Clinical Trials

CHM Clinical Trials

A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111

NCT: NCT03507686
URL: https://clinicaltrials.gov/study/NCT03496012
Intervention: DRUG: BIIB111

Technical Summary: At 12 months, VA was generally maintained in both eyes following bilateral sequential subretinal injection of BIIB111. Across 66 participants, the mean BCVA change was small and not clinically significant (–2.8 letters +/- 16.0 SD) despite both eyes undergoing retinal detachment and subretinal injection. No meaningful deterioration was observed in microperimetry, autofluorescence, or OCT structure at month 12. Safety outcomes showed low rates of serious surgical complications (7.6%), mostly mild-to-moderate inflammation manageable with steroids. Retinal inflammation occurred in 45% of participants but was not correlated with significant vision loss. Importantly, no systemic immune reactions or additive toxicity were seen between the first and second eye. Overall, the study supports that bilateral gene therapy is feasible and well-tolerated, providing evidence that prior AAV2 exposure does not preclude safe sequential treatment.

Lay Language Summary: After one year, participants in the study generally maintained their vision in both eyes after receiving the BIIB111 gene therapy in each eye, one after the other. Among the 66 participants, the average change in visual acuity was very small and not considered clinically meaningful, even though both eyes went through a controlled retinal detachment and subretinal injection as part of the procedure. Other measures of vision and retinal health, including light sensitivity testing, autofluorescence imaging, and OCT scans, also stayed stable over the 12-month period. The treatment’s safety profile was encouraging. Serious surgical complications were uncommon, occurring in about 8 percent, and most inflammation was mild to moderate and responded well to steroid treatment. Retinal inflammation occurred in nearly half of participants but did not lead to significant vision loss. There were no signs of harmful immune reactions in the body, and treating the second eye did not add any safety concerns. Overall, the results suggest that treating both eyes with this type of gene therapy is possible and generally safe, and that previous exposure to the AAV2 vector does not prevent safe treatment of the second eye.

Efficacy and Safety of BIIB111 for the Treatment of Choroideremia

NCT: NCT03496012
URL: https://clinicaltrials.gov/study/NCT03496012
Intervention: GENETIC: BIIB111

Technical Summary: In this phase 3 trial, patients with choroideremia received a single subretinal injection of BIIB111 at either high dose (1.0×10¹¹ vg; n=69) or low dose (1.0×10¹⁰ vg; n=34) versus a no-treatment control (n=66). At 12 months, the study did not meet the primary endpoint: ≥15-letter BCVA gains occurred in 5% (3/65) of high-dose, 3% (1/34) of low-dose, and 0% (0/62) of controls; key secondary endpoints were therefore not tested for significance, though ≥10-letter gains were seen in 14–18% of treated eyes vs 2% of controls. Safety was largely ocular and manageable: most adverse events were mild/moderate; in the lay summary safety set (n=164), any AE occurred in 91–94% of treated participants vs 51% of controls, serious AEs in 17–26% vs 15%, and no deaths were reported which is consistent with vitrectomy/subretinal procedures.Overall, STAR shows that while subretinal BIIB111 was generally tolerable, it failed to demonstrate efficacy on BCVA at 12 months in this pivotal setting.

Lay Language Summary: In this Phase 3 study, people with choroideremia received a single injection of the gene therapy BIIB111 under the retina. Participants received either a high dose, a low dose, or no treatment. After one year, the main goal of the study, significant improvement in vision, was not met. A small number of treated participants did experience noticeable vision gains, and slightly more people in the treated groups had smaller improvements compared with the no-treatment group.The treatment was generally safe. Most side effects were related to the eye and were mild to moderate, and serious side effects were uncommon. No deaths occurred, and the safety profile was similar to what is expected with this type of eye surgery. Overall, this study showed that BIIB111 injections under the retina were generally well tolerated but did not significantly improve vision after 12 months in this trial.

Safety and Dose-Escalation Study of AAV2-hCHM in Participants With CHM (Choroideremia) Gene Mutations

NCT: NCT02341807
URL: https://clinicaltrials.gov/study/NCT02341807study data
Intervention: BIOLOGICAL: AAV2-hCHM
Sponsor: Spark Therapeutics

Technical Summary: The 2-year interim results showed no significant loss or gain in vision in treated eyes for most patients. Best-corrected visual acuity (BCVA) remained within 15 letters of baseline in 13 of 15 treated eyes, indicating stable vision over that period. No serious treatment-related adverse events were reported; the therapy was generally well-tolerated. Mild procedure-related complications were noted in a couple of cases (e.g. one case of foveal thinning and one macular hole), suggesting some surgical risk to the fragile retina. Overall, the trial demonstrated safety of the subretinal gene therapy and maintenance of visual function, but no dramatic efficacy signal (no significant improvement in acuity) at 2 years.

