Study of SOM0226 in familial amyloid polyneuropathy (FAP) patients and asymptomatic carriers to evaluate protein stabilization activity

• Register: EUCTR
• Last refreshed on: 7 December 2015
• Main ID: EUCTR2014-001586-27-ES
• Date of registration: 02/06/2014
• Prospective Registration: Yes
• Primary sponsor: SOM Innovation Biotech SL (SOM Biotech)
• Public title: Study of SOM0226 in familial amyloid polyneuropathy (FAP) patients and asymptomatic carriers to evaluate protein stabilization activity
• Scientific title: Study of SOM0226 in familial amyloid polyneuropathy (FAP) patients and asymptomatic carriers to evaluate protein stabilization activity
• Date of first enrolment: 25/07/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001586-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Spain

Contacts

• Name: Miriam García Diez
• Affiliation: ARO-VHIR

• Name: Miriam García Diez
• Affiliation: ARO-VHIR

Key inclusion & exclusion criteria

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 time of consent.
- Two cohorts defined by TTR variant:
Wild type TTR: healthy patients
V30M TTR mutant: Asymptomatic carriers with documented
mutation V30M 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
The participant may not enter the study if ANY of the following apply:
- Female participants 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.
- Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant?s ability to participate in 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 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with familial amyloid polyneuropathy (FAP), asymptomatic carriers and healthy volunteers
MedDRA version: 17.0 Level: LLT Classification code 10057949 Term: Familial amyloid polyneuropathy System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Tasmar
Pharmaceutical Form: Coated tablet
INN or Proposed INN: TOLCAPONE
CAS Number: 134308-13-7
Current Sponsor code: SOM0226
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: Determine whether SOM0226 induces TTR stabilization by evaluating whether treatment with SOM0226 prevents urea-induced denaturation of tetrameric TTR.

Timepoint(s) of evaluation of this end point: Phase A (24 hours) and Phase B (32 hours). Between these two phases there is a washout period of 6 weeks (+-2 weeks)

Primary end point(s): 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.

TTR stabilization will be measured in plasma samples obtained from each participant before first dose and at different times during each treatment period. In terms of assessing efficacy, a positive result will be a TTR stabilization value superior to 20%.

Secondary Objective: - The secondary objective is to determine the plasma concentration of SOM0226 needed to induce a maximal stabilization of TTR in healthy volunteers, patients and asymptomatic carriers.
- A pharmacodynamics assessment will be used to determine an effective dose of SOM0226 to confer TTR stabilization, by determining the molar ratio SOM0226:TTR that must be reached in plasma to induce maximal stabilization of TTR in healthy individuals, patients and asymptomatic carriers.

Secondary Outcome(s)

Secondary end point(s): - The pharmacodynamics characteristics of SOM0226 will be assessed to determine which plasma SOM0226:TTR molar ratio is needed to reach a plateau of TTR stabilization.
- The concentration of SOM0226 will be determined in all
plasma samples obtained at different times during each
treatment period.
- The concentration of TTR will be determined in all
plasma samples, and the molar ratio SOM0226:TTR in
each sample will be calculated.
- Safety will be assessed by ALT and AST liver function measures in samples obtained at the end of each treatment phase (24 hours in Phase A and 32 hours in Phase B).

Timepoint(s) of evaluation of this end point: Phase A (24 hours) and Phase B (32 hours). Between these two phases there is a washout period of 6 weeks (+-2 weeks)

Secondary ID(s)

SOMCT01-C

Source(s) of Monetary Support

Fundació Vall d'Hebron-Institut de Recerca