Trial Outcomes & Findings for Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A (NCT NCT01401257)

Results Overview

The Primary Objective is to assess the clinical and laboratory safety and tolerability of three doses of PXT3003 administered orally for 12 months to CMT1A patients versus placebo. Number of participants with adverse events in each arm.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Screening, randomization, 1-, 3-, 6-, 9-, 12-month treatment and 1-month follow-up

Results posted on

2017-11-22

Participant Flow

Participant milestones

Participant milestones
Measure	PXT3003 Low Dose Oral Liquid formulation, 1/100, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 Intermediate Dose Oral Liquid formulation, 1/50, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 High Dose Oral Liquid formulation, 1/10, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	Placebo Oral Liquid formulation, bid, 12 months Placebo: Liquid,5 ml, twice a day, 12-month treatment
Overall Study STARTED	21	21	19	19
Overall Study COMPLETED	21	19	16	17
Overall Study NOT COMPLETED	0	2	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PXT3003 Low Dose n=21 Participants Oral Liquid formulation, 1/100, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 Intermediate Dose n=21 Participants Oral Liquid formulation, 1/50, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 High Dose n=19 Participants Oral Liquid formulation, 1/10, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	Placebo n=19 Participants Oral Liquid formulation, bid, 12 months Placebo: Liquid,5 ml, twice a day, 12-month treatment	Total n=80 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=5 Participants	21 Participants n=7 Participants	19 Participants n=5 Participants	19 Participants n=4 Participants	80 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	47.9 years n=5 Participants	44.3 years n=7 Participants	44.6 years n=5 Participants	43.2 years n=4 Participants	45.1 years n=21 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	13 Participants n=7 Participants	10 Participants n=5 Participants	11 Participants n=4 Participants	48 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	32 Participants n=21 Participants
Region of Enrollment France	21 participants n=5 Participants	21 participants n=7 Participants	19 participants n=5 Participants	19 participants n=4 Participants	80 participants n=21 Participants

PRIMARY outcome

Timeframe: Screening, randomization, 1-, 3-, 6-, 9-, 12-month treatment and 1-month follow-up

The Primary Objective is to assess the clinical and laboratory safety and tolerability of three doses of PXT3003 administered orally for 12 months to CMT1A patients versus placebo. Number of participants with adverse events in each arm.

Outcome measures

Outcome measures
Measure	PXT3003 Low Dose n=21 Participants Oral Liquid formulation, 1/100, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 Intermediate Dose n=21 Participants Oral Liquid formulation, 1/50, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 High Dose n=19 Participants Oral Liquid formulation, 1/10, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	Placebo n=19 Participants Oral Liquid formulation, bid, 12 months Placebo: Liquid,5 ml, twice a day, 12-month treatment
Safety and Tolerability of PXT3003	21 Participants	21 Participants	19 Participants	19 Participants

SECONDARY outcome

Timeframe: Screening, randomization, 3-, 6-, 9- and 12-months treatment

Efficacy scores and functional tests will be assessed CMTNS/CMTES:ONLS, VAS, fatigue, pain, six minute walk test (6MWT), nine-hole peg test, quantified muscular testing (QMT; hand grip and foot dorsiflexion), CGI. For each test or score, change from baseline after 3-,6-, 9- and 12-months of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization and 12-month treatment

A cutaneous biopsy (consisting in 2 small punch biopsies) will be performed to assess PMP22 mRNA expression and intra-epidermal axon density. Change from baseline after 12-month of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening, randomization, 3-, 6-, 9- and 12-month treatment

Electrophysiological examination will be performed to assess sensory and motor responses of the median and ulnar nerves (non-dominant side) including: NCV, compound muscle action potential (CMAP) and SNAP. Change from baseline after 3-,6-, 9- and 12-months of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization and 3-month treatment

Dosages of biochemical biomarkers in plasma. Change from baseline after 3-month of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization, 1-, 6- and 12-month treatment

PXT3003 plasmatic concentrations after one administration (randomization) and after 1-,6-and 12-months of treatment.

Outcome measures

Outcome data not reported

Adverse Events

PXT3003 Low Dose

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

PXT3003 Intermediate Dose

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

PXT3003 High Dose

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PXT3003 Low Dose n=21 participants at risk Oral Liquid formulation, 1/100, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 Intermediate Dose n=21 participants at risk Oral Liquid formulation, 1/50, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 High Dose n=19 participants at risk Oral Liquid formulation, 1/10, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	Placebo n=19 participants at risk Oral Liquid formulation, bid, 12 months Placebo: Liquid,5 ml, twice a day, 12-month treatment
Musculoskeletal and connective tissue disorders osteoarthritis	4.8% 1/21 • 13 months	0.00% 0/21 • 13 months	0.00% 0/19 • 13 months	0.00% 0/19 • 13 months
Gastrointestinal disorders Hemorrhoids	4.8% 1/21 • 13 months	0.00% 0/21 • 13 months	0.00% 0/19 • 13 months	0.00% 0/19 • 13 months

Other adverse events

Other adverse events
Measure	PXT3003 Low Dose n=21 participants at risk Oral Liquid formulation, 1/100, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 Intermediate Dose n=21 participants at risk Oral Liquid formulation, 1/50, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	PXT3003 High Dose n=19 participants at risk Oral Liquid formulation, 1/10, bid, 12 months PXT3003: Liquid,5 ml, twice a day, 12-month treatment	Placebo n=19 participants at risk Oral Liquid formulation, bid, 12 months Placebo: Liquid,5 ml, twice a day, 12-month treatment
Infections and infestations Infections and infestations	52.4% 11/21 • 13 months	47.6% 10/21 • 13 months	57.9% 11/19 • 13 months	42.1% 8/19 • 13 months
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	57.1% 12/21 • 13 months	38.1% 8/21 • 13 months	68.4% 13/19 • 13 months	36.8% 7/19 • 13 months
Nervous system disorders Nervous system disorders	38.1% 8/21 • 13 months	38.1% 8/21 • 13 months	57.9% 11/19 • 13 months	47.4% 9/19 • 13 months
Gastrointestinal disorders Gastrointestinal disorders	33.3% 7/21 • 13 months	23.8% 5/21 • 13 months	52.6% 10/19 • 13 months	57.9% 11/19 • 13 months

Additional Information

Pr Shahram ATTARIAN

Hôpital La Timone, Marseille

Phone: 04 91 38 65

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No individual publication (paper, abstract, poster, oral presentation) is allowed until results of the complete study have been published. The Investigator agrees that any proposed publication, presentation or use of results arising from the Investigation will be submitted to Pharnext for review and written agreement prior to submission.
Publication restrictions are in place

Restriction type: OTHER