Lay Language Summary: The two-year results showed that most participants maintained their vision in the treated eyes. Vision stayed within a small range of baseline levels in 13 out of 15 treated eyes, showing that eyesight remained stable over this period. The treatment was generally safe and well tolerated. No serious side effects related to the therapy were reported. A few mild procedure-related issues occurred, including one case of thinning in the central retina and one macular hole, which shows that there is some surgical risk for the delicate retina. Overall, the study showed that the subretinal gene therapy was safe and helped maintain vision, but it did not lead to significant improvements in eyesight after two years.

Dose Escalation Study of Intravitreal 4D-110 in Patients With Choroideremia

NCT: NCT04483440
URL: https://clinicaltrials.gov/study/NCT04483440
Intervention: BIOLOGICAL: Injection of AAV2-REP1 (10e11 vg)
Sponsor: 4D Molecular Therapeutics

Technical Summary: This study will evaluate safety, tolerability, and preliminary efficacy of a single intravitreal (IVT) injection of a recombinant adeno-associated virus (AAV) gene therapy, 4D-110, in male patients with genetically-confirmed Choroideremia (CHM).  This is an open-label, Phase 1 study to evaluate safety and tolerability as well as preliminary efficacy of a single IVT injection of 4D-110 at three dose levels in male patients with genetically-confirmed CHM. 13 patients were enrolled and are currently being monitored. The study is estimated to be completed in 2027.

Lay Language Summary: This study is testing the safety and early signs of effectiveness of a gene therapy called 4D-110. The treatment is given as a single injection into the eye. Only males with genetically confirmed choroideremia are included. This is a Phase 1 study, which means the main goal is to understand whether the treatment is safe and how well people tolerate it. Researchers are also looking for any early changes or improvements in vision. Thirteen participants have enrolled and are being monitored. The study is expected to finish in 2027.

Choroideremia Gene Therapy Clinical Trial

NCT: NCT02553135
URL: https://clinicaltrials.gov/study/NCT02553135
Intervention: BIOLOGICAL: Injection of AAV2-REP1 (10e11 vg)

Byron Lam, MD, Professor of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, United States

Technical Summary: At 24 months, visual acuity improved by an average of 3 letters (SD = 4) in treated eyes following a single subretinal injection of AAV2-REP1, indicating a mild but meaningful gain in central vision stability or improvement. This phase 2 open-label trial demonstrated that patients who received the gene therapy generally maintained or improved VA, while untreated control eyes showed the expected gradual decline seen in natural history. The microperimetry results showed localized improvements in retinal sensitivity near the treated area, suggesting functional recovery in photoreceptors adjacent to the injection zone. Similarly, fundus autofluorescence imaging revealed preserved or slightly expanded areas of viable RPE, indicating that structural integrity was maintained or protected over the follow-up period.

Lay Language Summary: After two years, participants who received a single subretinal injection of AAV2-REP1 experienced an average improvement of 3 letters in their vision. This shows a small but meaningful gain or stability in central vision. In this Phase 2 study, patients who received the gene therapy generally maintained or improved their vision, while untreated eyes showed the gradual decline that is normally expected in choroideremia. Testing of retinal sensitivity near the treated area showed some localized improvements, suggesting that the cells in that part of the retina were functioning better. Imaging of the retina also showed that important retinal structures were preserved or slightly expanded, indicating that the therapy helped maintain or protect the health of the retina over the two-year follow-up period.

In Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia

NCT: NCT02077361
URL: https://clinicaltrials.gov/study/NCT02077361
Intervention: GENETIC: rAAV2.REP1 vector (1×10¹¹ vg)
Principal Investigator: Ian M. MacDonald, MD, CM, Professor of Ophthalmology, Canada

Technical Summary: This phase I Alberta Ocular Gene Therapy Team trial assessed safety and exploratory efficacy in six adult males (ages 30–42) with genetically confirmed CHM. The worse-seeing eye of each subject received a single 0.1 mL subfoveal injection of rAAV2.REP1. Most treated eyes maintained stable vision; one patient improved by 15+ letters, while others showed no meaningful change. Microperimetry revealed no significant functional gain, though treated eyes tended to retain baseline sensitivity over two years. Fundus autofluorescence showed a linear RPE decline (~8%/year) parallel in treated and untreated eyes. They also talked about how VA is not a good endpoint for CHM clinical trials.

Lay Language Summary: This Phase 1 study by the Alberta Ocular Gene Therapy Team tested safety and early signs of effectiveness in six adult males with genetically confirmed choroideremia, ages 30 to 42. The eye with worse vision in each participant received a single small injection of the gene therapy rAAV2.REP1 under the central retina. Most treated eyes maintained stable vision over two years. One participant experienced a noticeable improvement of 15 letters or more, while the others showed little change. Testing of retinal sensitivity showed no significant gains, but treated eyes generally kept their baseline sensitivity. Imaging of the retina showed a steady decline in certain retinal cells at a rate similar to untreated eyes, about 8 percent per year. The study also noted that measuring changes in visual acuity may not be the best way to assess outcomes in CHM clinical trials.

