Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain.

Culver DA, Dahan A, Bajorunas D, Jeziorska M, van Velzen M, Aarts LPHJ, Tavee J, Tannemaat MR, Dunne AN, Kirk RI, Petropoulos IN, Cerami A, