A Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies

Browse trials for

• Lewy Body Disease 229
• Dementia 2,166

Keywords

• Dementia
• France
• neflamapimod

Study arms

• Experimental
  Neflamapimod, Open-label

  Neflamapimod will be administered orally, with food, for 24 weeks in subjects with DLB. Subjects will receive 4 capsules per day (80 mg BID), two capsules in the morning and two capsules in the evening, with food (i.e., with the morning and evening meals)

  Drug: neflamapimod

Interventions

• Drugneflamapimod

  Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase 14 (p38α). It is administered orally in 40 mg capsules.

  Also known as: VX-745

Primary outcomes

1. Evaluate the safety and tolerability 80 mg neflamapimod given twice daily in patients with dementia with Lewy bodies.

   The safety and tolerability of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via the incidence of treatment-emergent Adverse events (AEs) and Serious adverse events (SAEs) during 24 weeks of treatment

   Time frame: From enrollment until the end of treatment at 24 weeks

2. Evaluate the safety and tolerability of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.

   The safety and tolerability of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via the incidence of elevations in amino-alanine transferase (ALT) and/or aspartate amino-transferase (AST) ≥ three times the upper limit of normal during 24 weeks of treatment

   Time frame: From enrollment until the end of treatment at 24 weeks

3. Evaluate the maximum plasma concentration (Cmax) of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.

   The maximum plasma concentration (Cmax) of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via mean (with 95% confidence interval) plasma drug concentration at steady state during 24 weeks of treatment with neflamapimod 80mg BID.

   Time frame: From enrollment until the end of treatment at 24 weeks

4. Evaluate the trough plasma concentration (Ctrough) of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.

   The trough plasma concentration (Ctrough) of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via mean (with 95% confidence interval) plasma drug concentration at steady state during 24 weeks of treatment with neflamapimod 80mg BID.

   Time frame: From enrollment until the end of treatment at 24 weeks

Secondary outcomes

1. Change in ADNI-EF composite score from baseline to 24 weeks

   Effects of neflamapimod treatment will be assessed via changes in the mean composite score for Alzheimer's Disease Neuroimaging Initiative Executive Functioning composite scale (ADNI-EF) from baseline to 24 weeks where composite scores range from -3.0 to 3.0 and a positive change in composite score indicates improvement in cognition and a negative change in composite score indicates a worsening in cognition.

   Time frame: From enrollment until the end of treatment at 24 weeks

2. Change in CDR-SB score from baseline to 24 weeks

   Effects of neflamapimod treatment will be assessed via changes in the Clinical Dementia Rating Sum of Boxes (CDR-SB) score from baseline to 24 weeks. CDR-SB scores range from 0 to 18 with a higher score indicating worsening of cognitive impairment.

   Time frame: From enrollment until the end of treatment at 24 weeks

3. Change in TUG test results from baseline to 24 weeks

   Effects of neflamapimod treatment will be assessed via changes in Timed Up and Go (TUG) test results from baseline to 24 weeks. TUG scores typically range from 6 to 20 seconds with a lower score indicating better mobility and a higher score indicating worse mobility.

   Time frame: From enrollment until the end of treatment at 24 weeks

Other outcomes

1. Change in MBI-C score from baseline to 24 weeks

   Effects of neflamapimod treatment will be assessed via changes in the Mild Behavioral Impairment Checklist (MBI-C) scale from baseline to 24 weeks. The scale ranges from 0 to 102, with lower scores indicating less severe symptoms and higher scores indicating more severe symptoms.

   Time frame: From enrollment until the end of treatment at 24 weeks

2. Changes in DCFS from baseline to 24 weeks

   Effects of neflamapimod treatment will be assessed via changes in the Dementia Cognitive Fluctuations Scale (DCFS) score from baseline to 24 weeks. DCFS scores range from 4 to 20 where a higher score indicates more severe cognitive fluctuations and disease worsening.

   Time frame: From enrollment until the end of treatment at 24 weeks

3. Changes hallucinations (PDAP questionnaire) from baseline to 24 weeks

   Effects of neflamapimod treatment will be assessed via changes in hallucinations as measured by the Parkinson's disease-associated psychotic symptoms questionnaire (PDAP) score from baseline to 24 weeks where a higher score indicates more severe symptoms. The scores range from 0 to 9 for patient responses and 0 to 9 for caregiver responses where a lower score indicates improvement and a higher score indicates worsening in condition.

   Time frame: From enrollment until the end of treatment at 24 weeks

4. Changes in NBM volume from baseline to 16 weeks

   Effects of neflamapimod treatment will be assessed via changes in volume of nucleus basalis of Meynert (NBM) as measured by structural Magnetic Resonance Imaging (MRI) from baseline to 16 weeks where a reduction in volume indicates degeneration.

   Time frame: From enrollment until 16 weeks

Individual participant data

Plan to share: No