Safety of Single and Repeat Dose of PYC-001 Eye Injections in People With Autosomal Dominant Optic Atrophy

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-30

Study Completion Date

2027-01-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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 UK and Australia are expected to be enrolled, depending on safety review committee (SRC) throughout the course of the study.

Participants may be assigned to any of the following:

1. A single 60ug dose of PYC-001
2. Three doses of 10ug PYC-001 at an interval of 8 weeks
3. Three doses of 10ug PYC-001 at an interval of 12 weeks
4. Three doses of 30ug PYC-001 at an interval of 8 weeks
5. Three doses of 30ug PYC-001 at an interval of 12 weeks

Following completion of the 4 week safety review of the single 60ug of PYC-001 cohort, and if the 60 μg dose level is deemed safe by the SRC, the following cohorts will also be available:
6. Three doses of 60ug PYC-001 at an interval of 8 weeks
7. Three doses of 60ug PYC-001 at an interval of 12 weeks

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

SAD of IVT PYC-001 in OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy (Sundew)

NCT06461286

OPA1 Gene Mutation Autosomal Dominant Optic Atrophy Hereditary Optic Atrophies +1 more

ACTIVE_NOT_RECRUITING PHASE1

A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001

NCT06852963

Retinitis Pigmentosa 11 Retinal Degeneration Retinal Disease +2 more

RECRUITING PHASE1/PHASE2

Study of Efficacy and Safety of Voretigene Neparvovec in Japanese Patients With Biallelic RPE65 Mutation-associated Retinal Dystrophy

NCT04516369

Biallelic RPE65 Mutation-associated Retinal Dystrophy

ACTIVE_NOT_RECRUITING PHASE3

SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects

NCT05902962

Retinal Dystrophy PRPF31 Mutationassociated Retinal Dystrophy RP11

ACTIVE_NOT_RECRUITING PHASE1

A Phase I/II Dose-escalating Study of the Safety, Tolerability and Efficacy of KIO-301 Administered Intravitreally to Patients With Retinitis Pigmentosa and Choroideremia (ABACUS)

NCT05282953

Retinitis Pigmentosa Choroideremia Non-Syndromic Rod-Dominant Inherited Retinal Diseases

RECRUITING PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

OPA1 Gene Mutation Autosomal Dominant Optic Atrophy Hereditary Optic Atrophies Kjer Optic Atrophy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

PYC-001

PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. 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;
2. Adult males and females, aged 18 years and above at screening;
3. Body mass index ≥18.0 and ≤35.0 kg/m2
4. Have a recent (within five years) genetic diagnosis of OPA1 mutation-associated (haploinsufficiency) ADOA and/or confirmed diagnosis during pre-screening or 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;
5. 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 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. In the event that both eyes are eligible and have adequate fixation to reliably perform all study assessments, the worse eye as determined by the physician will be taken as the study 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;
6. 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), specifically the outer ring (T, TS, NS, N, NI and TI), defined as:

1. Mild disease = RNFL abnormalities (outside normal range) in no more than one of six sectors;
2. Moderate disease = RNFL abnormalities (outside normal range) in no more than three of six sectors;
3. Severe disease = RNFL abnormalities (outside normal range) in four of six sectors;
4. Advanced disease = RNFL abnormalities (outside normal range) in six of six sectors;
7. 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):

1. Physical examination without any clinically relevant findings;
2. Systolic blood pressure (BP) in the range of 90 to 160 mmHg and diastolic BP in the range of 50 to 95 mmHg after five minutes in sitting or supine or semi-supine position;
3. Heart rate (HR) in the range of 45 to 110 bpm after five minutes rest in sitting or supine or semi-supine position;
4. Body temperature (tympanic), between 35.5°C and 37.7°C;
5. No clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening .
8. Female participants must be of non-childbearing potential, i.e., 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:
1. Have a negative pregnancy test at the screening visit and on study Day -1;
2. Agree not to attempt to become pregnant or donate ova from signing of the consent form until at least 130 days after final IVT dose administration of PYC-001;
3. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 130 days after final IVT dose administration of PYC-001 , if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
9. Male participants must:

1. Agree not to donate sperm from signing the consent form until at least 190 days after final IVT dose administration of PYC-001;
2. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception (defined in Appendix 13.1) from signing the consent form until at least 190 days after final IVT dose administration of PYC-001;
3. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 190 days after final IVT dose administration of PYC-001 and;
10. Willing and able to comply with all study assessments and protocol schedule/ restrictions

Exclusion Criteria

1. Participant has a known allergy to PYC-001 or any of its excipients;
2. 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;
3. Females who are breastfeeding or planning to breastfeed;
4. 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;
5. Have received any prior cell or gene therapy for a retinal condition, excluding participation in study PYC-001-101;
6. 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.
7. 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;
8. 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;
9. Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, as assessed by the PI in the study eye ;
10. Macular edema (intraretinal, sub-retinal or other fluid) in the study eye requiring treatment.
11. History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation;
12. Have used within 30 days of the Screening visit or is using any investigational drug (excluding PYC-001 from participation in PYC-001-101) or over-the-counter drug such as Idebenone, Vitamin B6, Vitamin B12, 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;
13. 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;
14. 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;
15. Positive alcohol breath test as assessed at screening, and on study Day -1 and study Day 1;
16. Positive urine drugs of abuse as assessed at screening and on study Day -1 and study Day 1;
17. 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;
18. 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;
19. Positive test for human immunodeficiency virus, hepatitis B or C virus;
20. Clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening, defined as:

* Alanine transaminase (ALT) or aspartate aminotransferase (AST) \>2 × upper limit of normal (ULN) or bilirubin \>1.5 × ULN (unless patient has Gilbert's syndrome);
* Estimated glomerular filtration rate \<60 mL/min/1.73 m2; Australia, Version 3.0, 12 JUN 2025 44 Confidential
* Hemoglobin A1c level ≥7.0%;
* International normalized ratio ≥1.2;
* Hemoglobin \<10 g/dL, platelets \<100,000/μL, and white blood cells within the normal range;
* Clinically significant abnormalities in the urine analysis.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No