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Clinical Trial Results:
A randomized, double-blind, placebo controlled, parallel group, multicentric, phase IIa clinical trial to evaluate the safety, tolerability and therapeutic efficacy of daily oral treatment with NFX88 on neuropathic pain in patients with spinal cord injury.

Summary
EudraCT number	2018-004792-13
Trial protocol	ES
Global end of trial date	12 Apr 2022

Results information
Results version number	v1(current)
This version publication date	20 May 2023
First version publication date	20 May 2023
Other versions
Summary report(s)	Protocol Synopsis

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

NFX88-2A-2018

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Neurofixpharma

Sponsor organisation address

Calle del Adaja, 3 Parque Científico de la Universidad de Salamanca Edificio M3 PB05 Sala 1, Salamanca, Spain, 37185

Public contact

Miguel Angel Ávila Santiago, Neurofixpharma S.A., 0034 674052566, miguelangel.avila@neurofixpharma.com

Scientific contact

Miguel Angel Ávila Santiago, Neurofixpharma S.A., 0034 674052566, miguelangel.avila@neurofixpharma.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Nov 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

12 Apr 2022

Global end of trial reached?

Yes

Global end of trial date

12 Apr 2022

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to assess the safety and tolerability of NFX88 in spinal cord injury patients with neuropathic pain over ninety-day treatment period.

Protection of trial subjects

Treated in routine care

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Jun 2019

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

1 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 61

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Recruitment phase: ~18 months 60 patients to be recruited in 4 arms

Screening details

Patients should undergo a baseline visit within 7 days prior to their study randomisation. The Principal Investigator or his/her designee will obtain written informed consent before any study related procedures are performed.

Number of subjects started

Number of subjects completed

Period 1 title

Randomization (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

Due to the objectives of the study, the identity of placebo and NFX88 treatment will both be blinded. Patients will be randomised to receive any of them in a double-blind model such that neither the investigator nor the patient will know which combination is being administered.

Are arms mutually exclusive

Yes

ARM 1: 1.05 g/day

Arm description

1.05 g/day NFX88

Arm type

Experimental

Investigational medicinal product name

NFX88

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1.05 g/day oral use

ARM 2. 2.1g/day NFX88

Arm description

2.10 g/day NFX88

Arm type

Active comparator

Investigational medicinal product name

NFX88

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2.10 g/day ORAL USE

ARM 3: 4.2 g/day

Arm description

4.20 g/day NFX8

Arm type

Active comparator

Investigational medicinal product name

NFX88

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4.20 g/day ORAL USE

ARM 4: 0.0 g/day

Arm description

PLACEBO

Arm type

Placebo

Investigational medicinal product name

PLACEBO

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ORAL USE

Number of subjects in period 1	ARM 1: 1.05 g/day	ARM 2. 2.1g/day NFX88	ARM 3: 4.2 g/day	ARM 4: 0.0 g/day
Started	15	15	16	15
Completed	12	11	12	9
Not completed	3	4	4	6
Consent withdrawn by subject	1	-	1	1
Physician decision	-	2	-	-
Adverse event, non-fatal	1	1	2	1
Lost to follow-up	1	-	-	-
Protocol deviation	-	1	1	4

Baseline characteristics

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Reporting group title

Randomization

Reporting group description

Reporting group values	Randomization	Total
Number of subjects	61	61
Age categorical
Units: Subjects
In utero		0
Preterm newborn infants (gestational age < 37 wks)		0
Newborns (0-27 days)		0
Infants and toddlers (28 days-23 months)		0
Children (2-11 years)		0
Adolescents (12-17 years)		0
Adults (18-64 years)		0
From 65-84 years		0
85 years and over		0
Age continuous
Male or Female 18 to 65 years of age
Units: years
arithmetic mean (full range (min-max))	47.2 (22 to 67)	-
Gender categorical
Male or Female 18 to 65 years of age
Units: Subjects
Female	12	12
Male	49	49

End points

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Reporting group title

ARM 1: 1.05 g/day

Reporting group description

1.05 g/day NFX88

Reporting group title

ARM 2. 2.1g/day NFX88

Reporting group description

2.10 g/day NFX88

Reporting group title

ARM 3: 4.2 g/day

Reporting group description

4.20 g/day NFX8

Reporting group title

ARM 4: 0.0 g/day

Reporting group description

PLACEBO

Primary: Safety and tolerability of NFX88 administered by 90 days

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End point title

Safety and tolerability of NFX88 administered by 90 days

End point description

Safety and tolerability of NFX88 administered for ninety days will be evaluated by assessing the number, severity, and type of Adverse Event, including changes in vital signs, safety laboratory values (haematology, clinical chemistry and urinalysis), ECGs, and MAS (Modified Ashworth Scale) (e.g. to monitor spasticity worsening) and ASIA (e.g. to monitor neurological worsening) scores. Non-worsening of spasticity and motor score will be obtaining as the non-increase of the scales values MAS and ASIA, respectively, from the beginning to the end of the treatment.

