RECRUITING

Promising ROd-cone DYstrophy Gene TherapY

Conditions

Retinitis Pigmentosa RHO PDE6A PDE6B Pathogenic Mutation Retinal Disease Eye Disease Rod-Cone Dystrophy Gene Therapy Retinal Dystrophies Retinal Degeneration

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a two-step, multicenter, Phase I/II study including an open-label dose-escalation phase (Step 1) and a three-arm, controlled, double-masked, randomized extension phase (Step 2), in subjects with advanced RCD due to a mutation in the RHO, PDE6A, or PDE6B gene.

Official Title

A Phase I/II Study to Assess the Safety and Tolerability of a Single Subretinal Administration of SPVN06 Gene Therapy in Subjects with Rod-Cone Dystrophy (RCD) Due to a Mutation in the RHO, PDE6A, or PDE6B Gene

Quick Facts

Study Start:2023-04-12

Study Completion:2029-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05748873

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Able to give signed informed consent and comply with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. 2. Age ≥18 years at the time of ICF signature. 3. Subjects of either gender previously diagnosed with advanced RCD due to biallelic mutations in the rod cGMP phosphodiesterase 6 beta (PDE6B) or rod cGMP phosphodiesterase alpha (PDE6A) genes, or due to a monoallelic dominant mutation in the rhodopsin (RHO) gene. The genotyping results must be documented before the initiation of the Screening Visit. Subjects should be retested by the investigator if their genotyping tests were not performed within the 7 previous years, or if they were not performed by an accredited laboratory. In this case, the screening period can be prolonged for 2 additional weeks to allow time to generate genotyping results. 4. Advanced stage is defined as a stage of the natural history of the disease where both distance visual acuity and visual field are affected in both eyes. Substages within the advanced stage are defined as follows (monocular measurements, horizontal axis of isopter III4e for the visual field): * Severe stage is defined by both a BCVA below or equal to 20/200 and above or equal to 20/800, and a visual field below or equal to 20 degrees (subjects of Cohorts 1 to 3) * Intermediate stage is defined by both a BCVA below or equal to 20/40 and above 20/200, and a visual field below or equal to 20 degrees (subjects of Cohorts 4 to 6) 5. For subjects with severe advanced RCD enrolled in Step 1 only, the difference in visual acuity between the two eyes of a given subject should be equal to or below 0.3 logarithm of the minimal angle (LogMAR) (≤3 ETDRS lines), with a tolerance margin of 3 ETDRS letters. 6. Clinical diagnosis of RCD based on past medical and family history, mid-peripheral visual field dysfunction, photopsia, night blindness (nyctalopia), and fundoscopic appearance (including but not restricted to bone spicule pigmentation, attenuation of the retinal vessels, and waxy pallor of the optic nerve). 7. Diagnosis of RCD is confirmed on prior full-field ERG (any previously performed ERG is acceptable). 8. Documented preservation of cone inner and outer segments considered good enough by the investigator for the subject to be included in the study. 9. Negative serum pregnancy test for women of childbearing potential (please refer to Schedule of Assessments for details). 10. Women of childbearing potential (WOCBP) and men and/or their partner(s) of childbearing potential must agree to use a highly effective contraceptive method. This applies to the time period between ICF signature and 12 months after SPVN06 subretinal injection SRI (i.e., no longer applicable to subjects of Cohort 4 after randomization). The definition of highly effective contraceptive methods follows CTFG recommendations. Highly effective contraceptive methods are limited to: * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: * Oral * Intravaginal * Transdermal * Progestogen-only hormonal contraception associated with inhibition of ovulation: * Oral * Injectable * Implantable * Intrauterine device (IUD) * Intrauterine hormone-releasing system (IUS) * Bilateral tubal occlusion * Vasectomized partner * Sexual abstinence 11. Subjects must be affiliated to a health security system, if they are included in a clinical site based in France (per law). 12. No out-of-range values for clinical laboratory tests, however, if outside, must be considered as non-clinically relevant by the investigator using a multidisciplinary approach and compatible with a participation in the clinical study. 13. 12-lead electrocardiogram within normal limits, however, when outside, must be documented by the investigator using a multidisciplinary approach as not clinically relevant and compatible with a participation in the clinical study. Nota bene: This criterion of eligibility is only applicable to subjects assigned to a treatment cohort (Cohorts 1, 2, 3, 5, or 6), and is not required to authorize randomization in Step 2. 14. Physical examination without any clinical findings of clinical relevance (per medical/anesthesia staffs judgment) that could compromise participation in the clinical study or could affect the collection and/or evaluation of the study parameters. The findings of clinical relevance considered as contraindications to SPVN06 treatment include, but are not limited to, pulmonary pathology such as COPD, asthma, cardiac conditions such as congestive heart failure or valve disease, renal issues such as renal insufficiency and endocrine issues such as diabetes.	