THOR – Tübingen Choroideremia Gene Therapy Trial

NCT: NCT02671539
URL: https://clinicaltrials.gov/study/NCT02671539
Intervention: GENETIC: rAAV2.REP1 (1×10¹¹ gp in 0.1 mL)
Principal Investigator: Manuel D. Fischer, MD, PhD,Centre for Ophthalmology, University Hospital Tübingen, Germany

Technical Summary: Each patient (14) received treatment in one eye, with the fellow eye serving as a control, and was followed for 24 months. Visual acuity outcomes were variable. Some participants experienced letter gains up to +15 on the EDTRS scale, while others had minimal or no change, reflecting baseline disease variability. Microperimetry and fundus autofluorescence demonstrated structural and functional preservation trends, particularly in eyes treated at earlier disease stages. Mentions the trial being too short to tell if it changed progression, but there are promising results.

Lay Language Summary: In this study, 14 participants received gene therapy in one eye, while the other eye was not treated and served as a control. They were followed for two years. Results for vision were mixed. Some participants gained up to 15 letters on the vision chart, while others had little or no change. This reflects the natural differences in disease severity among patients. Tests of retinal function and imaging showed trends toward preserving both structure and function, especially in eyes treated at earlier stages of the disease. The study was too short to determine whether the therapy changes the long-term course of choroideremia, but the results are encouraging.

Gene Therapy for Blindness Caused by Choroideremia

NCT: NCT01461213
URL: https://clinicaltrials.gov/study/NCT01461213
Intervention: DRUG: rAAV2.REP1
Study Chair: Robert E. MacLaren, MB ChB DPhil, University of Oxford, Oxford Radcliffe Hospitals NHS Trust and Moorfields Eye Hospital

Technical Summary: In the initial 6-patient cohort, vision generally improved or recovered after the planned macular detachment; notably, two participants with poorer baseline vision gained +21 and +11 ETDRS letters and maintained meaningful benefit on longer follow-up. In the expanded Oxford cohort (n=14), treated eyes showed a median BCVA gain of about +4.5 letters at 24 months (vs –1.5 letters in untreated fellow eyes), with 6/14 gaining >5 letters; reviews summarizing the same program report a median +5.5 ± 6.8 letters across 14 patients. Microperimetry/structure were broadly consistent with functional maintenance over the first two years (FAF area declined at similar rates in treated and fellow eyes) which aligns with a disease-slowing rather than dramatic reversal signal. Safety was acceptable for subretinal gene delivery: adverse events were mainly surgery-related and manageable; the Oxford reports note one serious adverse event and procedure-related complications in a small number of cases, without systemic vector toxicity. Overall, this trial established that rAAV2.REP1 subretinal therapy is feasible and generally well-tolerated, with modest median VA gains and durable improvements in a subset of patients.

Lay Language Summary: In the first group of six participants, vision generally improved or recovered after the planned procedure to detach part of the central retina. Two participants who started with poorer vision gained 21 and 11 letters on the vision chart and maintained meaningful benefits during longer follow-up. In the larger Oxford group of 14 participants, treated eyes showed a median vision gain of about 4.5 letters after two years, while the untreated eyes lost about 1.5 letters. Six out of 14 participants gained more than 5 letters. Reviews summarizing the same program report a median gain of about 5.5 letters across all 14 patients. Tests of retinal function and imaging showed that treated eyes generally maintained function over the first two years. Imaging showed that certain retinal areas declined at similar rates in treated and untreated eyes, suggesting the therapy may slow disease progression rather than dramatically reverse it. The treatment was generally safe for subretinal delivery. Most side effects were related to the surgery and were manageable. Reports note one serious adverse event and a few procedure-related complications, but no harmful effects from the gene therapy itself were seen in the body. Overall, this trial showed that rAAV2.REP1 therapy under the retina is feasible and generally well-tolerated. It led to modest vision gains on average and durable improvements in a subset of patients.

REP1 Gene Replacement Therapy for Choroideremia

NCT: NCT02407678
URL: https://clinicaltrials.gov/study/NCT02407678
Intervention: GENETIC: AAV-mediated REP1 gene replacement up to 1×10¹¹ vector particles
Principal Investigator: Robert E. MacLaren, MB ChB DPhil, University of Oxford, Oxford Radcliffe Hospitals NHS Trust and Moorfields Eye Hospital

Technical Summary: At 24 months, VA remained largely stable in both treated and control eyes, suggesting that while the treatment maintained central vision, no clear efficacy signal was detected. There were 30 participants in this trial. In uncomplicated cases, microperimetry and fundus autofluorescence demonstrated a similar centripetal pattern of degeneration in both eyes, indicating no acceleration or slowing of disease progression. Overall, the study confirmed the therapy’s safety profile but found no statistically significant improvement in VA or retinal sensitivity compared to controls.

Lay Language Summary: After two years, vision remained mostly stable in both the treated and untreated eyes in this study of 30 participants. This suggests that the treatment helped maintain central vision, but there was no clear evidence that it improved vision. In cases without complications, tests of retinal function and imaging showed similar patterns of gradual retinal changes in both eyes, indicating that the therapy did not noticeably slow or speed up disease progression. Overall, the study confirmed that the therapy was safe, but it did not show significant improvement in vision or retinal function compared with the untreated eyes.