End point type

Primary

End point timeframe

Safety and tolerability of NFX88 administered for 3 months will be assessed by the number, severity, and type of Adverse Events from screening visit (-7 days) to the Follow up visit (120 days after the start of the treatment)

End point values	ARM 1: 1.05 g/day	ARM 2. 2.1g/day NFX88	ARM 3: 4.2 g/day	ARM 4: 0.0 g/day
Number of subjects analysed	15	15	16	15
Units: Adverse Events
Severe	1	2	3	1
Mild	14	4	18	14
Moderate	1	0	3	1

Safety analysis

Statistical analysis description

CODING: For the analysis, each adverse event (AE) was coded as a binary variable (Present/Absent) in each study subject. AEs defined as “unsafe levels” of some lab parameter or clinical outcome (vital signs, ECGs, ASIA and MAS scales) were also coded as binary. If the same AE occur at different degrees of severity several binary variables were calculated

Comparison groups

ARM 1: 1.05 g/day v ARM 2. 2.1g/day NFX88 v ARM 3: 4.2 g/day v ARM 4: 0.0 g/day

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

≤ 0.05

Method

Fisher exact

Confidence interval

Notes
[1] - Tables with counts and proportions of each AE in each arm were compiled. For the intervention arms, exact confidence intervals for the proportion of each AE were estimated. Comparison of the risk of each EA between arms was done with Fisher’s exact tests. To increase power, the patients from the three intervention doses were analyzed together in one intervention arm. If some AE turned out to be relatively common, a logistic regression model was built to examine if there is a dose-response ef

Adverse events

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Timeframe for reporting adverse events

Safety and tolerability of NFX88 administered for 90 days was assessed in the different visits: Since SV (- 7days) to Follow-up visit (120 days after the beginning of the treatment)

Adverse event reporting additional description

Safety and tolerability of NFX88 administered for 3 months will be assessed by the number, severity, and type of Adverse Events, including changes in: - Vital signs. - ECG. - Clinical laboratory parameters - Spasticity score as determined by MAS -Sensory and motor function by ASIA scale

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

ARM 1: 1.05 g/day

Reporting group description

1.05 g/day NFX88

Reporting group title

ARM 2. 2.1g/day NFX88

Reporting group description

2.10 g/day NFX88

Reporting group title

ARM 3: 4.2 g/day

Reporting group description

4.20 g/day NFX8

Reporting group title

ARM 4: 0.0 g/day

Reporting group description

PLACEBO

Serious adverse events	ARM 1: 1.05 g/day	ARM 2. 2.1g/day NFX88	ARM 3: 4.2 g/day	ARM 4: 0.0 g/day
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 15 (6.67%)	2 / 15 (13.33%)	1 / 16 (6.25%)	1 / 15 (6.67%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Vascular disorders
Vascular insufficiency
subjects affected / exposed	0 / 15 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
subjects affected / exposed	0 / 15 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Sepsis
subjects affected / exposed	0 / 15 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 15 (6.67%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	ARM 1: 1.05 g/day	ARM 2. 2.1g/day NFX88	ARM 3: 4.2 g/day	ARM 4: 0.0 g/day
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 15 (13.33%)	1 / 15 (6.67%)	4 / 16 (25.00%)	4 / 15 (26.67%)
Gastrointestinal disorders
Gastrointestinal disorder
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	1 / 16 (6.25%)	1 / 15 (6.67%)
occurrences all number	1	0	1	3
Renal and urinary disorders
Infection
subjects affected / exposed	1 / 15 (6.67%)	1 / 15 (6.67%)	3 / 16 (18.75%)	3 / 15 (20.00%)
occurrences all number	1	1	3	5

More information

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Were there any global substantial amendments to the protocol? Yes

23 May 2019

Initial protocol v1.0 dated 28dec2018 – Conditional approval obtained on 23May2019. New version of IMPD had to be submitted and approved before study start.

29 Apr 2020

Protocol v2.0 dated 13Mar2020 relevant amendment to increase the recruitment period, increase age inclusion criteria, clarify traumatic spinal cord injury meaning and specify more clearly the washout period for opioids and cannabinoids. Approved on 29Apr2020

18 Nov 2020

Protocol v3.0 dated 25Sep2020 relevant amendment to include the option for home visit due to COVID pandemic. Approved on 18Nov2020

20 Mar 2021

Protocol v4.0 dated 22Feb2021 relevant amendment to decrease the total number of patients to be included in the trial to 48. Approved on 20Mar2021

27 Oct 2021

Protocol v5.0 dated 09Sep2021 relevant amendment to decrease the total number of patients to be included in the trial to 44. Approved on 27Oct2021

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The recruitment and following up o the patients was slower and more complicated than usual due to the COVID pandemic situation during the years this study was carried on.

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Clinical trials

Clinical Trial Results:
A randomized, double-blind, placebo controlled, parallel group, multicentric, phase IIa clinical trial to evaluate the safety, tolerability and therapeutic efficacy of daily oral treatment with NFX88 on neuropathic pain in patients with spinal cord injury.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Safety and tolerability of NFX88 administered by 90 days

Primary: Safety and tolerability of NFX88 administered by 90 days

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: A randomized, double-blind, placebo controlled, parallel group, multicentric, phase IIa clinical trial to evaluate the safety, tolerability and therapeutic efficacy of daily oral treatment with NFX88 on neuropathic pain in patients with spinal cord injury.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Safety and tolerability of NFX88 administered by 90 days

Primary: Safety and tolerability of NFX88 administered by 90 days

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A randomized, double-blind, placebo controlled, parallel group, multicentric, phase IIa clinical trial to evaluate the safety, tolerability and therapeutic efficacy of daily oral treatment with NFX88 on neuropathic pain in patients with spinal cord injury.