Study of SOM0226 in Familial Amyloid Polyneuropathy

Study of SOM0226 in Familial Amyloid Polyneuropathy (FAP) Patients and Asymptomatic Carriers to Evaluate Protein Stabilization Activity

Clinical proof of concept study to evaluate SOM0226 efficacy in TTR Amyloidosis.

Study Overview

• Status: Completed
• Conditions: Familial Amyloid Polyneuropathy (FAP)
• Intervention / Treatment: Drug: SOM0226

Detailed Description

This is an open label interventional Phase IIa proof of concept clinical trial designed in two phases separated by a washout period of 6 weeks (± 2 weeks) , to evaluate the TTR stabilization activity of SOM0226 in healthy volunteers (wild type), TTR-FAP patients and asymptomatic carriers.

• Phase A (24 hours): SOM0226 single dose
• Phase B (32 hours): SOM0226 multiple dose

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Vall d'Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the study
• Male or Female, aged 18 years or above at the time of consent
• Two cohorts defined by TTR variant (wild type: healthy volunteers; TTR mutant: asymptomatic carriers with documented mutation in TTR or diagnosed TTR-FAP patients (stage 1 or 2) not undergoing pharmacological treatment with Vyndaqel
• Body Mass Index (BMI) > 17.5 kg/m2
• Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 2 month thereafter
• Able (in the Investigators opinion) and willing to comply with all study requirements

Exclusion Criteria:

• Female participant who is pregnant, lactating or planning pregnancy during the course of the study
• Evidence of history of clinically significant hepatic disease
• An ALT or AST measurement > 2 times the ULN (Upper Limit of Normal)
• Scheduled elective surgery or other procedures requiring general anaesthesia during the study
• Donation of blood during the study or within the past 4 weeks
• Treatment (during the study or within the past 4 weeks) with a prescription or investigational drug for the treatment of TTR amyloidosis
• Treatment with NSAIDs (nonsteroidal antiinflammatory drug) during the study or within the past 4 weeks. The following NSAID are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethacin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam and sulindac

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOM0226 single dose	Drug: SOM0226; Oral
Experimental: SOM0226 multiple doses	Drug: SOM0226; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTR stabilization	TTR stabilization will be measured by determining the concentration of tetrameric TTR after denaturation. The ratio of TTR tetramer after denaturation / TTR tetramer before denaturation of plasma samples from treated subjects will be compared to their baseline ratio. TTR stabilization will be determined as percentage of the baseline ratio.	24 hours and 32 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics assessment	Determine the minimal molar ratio SOM0226:TTR that must be reached in plasma to confer maximal TTR stabilization	24 hours and 32 hours
Safety	Drug safety will be assessed by blood biochemistry and hematology analysis, patient exploration and adverse event reporting	24 hours

Collaborators and Investigators

• Sponsor: SOM Innovation Biotech SA
• Collaborators: Hospital Vall d'Hebron
• Investigators: Principal Investigator: Josep Gámez, MD, Hospital Vall d'Hebron

Publications and helpful links

General Publications

• Gamez J, Salvado M, Reig N, Sune P, Casasnovas C, Rojas-Garcia R, Insa R. Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study. Amyloid. 2019 Jun;26(2):74-84. doi: 10.1080/13506129.2019.1597702. Epub 2019 May 23.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: July 9, 2014
• First Submitted That Met QC Criteria: July 14, 2014
• First Posted (Estimate): July 16, 2014

Study Record Updates

• Last Update Posted (Estimate): November 30, 2016
• Last Update Submitted That Met QC Criteria: November 29, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: TTR; Amyloidosis; Transthyretin; SOM0226; Familiar Amyloid Polyneuropathy
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Proteostasis Deficiencies; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Amyloidosis, Familial; Amyloidosis; Polyneuropathies; Amyloid Neuropathies; Amyloid Neuropathies, Familial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Tolcapone
• Other Study ID Numbers: SOMCT01-C; 2014-001586-27 (EudraCT Number)