Section 4 of 6
Clinical evidence
62 evidence topics · 23 sources
Study summaries
DRAGON
Objective
Location and study date
Original UK protocol: ethics opinion
| Field | Quoted record |
|---|---|
| Ethics opinion date | “25 Nov 2021” |
| Ethics committee | “Wales REC 5” |
Completion of the final study visit
Study design
Eligibility criteria
DRAGON pivotal phase 3 trial: enrollment criteria
Treatment
DRAGON pivotal phase 3 trial: treatment groups
Study outcomes
Rationale for using DDAF lesion growth as the primary endpoint
Primary endpoint and reported regulatory agreement
Planned patient-reported assessments
Visual-acuity endpoint: natural-history rate of change
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
Modified full analysis set: baseline and post-baseline requirements
Results
Participant disposition
DRAGON pivotal phase 3 trial: treatment-related discontinuations
Baseline characteristics
Efficacy results
DRAGON: primary-endpoint results
| Endpoint, population, treatment, or analysis | Source quotation |
|---|---|
| “DDAF” | “Study Eye” |
| “mFAS” | “N = 96” |
| “Tinlarebant 5 mg” | “0.38 mm²/year” |
| “Placebo” | “0.59 mm²/year” |
| “treatment effect size” | “35.7%” |
| “unstructured covariance matrix” | “P = 0.0033” |
DRAGON pivotal phase 3 trial: visual acuity
DRAGON quantitative autofluorescence secondary endpoint: tinlarebant
DRAGON quantitative autofluorescence secondary endpoint: placebo
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
DRAGON pivotal phase 3 trial: adverse events
DRAGON pivotal phase 3 trial: serious non-ocular treatment-emergent adverse events
Non-ocular adverse events: safety population
| Category | Tinlarebant 5 mg, 69 participants | Placebo, 35 participants |
|---|---|---|
| Any non-ocular TEAE | “59 (85.5%)” | “27 (77.1%)” |
| Serious non-ocular TEAE | “2 (2.9%)” | “4 (11.4%)” |
| Drug-related non-ocular TEAE | “14 (20.3%)” | “4 (11.4%)” |
| Non-ocular TEAE resulting in study-drug discontinuation | “0 (0.0%)” | “0 (0.0%)” |
Ocular adverse events: safety population
| Category | Tinlarebant 5 mg, 69 participants | Placebo, 35 participants |
|---|---|---|
| Any ocular TEAE | “53 (76.8%)” | “8 (22.9%)” |
| Drug-related ocular TEAE | “49 (71.0%)” | “8 (22.9%)” |
| Serious ocular TEAE | “0 (0.0%)” | “0 (0.0%)” |
| Ocular TEAE resulting in study-drug discontinuation | “4 (5.8%)” | “0 (0.0%)” |
| Ocular TEAE resulting in study discontinuation | “2 (2.9%)” | “0 (0.0%)” |
Study limitations
Summary
DRAGON enrolled 104 participants aged 12–20 years with defined atrophic lesions and visual acuity of 20/200 or better. Its modified full analysis set included 96 participants, rather than all randomized participants. The primary outcome was anatomical lesion growth; minimal visual-acuity change in both groups limits conclusions about functional benefit during the 24-month treatment period. These eligibility restrictions also limit direct applicability to younger children and participants outside the studied lesion-size and visual-acuity ranges.
DRAGON II
Objective
Location and study date
UK protocol: ethics opinion
| Field | Quoted record |
|---|---|
| Ethics opinion date | “14 Jun 2024” |
| Ethics committee | “Wales REC 3” |
Study design
DRAGON II phase 1b and phase 2/3 trials: randomization
DRAGON II phase 1b and phase 2/3 trials: study duration and visits
Design of the phase 1b and phase 2/3 components
| Component and feature | Quoted record |
|---|---|
| Phase 1b masking | “open-label” |
| Phase 2/3 masking | “double-masked” |
| Phase 2/3 treatment duration | “24-month” |
Eligibility criteria
DRAGON II phase 1b and phase 2/3 trials: inclusion criterion
DRAGON II phase 1b and phase 2/3 trials: age range
DRAGON II phase 1b and phase 2/3 trials: exclusion criterion
Treatment
Study outcomes
Rationale for using atrophic lesion growth as the primary endpoint
Primary efficacy outcome and safety assessments
Trial-specific endpoint-validation analysis
No evidence found.
