Complement Therapeutics GmbH (CTx) announced the first patient has received dosing in its first-in-human (FIH) clinical trial evaluating CTx001, its investigational gene therapy, among patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
This news follows 6 months after the FDA gave the green light for the investigational new drug (IND) study’s kick off.
Nice! First thing’s first: Catch me up to speed on things.
For the sake of brevity, see here for everything to know about CTx, its scientific focus, and the company’s Complement Precision Medicine (CPM) Platform.
Now to this gene therapy.
To be more specific: CTx001 is an adeno-associated virus (AAV)-based gene therapy that delivers a truncated version of complement receptor 1 (mini-CR1) via a single subretinal injection.
Through this injection, the intent is to enable a long-term modulation of the complement cascade’s classical and alternative pathways that enables a sustained effect.
- As for its regulatory status: While still investigational (hence this FIH trial), CTx001 was granted Fast Track designation from the FDA just a few months ago.
- See the advantages that come with this designation.
Next up: this study.
Dubbed Optimized Geographic Atrophy INterventional (Opti-GAIN), the phase 1/2 clinical trial (NCT07392255) is evaluating the safety, tolerability, and preliminary efficacy of CTx001 as a subretinally-administered injection.
While we don’t know the estimated number of participants, Clinical Trials offers a look at the eligibility criteria. In general, patients must be aged 55+ with bilateral GA secondary to AMD.
And its setup?
Conducted by a United Kingdom-based subsidiary of CTx, Opti-GAIN is divided into two parts:
- Part 1: An open-label, dose-escalation study across three dose cohorts
- Cohort 1: Low dose CTx001
- Cohort 2: Medium dose CTx001
- Cohort 3: Low dose CTx001
- Part 2: A dose-expansion
- Cohort 4: An expansion of a dose selected from Cohorts 1-3
- Cohort 5: An expansion of a second dose selected from Cohorts 1-3
Let’s talk outcome measures.
The study is evaluating one primary objective and seven secondary objectives.
The primary: Safety and tolerability of a single CTx injection at three dose levels, as measured by ocular, non-ocular, and serious adverse events (AEs) from dosage to Week 52 (Year 1).
Among the secondary: An evaluation of the preliminary efficacy of CTx001 treatment via Changes in structural and functional GA parameters—based on measuring:
- Sensitivity via microperimetry at Year 1
- Changes in low-luminance visual acuity (LLVA) via Early Treatment Diabetic Retinopathy (ETDRS) chart and neutral density filter at Year 1
- See here for all, ranging in duration from baseline to Year 1 and baseline to Year 2
And in terms of timing … when is the study expected to conclude?
In its entirety (parts 1 and 2), Clinical Trials estimates a primary completion (in which the last patient will be examined) of May 31, 2028, followed by a study completion of June 30, 2032.
- However, no specifics are available yet regarding the conclusion of Part 1.
Gotcha. Now, isn’t there another trial we should be aware of as well?
Indeed there is … that would be the Pre-GAIN trial (NCT07144137), an ongoing, non-interventional natural history study observing short-term progression in GA.
What we know about it: The multi-center trial is identifying an estimat 75 patients with progressive GA to measure structural and functional parameters characterizing GA progression—and investigate a potential correlation with genetic or lifestyle factors.
- Its status: The study kicked off last summer and is currently enrolling participants across the United States and the UK.
- See here details on its participants, setup, and outcome measures.
And how will Pre-GAIN be used in CTx’s research?
Both Opti-GAIN and the natural history study are intended to support patient selection and the evaluation of key structural and functional endpoints, such as:
- Ellipsoid zone
- Focal optical coherence tomography (OCT)-based microperimetry
Per CTx CEO Rafiq Hasan, MBBS: “By advancing Opti-GAIN alongside Pre-GAIN, we are generating natural history and interventional data to better inform patient selection, endpoint strategy, and future clinical development.”
… and when might we see data from this natural history study?
Hopefully, sooner than Opti-GAIN, as Clinical Trials is reporting the study’s primary (and total) completion timeframe in 2027 (March 31 and June 30, respectively).