Status and phase
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Treatments
About
This study aims to gather safety data and determine the optimal dosing regimen for PYC-001 in participants with confirmed OPA1 mutation-associated ADOA. Approximately 21 participants from across US, UK and Australia are expected to be enrolled, depending on safety review committee throughout the course of the study. Participants may be assigned to any of the following:
Full description
This is a phase 1b open-label, randomized, single and repeat dose study to evaluate the safety and tolerability of IVT administered PYC-001 in participants with confirmed OPA1 mutation-associated ADOA. The primary objective of this study is to gather safety data and determine the optimal dosing regimen for PYC-001. The exploratory objectives of this study include evaluating the ocular structural and functional changes following multiple doses of IVT administered PYC-001. The PK profile of PYC-001 following multiple doses will also be assessed. In this open-label study, PYC-001 will be injected in a single eye and ocular safety will be assessed in both eyes. Approximately 21 participants are expected to enroll and complete this study; the number of enrolled participants may vary and will be driven by decisions made by the safety review committee (SRC) throughout the course of the study.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Must give written informed consent before any study-related activity is carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects;
Adult males and females, aged 18 years and above at screening;
Body mass index ≥18.0 and ≤32.0 kg/m2, with a body weight ≤100 kg at screening;
Have a recent (within five years) genetic diagnosis of OPA1 mutation-associated (haploinsufficiency) ADOA and/or confirmed diagnosis during screening, as determined by the PI. In case of complex mutation profile, eligibility will be determined in consultation with the Sponsor. Rollover participants are exempt from this criterion as their genetic diagnosis was confirmed in PYC-001-101;
Treatment naïve participants with best-corrected visual acuity (BCVA) of between ≤20/40 (≤70 Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) and ≥20/200 (≥35 ETDRS letters). If both eyes meet this eligibility criteria, the eye with better fixation or better vision as determined by the PI in consultation with the Sponsor will be selected as the study eye and the other eye will be designated as the fellow eye. PYC-001-101 participants are exempt from this criterion and will have the same study eye and fellow eye as determined in PYC-001-101;
Treatment Naïve participants (participants from PYC-001-101 are exempt from this criterion) with mild to moderate visual field loss and retinal nerve fiber layer (RNFL) loss in the study eye only as determined by the Spectralis Glaucoma Module Premium Edition (GMPE) RNFL & visual field structure function data (map), defined as:
Medically healthy (in the opinion of the PI), as determined by pre-study medical history, and without clinically significant abnormalities including (assessments may be repeated at the discretion of the PI if an out-of-range value is determined to be erroneous):
Female participants must be of non-childbearing potential, ie, surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least six weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle stimulating hormone [FSH] level consistent with postmenopausal status, per local laboratory guidelines). Females receiving hormone replacement therapy (HRT) may be considered for inclusion if the need for HRT is for no other medical reason than to treat symptoms associated with menopause. If female participants are of childbearing potential, they must:
Male participants must:
Willing and able to comply
Exclusion criteria
Participant has a known allergy to PYC-001 or any of its excipients;
Demonstrated clinically significant co-morbidities, which, in the opinion of the PI, would interfere with the participant's ability to participate in the study and/or confound study outcomes;
Females who are breastfeeding or planning to breastfeed;
Based on recent (within five years of screening [for rollover PYC-001-101 participants, within five years of entry into PYC-001-101]) genetic testing, the participant has mutations in genes that cause ADOA, other than OPA1 (for example in case of dominant negative ADOA and ADOA Plus) or has other pathological variants that result in an ADOA-like optic atrophic phenotype or other pathologic genetic findings indicating presence of additional confounding ocular diseases based on comprehensive genetic screening. Eligibility will be determined by the PI in consultation with the Sponsor as needed;
Have received any prior cell or gene therapy for a retinal condition, excluding participation in study PYC-001-101;
Within three months prior to study Day -1, have undergone any vitreoretinal surgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus or intraocular lens, radial optic neurotomy, sheathotomy, cyclodestructive procedures or multiple filtration surgeries [two or more]) or any other ocular surgery in the study eye. This criterion does not apply for rollover participants from PYC-001-101;
Within three months prior to study Day -1, have placement of an Ozurdex® implant. This criterion does not apply for rollover participants from PYC-001-101;
Within three years prior to study Day -1, have placement of Retisert® of Iluvien® implants. This criterion does not apply for rollover participants from PYC-001-101;
Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, as assessed by the PI in the study eye ;
Macular edema (intraretinal, sub-retinal or other fluid) in the study eye requiring treatment.
History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation;
Have used within 30 days of the Screening visit or is using any investigational drug or over-the-counter drug such as Idebenone or Vitamin B6 or a device which in the opinion of the PI or Sponsor could affect the optic nerve and/or influence functional vision or visual function during the study period. A decision will be made on a case-by-case basis by the PI in consultation with the Sponsor. Participation in observational studies is allowable based on PI discretion and consultation with the Sponsor's Medical Representative. Participation in PYC-001-101 is allowed;
Over-the-counter drugs like CoQ10 and other Nutraceutical usage will require a washout by five half-lives prior to baseline visit. Participants may need to stop taking the drug for the duration of the study based on Physician discretion and in consultation with the Medical Monitor;
Have a recent history (<6 months) of or current excessive recreational drug or alcohol use, in the opinion of the PI. Excessive alcohol use is defined as regular consumption of >10 standard drinks per week or >4 standard drinks per day, where one standard drink is defined as 10 grams of pure alcohol;
Positive alcohol breath test as assessed at screening, and on study Day -1 and study Day 1;
Positive urine drugs of abuse as assessed at screening and on study Day -1 and study Day 1;
Any retinal pathology other than ADOA or any other condition or prior therapy that in the opinion of the PI would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements;
Presence of illness or pathology that, per investigator, include symptoms and/or the associated treatments that can alter visual function. For example, cancers or pathology of the central nervous system, including multiple sclerosis;
Positive test for human immunodeficiency virus, hepatitis B or C virus;
Clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening, defined as:
Primary purpose
Allocation
Interventional model
Masking
21 participants in 7 patient groups
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Central trial contact
Sreenivasu Mudumba
Data sourced from clinicaltrials.gov
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