Table 1 Completed and ongoing clinical trials of rapamycin/everolimus on TSC in the past 15Â years
From: Perfect match: mTOR inhibitors and tuberous sclerosis complex
Drug | Clinical trial accession no | Period | Population | Phase | No. of participants (age) | Status | Primary end point |
|---|---|---|---|---|---|---|---|
Brain | Â | Â | Â | Â | Â | Â | Â |
Rapamycin | NCT04987463 | 2021–2026 | Infants with TSC | III | 60 (≤ 16 weeks) | Recruiting | Efficacy, tolerability, and safety in seizures and TSC-related tumor volume |
|  | NCT04595513 | 2020–2022 | Infants with TSC and epilepsy | I/II | 65 (≤ 6 months) | Recruiting | Epilepsy prevention |
|  | NCT01929642 | 2013–2016 | Patients with TSC and self-injury/autism | II | 3 (2–30 years) | Completed | Efficacy and safety in autism |
Everolimus | NCT01730209 | 2012–2016 | Patients with TSC and TSC Related Cognitive Disability/TSC Related Autism/TSC Related Learning Problems | II/III | 60 (4–15 years) | Unknown status | Efficacy and safety in autism and neuropsychological deficits |
|  | NCT00411619 | 2007–2014 | Patients with TSC and SEGA | I/II | 28 (≥ 3 years) | Completed | Efficacy and safety in SEGA volume |
|  | NCT01713946 (EXIST-3) | 2013–2017 | Patients with TSC-associated Refractory Seizures | III | 366 (2–65 years) | Completed | Efficacy and safety as adjunctive therapy in refractory partial-onset seizures |
|  | NCT01070316 | 2010–2016 | Patients with TSC and epilepsy | I/II | 20 (≥ 2 years) | Completed | Efficacy and safety in epilespy |
|  | NCT00789828 (EXIST-1) | 2009–2014 | Patients with TSC and SEGA | III | 117 (all ages) | Completed | Efficacy and safety in SEGA volume |
|  | NCT01954693 | 2012–2018 | Patients with TSC | II | 48 (16–60 years) | Unknown status | Efficacy and safety in neurocognitive problems |
|  | NCT02962414 | 2017–2027 | Patients with TSC | III | 206 (2–65 years) | Active, not recruiting | Long-term safety |
|  | NCT02451696 | 2014–2017 | Patients with TSC and epilepsy/focal cortical dysplasia | II | 15 (2–40 years) | Completed | Effects of everolimus on brain mTOR activity and cortical hyperexcitability |
|  | NCT01289912 | 2011–2014 | Patients with TSC | II | 52 (6–21 years) | Completed | Efficacy and safety in neurocognition |
Lung | Â | Â | Â | Â | Â | Â | Â |
Rapamycin | NCT02432560 | 2015–2021 | Patients with LAM | NA | 600 (≥ 18 years) | Active, not recruiting | Long term safety and efficacy in LAM |
|  | NCT03150914 | 2018–2023 | Patients with LAM | III | 60 (≥ 18 years) | Recruiting | Efficacy in FEV1, DLCO and TLC |
|  | NCT00414648 | 2006–2011 | Patients with LAM | III | 120 (≥ 18 years) | Unknown status | Safety and efficacy in LAM |
Everolimus | NCT01059318 | 2010–2012 | Patients with LAM | II | 24 (≥ 18 years) | Completed | Safety and efficacy in LAM and change of VEGF-D |
Kidney | Â | Â | Â | Â | Â | Â | Â |
Rapamycin | NCT00490789 | 2005–2009 | Patients with TSC and LAM | II | 14 (18–65 years) | Unknown | Efficacy and safety in renal AML volume and FEV1 |
|  | NCT01217125 | 2008–2011 | Patients with TSC and renal AML | IV | 18 (≥ 10 years) | Completed | Efficacy and safety in renal AML volume |
Everolimus | NCT00457964 | 2005–2013 | Patients with TSC and LAM | I/II | 36 (18–65 years) | Completed | Efficacy and safety in renal AML volume and FEV1 |
|  | NCT00790400 (EXIST-2) | 2009–2015 | Patients with TSC and LAM | III | 118 (≥ 18 years) | Completed | Efficacy and safety in renal AML volume and FEV1 |
|  | NCT03525834 | 2018–2020 | Patients with TSC and renal AML | IV | 40 (≥ 18 years) | Completed | Efficacy and safety in renal AML volume |
Skin | Â | Â | Â | Â | Â | Â | Â |
Rapamycin | NCT03363763 | 2017–2022 | Patients with TSC and facial angiofibromas | II | 45 (2–21 years) | Recruiting | Safety and efficacy in cutaneous angiofibromas |
|  | NCT03826628 | 2019–2021 | Patients with TSC and facial angiofibromas | II/III | 120 (6–65 years) | Recruiting | Safety and efficacy in facial angiofibroma |
|  | NCT02634931 | 2015–2018 | Tuberous Sclerosis Patients with TSC and skin lesions (angiofibroma, hypomelanotic macule or plaque) | III | 94 (≥ 3 years) | Completed | Safety and efficacy in angiofibroma |
|  | NCT01031901 | 2009–2011 | Patients with TSC/NF1 and fibromatous lesions (angiofibromas or neurofibromas) | I | 52 (≥ 13 years) | Completed | Safety in cutaneous fibromatous lesions |
|  | NCT02635789 | 2015–2016 | Tuberous Sclerosis Patients with TSC and skin lesions (angiofibroma, hypomelanotic macule or plaque) | III | 62 (≥ 3 years) | Completed | Safety and efficacy in angiofibroma and other skin lesions |
|  | NCT03140449 | 2013–2016 | Patients with TSC and facial angiofibromas | III | 52 (7–65 years) | Completed | Safety and efficacy in angiofibroma |
|  | NCT01853423 | 2013–2016 | Patients with TSC and facial angiofibromas | I | 11 (3–45 years) | Completed | Efficacy, tolerability, and safety in facial angiofibroma |
|  | NCT01526356 | 2012–2014 | Patients with TSC and angiofibromas | II | 179 (all ages) | Completed | Safety and efficacy in cutaneous angiofibromas |