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Study of SAR421869 in Patients With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B

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ClinicalTrials.gov Identifier: NCT01505062
Recruitment Status : Recruiting
First Posted : January 6, 2012
Last Update Posted : January 30, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

To evaluate the safety and tolerability of ascending doses of subretinal injections of SAR421869 in patients with Usher syndrome type 1B.

To evaluate for possible biological activity of SAR421869.


Condition or disease Intervention/treatment Phase
Usher Syndrome Retinitis Pigmentosa Genetic: SAR421869 Phase 1 Phase 2

Detailed Description:

Following screening procedures the gene transfer agent will be injected once only under the retina by an opthalmic surgeon under anesthesia. Patients will then have 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 will be undertaken.

At the end of the study, the patient will be invited to enter in an open-label safety study and long-term follow-up visits (at least once every six months) including ophthalmological examinations and recording of adverse events will continue for 5 years; then the Investigator will follow the patient by telephone for a subsequent 10 years at a minimum interval of once a year to monitor delayed adverse events.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 20, 2012
Estimated Primary Completion Date : January 13, 2021
Estimated Study Completion Date : January 13, 2021


Arm Intervention/treatment
Experimental: SAR421869 (Cohort 1)
Starting dose of SAR421869 given through one subretinal injection
Genetic: SAR421869

Pharmaceutical form: prefilled syringes

Route of administration: subretinal injection

Other Name: UshStat

Experimental: SAR421869 (Cohort 2)
Escalating dose of SAR421869 given through one subretinal injection
Genetic: SAR421869

Pharmaceutical form: prefilled syringes

Route of administration: subretinal injection

Other Name: UshStat

Experimental: SAR421869 (Cohort 3)
Escalating dose of SAR421869 given through one subretinal injection
Genetic: SAR421869

Pharmaceutical form: prefilled syringes

Route of administration: subretinal injection

Other Name: UshStat

Experimental: SAR421869 (Cohort 4)
Maximum tolerated dose (MTD) of SAR421869 given through one subretinal injection
Genetic: SAR421869

Pharmaceutical form: prefilled syringes

Route of administration: subretinal injection

Other Name: UshStat

Experimental: SAR421869 (Cohort 5)
MTD of SAR421869 given through one subretinal injection
Genetic: SAR421869

Pharmaceutical form: prefilled syringes

Route of administration: subretinal injection

Other Name: UshStat




Primary Outcome Measures :
  1. The incidence of adverse events [ Time Frame: 48 weeks ]
    The number and percentage of patients with treatment emergent adverse events.


Secondary Outcome Measures :
  1. To determine delay in retinal degeneration following the SAR421869 injection [ Time Frame: 48 weeks ]
    Changes in visual function relative to the untreated contralateral eye utilizing retinal analytical techniques.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical and molecular diagnosis of Retinitis Pigmentosa associated with Usher Syndrome type 1B, caused by at least one pathogenic MYO7A mutation on both alleles, confirmed by direct sequencing and co-segregation analysis within the patient'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 must have 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 must agree with their partner to use two forms of contraception, including one barrier method for at least three months following SAR421869 administration if their partner is of childbearing capacity, or must be surgically sterile.
  • Patients must agree to not donate blood, organs, tissues or cells for at least three months following SAR421869 administration.

Exclusion Criteria:

  • 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 endpoints (eg, 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 may predispose to an increased risk of surgical complications in the study eye (eg, 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 (eg, 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.
  • Any known allergy to any component of the delivery vehicle or diagnostic agents used during the study (eg, 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 patient 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 are unwilling to use an effective form of contraception such as the contraceptive pill or intrauterine device.
  • Men or women who do 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01505062


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com

Locations
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United States, Oregon
Investigational Site Number 840001 Recruiting
Portland, Oregon, United States, 97239-3098
France
Investigational Site Number 250001 Recruiting
Paris, France, 75012
Sponsors and Collaborators
Sanofi
Investigators
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Principal Investigator: Richard Weleber, MD Casey Eye Institute, Portland, Oregon
Principal Investigator: Jose-Alain Sahel, MD, PhD Hopital Nationale des Quinze-Vingt, Paris France

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01505062     History of Changes
Other Study ID Numbers: TDU13600
US1/001/10 ( Other Identifier: Oxford Biomedica )
First Posted: January 6, 2012    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: July 2018

Keywords provided by Sanofi:
Usher Syndrome Retinitis Pigmentosa
Usher Syndrome associated Retinitis Pigmentosa

Additional relevant MeSH terms:
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Syndrome
Retinitis
Retinitis Pigmentosa
Usher Syndromes
Disease
Pathologic Processes
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn
Deaf-Blind Disorders
Deafness
Hearing Loss
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Hearing Loss, Sensorineural
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Blindness
Vision Disorders
Abnormalities, Multiple
Congenital Abnormalities
Signs and Symptoms