1. Subjects with prior administration of any gene therapy or any previous treatment with stem cell therapy for ocular or non-ocular disease. 2. Subjects participating in another clinical trial and receiving an investigational medicinal product (IMP) within 5 half-lives or 90 days prior to the injection of SPVN06. 3. Subjects with RCD due to any mutation in genes other than those listed in the inclusion criteria. 4. Subjects with systemic disease or other pathology not related to their diagnosis of RCD, and whose symptoms or associated treatments may affect vision, for example cancers or pathology of the central nervous system. 5. Subjects with narrow irido-corneal angles or any other medical situation contraindicating pupillary dilation. 6. Subjects known to be allergic to any of the delivery vehicle constituents or to any other drugs planned to be used during the clinical study. 7. Subjects with known allergies to corticosteroids, or who will be unable to tolerate the corticosteroid regimen as described in the protocol 8. Subjects with systemic disease or other medical or psychiatric conditions that preclude safe participation in the study. 9. Subjects receiving immunosuppressive therapies, other than the immune modulating regimen described in this protocol, or any other therapy known to influence the immune system including but not limited to steroid implants, cytostatics, interferons, tumor necrosis factor (TNF)-binding proteins, drugs acting on immunophilins, or antibodies with known impact on the immune system. 10. Subjects of reproductive potential unwilling to use effective contraception starting right after ICF signature and for 12 months after SPVN06 SRI (i.e., no longer applicable to subjects of Cohort 4 after randomization). 11. Subjects who are pregnant or breastfeeding. 12. Subjects who are unwilling or unable (based on the investigator's judgment) to comply with the study protocol. 13. Subjects with any condition that would not allow them to complete follow-up examinations during the study and, in the opinion of the investigator, would make them unsuitable for the study. 14. Subjects positive for human immunodeficiency virus (HIV) or any other systemic immunocompromising disease. 15. Subjects who have undergone, within 6 months before inclusion, any significant ocular surgery (per investigator's judgment) that could interfere with the evaluation of SPVN06 study objectives. 16. Presence of eye disorders that could interfere with the assessment of visual acuity and/or any other ocular assessments, including SD-OCT, during the study. 17. Presence of any systemic or ocular diseases, other than non-syndromic retinitis pigmentosa (RP), that can cause vision loss. 18. Prior vitrectomy or vitreomacular surgery. 19. Presence of vitreomacular adhesion or traction, epiretinal membrane macular pucker or macular hole, evident by ophthalmoscopy and/or SD-OCT examinations and assessed by the investigator to significantly affect central vision. 20. Current evidence of retinal detachment assessed by the investigator to significantly affect central vision. 21. Active ocular inflammation or recurrent history of idiopathic or autoimmune-associated uveitis. 22. Subjects with presence of any suspected or active ocular or periocular infection (conjunctivitis, keratitis, scleritis, endophthalmitis). 23. Subjects with history of glaucoma. 24. Subjects with uncontrolled intraocular pressure (IOP). 25. Subjects with active cancer or currently receiving any therapy for cancer treatment. 26. Subjects with any history of ocular malignancy. 27. Subjects with a clinically significant cardiac disease on routine clinical examination (history, physical examination), or known congestive heart failure, myocardial infarction, clinically significant valvular heart disease, clinically significant cardiac rhythm or conduction abnormalities. 28. Subjects with unstable/uncontrolled hypertension, defined by national recommendations. 29. Subjects with pulmonary dysfunction or severe obstructive pulmonary disease. 30. Subjects with active tuberculosis. 31. Subjects with liver or renal insufficiency. 32. Subjects with unstable endocrine disease, including unstable diabetes or thyroid disease. 33. Subjects with active Hepatitis B or Hepatitis C. 34. Subjects with clinically active infection of herpetic diseases, including herpes simplex virus, varicella zoster virus (VZV), cytomegalovirus (CMV) or EBV. 35. Subjects with known history of ocular infection with herpes simplex virus. 36. Subjects with active (extraocular) infection (requiring or not the prolonged or chronic use of antimicrobial agents). 37. Immunocompromised subjects with previous solid organ or bone marrow transplant. 38. Subjects who receive a live vaccine less than 4 weeks prior to SPVN06 injection 39. Subjects who were infected by COVID-19 less than 2 weeks prior to SPVN06 injection. 40. Subjects who have recently received (less than 4 weeks) or plan to receive a COVID-19 vaccination. 41. Incapacitated subjects, as defined by national laws.

