OLE phase 1b/2a study of WVE-120102 in Huntington's Disease
Research type
Research Study
Full title
A Multicenter, Open-label Extension (OLE) Study to Evaluate the Safety,Pharmacodynamics,and Clinical Effects of WVE-120102 in Patients with Huntington’s Disease
IRAS ID
269307
Contact name
Timothy Harrower
Contact email
Sponsor organisation
WAVE Life Sciences Ltd
Eudract number
2019-002178-30
Duration of Study in the UK
2 years, 5 months, 1 days
Research summary
Research Summary
There is no cure for HD and it is invariably fatal. Some symptoms can be managed with existing medications, but none of these medicines can slow or reverse the disease. HD is caused by known mutations on a single gene, called the Huntingtin gene. All people carry the Huntingtin gene, which makes Huntingtin protein that is important for normal brain development.
The mutation on the HTT gene in people with HD leads to production of another type of protein known as the mutant Huntingtin (mHTT) protein. Study drug WVE-120102 is designed to selectively reduce mHTT protein while leaving normal Huntington protein intact.
Research suggests that selectively lowering mHTT protein has the potential to slow the progression of HD. This is an open label extension of the first clinical study conducted with WVE-120102. The purpose of this OLE is to test the safety, tolerability and clinical effects of WVE-120102 in patients with early HD.
70 eligible patients who completed the WVE-HDSNP2-001 study will be enrolled into 1 of 3 dose groups (4, 8 and 16 mg) dependent on dose received in WVE-HDSNP2-001 study. WVE-120102 will be administered every 4 weeks for up to 97 weeks. The patients will be monitored for safety every 4 weeks and at week 101. As results from WVE-HDSNP2-001 become available the dose may change if higher doses are found to be acceptable.
Study procedures will include analysis of blood, urine, and spinal fluid, vital signs, ECGs, physical exams, MRI, and HD clinical assessments.Summary of Results
PD and MRI Results:
Patients received up to 12 months of once monthly WVE-120102 in this study. Following monthly treatment, there were no apparent trends in terms of target engagement, as measured by changes in PD biomarkers of mHTT, total huntingtin protein (tHTT), wild-type huntingtin protein (wtHTT), or NfL and analysis of MRI parameters.Clinical Effects:
Following monthly treatment, there were no apparent trends in measurements of clinical effects, including the UHDRS and PBA-s.PK results:
WVE-120102 was present in the CSF of patients enrolled at both the 4, 8, and 16 mg dose groups after monthly IT administration. There were variable results but no overall trend and no apparent accumulation in the CSF.Safety results:
Of the 39 patients enrolled in this study, 36 received at least 1 dose of WVE-120102. The percentage of patients who experienced a TEAE was generally similar across the WVE-120102 dose levels administered. There was an apparent dose-related trend in regards to incidence of SAEs and severe TEAEs.Overall there were 9 patients (25.0%) who experienced an SAE; these were amnesia, confusional state, meningitis, and meningitis aseptic (experienced by 2 patients each), aggression, agitation, nervous system disorder, and pyrexia (1 patient each).
There were no deaths during the study and no TEAEs within the HLGT Spinal cord and nerve root disorders.
WVE-120102 was not associated with any dose-related changes in clinical chemistry, hematology, coagulation, or urinalysis parameters. WVE-120102 was also not associated with any changes in CSF safety laboratory assessments. In addition, no dose-related trends were observed in vital signs, ECGs, or Columbia Suicide Severity Rating Scale (C-SSRS).Conclusion:
Based on the efficacy findings in this study at the time of the interim analysis, the Sponsor decided to terminate the study as the benefit/risk analysis did not warrant continued dose escalation.REC name
London - West London & GTAC Research Ethics Committee
REC reference
19/LO/1377
Date of REC Opinion
11 Nov 2019
REC opinion
Further Information Favourable Opinion