAR422459 in people with Stargardt's Disease, run by Sanofi at 5 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 38 inclusion and 22 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 14 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 5 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 5 Jun 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 NCT01367444, which also lists 2 linked publications.
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 14 Apr 2022.