Statistical analysis description
Number of participants (Planned and analyzed)
DRAGON II phase 1b and phase 2/3 trials: enrollment
Description of analysis sets
No evidence found.
Results
Participant disposition
No evidence found.
Baseline characteristics
No evidence found.
Efficacy results
No evidence found.
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
No evidence found.
Study limitations
Summary
The available update establishes enrollment of 73 participants, including 15 Japanese participants, in the phase 2/3 component. The evidence collected here describes its design and eligibility rather than treatment-effect estimates or completed safety results. Its age range of 12–20 years and requirement for clinically diagnosed STGD1 with an identified ABCA4 mutation constrain the population to which future findings can directly apply.
LBS-008-CT02
Objective
Location and study date
Study design
Phase 1b/2 dose-finding and two-year extension: design
Eligibility criteria
Phase 1b/2: adolescent age range
Treatment
Phase 1b/2: oral regimen
Study outcomes
Rationale for using systemic and ocular safety and tolerability as the primary endpoint
Not applicable.
Statistical analysis description
Number of participants (Planned and analyzed)
Phase 1b/2 dose-finding and two-year extension: enrollment
Description of analysis sets
External natural-history comparison population
Results
Participant disposition
Phase 1b/2 dose-finding and two-year extension: adverse-event withdrawals
Baseline characteristics
Efficacy results
Phase 1b/2 dose-finding and two-year extension: 24-month results
Phase 1b/2 dose-finding and two-year extension: additional analysis
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
Study limitations
Summary
The supporting study was open-label and enrolled 13 participants. Its 24-month lesion result was reported for 12 participants, and the visual-acuity analysis concerned a subgroup of 6 with prior bilateral visual loss. The natural-history comparison used selected ProgStar participants rather than a concurrently randomized placebo group. These design features and small denominators limit causal interpretation of lesion and visual-acuity findings. The reported genotype distribution, with severe pathogenic or likely pathogenic ABCA4 variants in 11 participants (85%), further describes the selected study population.
LBS-008-CT09
Objective
Location and study date
Recruitment location and actual study dates
| Field | Quoted record |
|---|---|
| Site | “CMAX Clinical Research Pty Ltd - Adelaide” |
| First participant enrollment | “7/01/2024” |
| Last participant enrollment | “31/05/2024” |
| Last data collection | “5/07/2024” |
Study design
Registry: overall allocation
Registry: food-effect treatment sequences
Eligibility criteria
Study population
Registered age limits
| Criterion | Quoted record |
|---|---|
| Minimum age | “18 Years” |
| Maximum age | “65 Years” |
Treatment
Tinlarebant dose
Perpetrator-drug regimens
| Drug | Quoted regimen |
|---|---|
| Omeprazole | “40 mg QD” |
| Itraconazole | “200 mg BD” |
| Rifampin | “600 mg QD” |
Study outcomes
Rationale for using cmax and AUCinf as the primary pharmacokinetic endpoints
Not applicable.
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
Analysis-set membership and exclusions
No evidence found.
Results
Participant disposition
No evidence found.
Baseline characteristics
No evidence found.
Efficacy results
Drug-interaction pharmacokinetic results
Food-effect pharmacokinetic results
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
Study limitations
Summary
This pharmacokinetic study enrolled 49 healthy adult participants and evaluated single-dose tinlarebant exposure with selected interacting drugs or food. Its exposure ratios do not establish long-term clinical efficacy in Stargardt disease. The registry records a non-randomized trial overall, whereas the publication describes a randomized, open-label, two-period interaction study; the registry’s food-effect component specifies randomized fed/fasted sequences. These descriptions should not be interpreted as a randomized comparison of all perpetrator-drug groups.