Inclusion Criteria

Exclusion Criteria

1. Able to give signed informed consent and comply with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
2. Age ≥18 years at the time of ICF signature.
3. Subjects of either gender previously diagnosed with advanced RCD due to biallelic mutations in the rod cGMP phosphodiesterase 6 beta (PDE6B) or rod cGMP phosphodiesterase alpha (PDE6A) genes, or due to a monoallelic dominant mutation in the rhodopsin (RHO) gene. The genotyping results must be documented before the initiation of the Screening Visit. Subjects should be retested by the investigator if their genotyping tests were not performed within the 7 previous years, or if they were not performed by an accredited laboratory. In this case, the screening period can be prolonged for 2 additional weeks to allow time to generate genotyping results.
4. Advanced stage is defined as a stage of the natural history of the disease where both distance visual acuity and visual field are affected in both eyes. Substages within the advanced stage are defined as follows (monocular measurements, horizontal axis of isopter III4e for the visual field):
* Severe stage is defined by both a BCVA below or equal to 20/200 and above or equal to 20/800, and a visual field below or equal to 20 degrees (subjects of Cohorts 1 to 3)
* Intermediate stage is defined by both a BCVA below or equal to 20/40 and above 20/200, and a visual field below or equal to 20 degrees (subjects of Cohorts 4 to 6)
5. For subjects with severe advanced RCD enrolled in Step 1 only, the difference in visual acuity between the two eyes of a given subject should be equal to or below 0.3 logarithm of the minimal angle (LogMAR) (≤3 ETDRS lines), with a tolerance margin of 3 ETDRS letters.
6. Clinical diagnosis of RCD based on past medical and family history, mid-peripheral visual field dysfunction, photopsia, night blindness (nyctalopia), and fundoscopic appearance (including but not restricted to bone spicule pigmentation, attenuation of the retinal vessels, and waxy pallor of the optic nerve).
7. Diagnosis of RCD is confirmed on prior full-field ERG (any previously performed ERG is acceptable).
8. Documented preservation of cone inner and outer segments considered good enough by the investigator for the subject to be included in the study.
9. Negative serum pregnancy test for women of childbearing potential (please refer to Schedule of Assessments for details).
10. Women of childbearing potential (WOCBP) and men and/or their partner(s) of childbearing potential must agree to use a highly effective contraceptive method. This applies to the time period between ICF signature and 12 months after SPVN06 subretinal injection SRI (i.e., no longer applicable to subjects of Cohort 4 after randomization). The definition of highly effective contraceptive methods follows CTFG recommendations. Highly effective contraceptive methods are limited to:
* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
* Oral
* Intravaginal
* Transdermal
* Progestogen-only hormonal contraception associated with inhibition of ovulation:
* Oral
* Injectable
* Implantable
* Intrauterine device (IUD)
* Intrauterine hormone-releasing system (IUS)
* Bilateral tubal occlusion
* Vasectomized partner
* Sexual abstinence
11. Subjects must be affiliated to a health security system, if they are included in a clinical site based in France (per law).
12. No out-of-range values for clinical laboratory tests, however, if outside, must be considered as non-clinically relevant by the investigator using a multidisciplinary approach and compatible with a participation in the clinical study.
13. 12-lead electrocardiogram within normal limits, however, when outside, must be documented by the investigator using a multidisciplinary approach as not clinically relevant and compatible with a participation in the clinical study. Nota bene: This criterion of eligibility is only applicable to subjects assigned to a treatment cohort (Cohorts 1, 2, 3, 5, or 6), and is not required to authorize randomization in Step 2.
14. Physical examination without any clinical findings of clinical relevance (per medical/anesthesia staffs judgment) that could compromise participation in the clinical study or could affect the collection and/or evaluation of the study parameters. The findings of clinical relevance considered as contraindications to SPVN06 treatment include, but are not limited to, pulmonary pathology such as COPD, asthma, cardiac conditions such as congestive heart failure or valve disease, renal issues such as renal insufficiency and endocrine issues such as diabetes.

