NCT03764215: Tasigna HD

Nilotinib in Huntington's Disease

Status unknown Phase 1 Last updated 20 February 2020

What this trial tests

Phase 1 trial testing Nilotinib 150 MG in Huntington Disease in 10 participants. Status unknown.

Timeline

15 November 2018

Primary endpoint
30 November 2020

30 November 2020

Quick facts

Lead sponsor	Georgetown University
Phase	Phase 1
Status	Status unknown
Study type	INTERVENTIONAL
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	15 November 2018
Primary completion	30 November 2020
Estimated completion	30 November 2020
Sites	1 location across United States

Drugs / interventions tested

• Nilotinib 150 MG — full drug profile →

Conditions studied

• Huntington Disease — all drugs for Huntington Disease →

Sponsor

Georgetown University

Who can join

Adults 25 to 90, any sex, with Huntington Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Based on strong pre-clinical evidence of the effects of Nilotinib on neurodegenerative pathologies, including autophagic clearance of neurotoxic proteins, neurotransmitters (dopamine and glutamate), immunity and behavior, the investigators conducted an open label pilot clinical trial in mid-to-advanced PD with dementia (PDD) and Dementia with Lewy Bodies (DLB) (stage 3-4) patients. Participants (N=12) were randomized 1:1 to once daily oral dose of 150mg and 300mg Nilotinib for 6 months. The investigators data suggests that Nilotinib penetrates the brain and inhibits CSF Abelson (Abl) activity via reduction of phosphorylated Abl in agreement with pre-clinical data. Several studies suggest that CSF alpha-Synuclein and Abeta42 are decreased and CSF total Tau and p-Tau are increased in PD and DLB. The investigators data shows attenuation of loss of CSF alpha-Synuclein and Abeta40/42 with 300mg (50% of the CML dose) compared to 150mg Nilotinib after 6 months treatment. CSF homovanillic acid (HVA), which is a by-product of dopamine metabolism, is significantly increased; and CSF total Tau and p-Tau are significantly reduced (N=5, P\<0.05) with 300mg Nilotinib between baseline and 6 months treatment. Despite the reduction of L-Dopa replacement therapies in our study, the Unified Parkinson's Disease Rating Scale (UDPRS) I-IV scores improved with 150mg (3.5 points) and 300mg (11 points) from baseline to 6 months and worsened (13.7 points and 11.4 points) after 3 months withdrawal of 150mg and 300mg, respectively. Other non-motor functions e.g. constipation was resolved in all patients and cognition was also improved (3.5 points) using both the Mini-Mental Status Exam (MMSE) or the Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) between baseline and 6 months. MMSE scores returned to baseline after 3 months of Nilotinib withdrawal. These data are very compelling to evaluate the effects of Nilotinib in an open label proof-of-concept study in patients with HD.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. New Avenues for the Treatment of Huntington's Disease.
   Kim A, Lalonde K, Truesdell A, Gomes Welter P, et al · · 2021 · cited 130× · PMID 34445070 · DOI 10.3390/ijms22168363
2. From Pathogenesis to Therapeutics: A Review of 150 Years of Huntington's Disease Research.
   Jiang A, Handley RR, Lehnert K, Snell RG. · · 2023 · cited 88× · PMID 37629202 · DOI 10.3390/ijms241613021
3. Current and Possible Future Therapeutic Options for Huntington's Disease.
   Ferguson MW, Kennedy CJ, Palpagama TH, Waldvogel HJ, et al · · 2022 · cited 66× · PMID 35615642 · DOI 10.1177/11795735221092517
4. Therapeutic Update on Huntington's Disease: Symptomatic Treatments and Emerging Disease-Modifying Therapies.
   Dash D, Mestre TA. · · 2020 · cited 35× · PMID 32705582 · DOI 10.1007/s13311-020-00891-w
5. Autophagy-Lysosomal Pathway as Potential Therapeutic Target in Parkinson's Disease.
   Bonam SR, Tranchant C, Muller S. · · 2021 · cited 34× · PMID 34944054 · DOI 10.3390/cells10123547
6. Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders.
   Shah S, Dooms MM, Amaral-Garcia S, Igoillo-Esteve M. · · 2021 · cited 32× · PMID 34992533 · DOI 10.3389/fphar.2021.768023
7. Huntington's Disease Clinical Trials Corner: March 2024.
   Estevez-Fraga C, Tabrizi SJ, Wild EJ. · · 2024 · cited 31× · PMID 38489195 · DOI 10.3233/jhd-240017
8. Emerging Role of NLRP3 Inflammasome/Pyroptosis in Huntington's Disease.
   Paldino E, Fusco FR. · · 2022 · cited 25× · PMID 35955494 · DOI 10.3390/ijms23158363