1. Subjects with prior administration of any gene therapy or any previous treatment with stem cell therapy for ocular or non-ocular disease.
2. Subjects participating in another clinical trial and receiving an investigational medicinal product (IMP) within 5 half-lives or 90 days prior to the injection of SPVN06.
3. Subjects with RCD due to any mutation in genes other than those listed in the inclusion criteria.
4. Subjects with systemic disease or other pathology not related to their diagnosis of RCD, and whose symptoms or associated treatments may affect vision, for example cancers or pathology of the central nervous system.
5. Subjects with narrow irido-corneal angles or any other medical situation contraindicating pupillary dilation.
6. Subjects known to be allergic to any of the delivery vehicle constituents or to any other drugs planned to be used during the clinical study.
7. Subjects with known allergies to corticosteroids, or who will be unable to tolerate the corticosteroid regimen as described in the protocol
8. Subjects with systemic disease or other medical or psychiatric conditions that preclude safe participation in the study.
9. Subjects receiving immunosuppressive therapies, other than the immune modulating regimen described in this protocol, or any other therapy known to influence the immune system including but not limited to steroid implants, cytostatics, interferons, tumor necrosis factor (TNF)-binding proteins, drugs acting on immunophilins, or antibodies with known impact on the immune system.
10. Subjects of reproductive potential unwilling to use effective contraception starting right after ICF signature and for 12 months after SPVN06 SRI (i.e., no longer applicable to subjects of Cohort 4 after randomization).
11. Subjects who are pregnant or breastfeeding.
12. Subjects who are unwilling or unable (based on the investigator's judgment) to comply with the study protocol.
13. Subjects with any condition that would not allow them to complete follow-up examinations during the study and, in the opinion of the investigator, would make them unsuitable for the study.
14. Subjects positive for human immunodeficiency virus (HIV) or any other systemic immunocompromising disease.
15. Subjects who have undergone, within 6 months before inclusion, any significant ocular surgery (per investigator's judgment) that could interfere with the evaluation of SPVN06 study objectives.
16. Presence of eye disorders that could interfere with the assessment of visual acuity and/or any other ocular assessments, including SD-OCT, during the study.
17. Presence of any systemic or ocular diseases, other than non-syndromic retinitis pigmentosa (RP), that can cause vision loss.
18. Prior vitrectomy or vitreomacular surgery.
19. Presence of vitreomacular adhesion or traction, epiretinal membrane macular pucker or macular hole, evident by ophthalmoscopy and/or SD-OCT examinations and assessed by the investigator to significantly affect central vision.
20. Current evidence of retinal detachment assessed by the investigator to significantly affect central vision.
21. Active ocular inflammation or recurrent history of idiopathic or autoimmune-associated uveitis.
22. Subjects with presence of any suspected or active ocular or periocular infection (conjunctivitis, keratitis, scleritis, endophthalmitis).
23. Subjects with history of glaucoma.
24. Subjects with uncontrolled intraocular pressure (IOP).
25. Subjects with active cancer or currently receiving any therapy for cancer treatment.
26. Subjects with any history of ocular malignancy.
27. Subjects with a clinically significant cardiac disease on routine clinical examination (history, physical examination), or known congestive heart failure, myocardial infarction, clinically significant valvular heart disease, clinically significant cardiac rhythm or conduction abnormalities.
28. Subjects with unstable/uncontrolled hypertension, defined by national recommendations.
29. Subjects with pulmonary dysfunction or severe obstructive pulmonary disease.
30. Subjects with active tuberculosis.
31. Subjects with liver or renal insufficiency.
32. Subjects with unstable endocrine disease, including unstable diabetes or thyroid disease.
33. Subjects with active Hepatitis B or Hepatitis C.
34. Subjects with clinically active infection of herpetic diseases, including herpes simplex virus, varicella zoster virus (VZV), cytomegalovirus (CMV) or EBV.
35. Subjects with known history of ocular infection with herpes simplex virus.
36. Subjects with active (extraocular) infection (requiring or not the prolonged or chronic use of antimicrobial agents).
37. Immunocompromised subjects with previous solid organ or bone marrow transplant.
38. Subjects who receive a live vaccine less than 4 weeks prior to SPVN06 injection
39. Subjects who were infected by COVID-19 less than 2 weeks prior to SPVN06 injection.
40. Subjects who have recently received (less than 4 weeks) or plan to receive a COVID-19 vaccination.
41. Incapacitated subjects, as defined by national laws.

Contacts and Locations

Study Contact

SparingVision

CONTACT

+33143462060

info@sparingvision.com

Medical Director

CONTACT

Study Locations (Sites)

Bascom Palmer Eye Institute/University of Miami

Miami, Florida, 33136

United States

Casey Eye Institute

Portland, Oregon, 97239

United States

UPMC Eye Center

Pittsburgh, Pennsylvania, 15213

United States

Collaborators and Investigators

Sponsor: SparingVision

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-04-12

Study Completion Date2029-03

Study Record Updates

Study Start Date2023-04-12

Study Completion Date2029-03

Terms related to this study

Keywords Provided by Researchers

RHO
PDE6A
PDE6B
Pathogenic Mutation
Retinal Disease
Eye Disease
Rod-Cone Dystrophy
Gene Therapy
Retinal Dystrophies
Retinal Degeneration

Additional Relevant MeSH Terms

Retinitis Pigmentosa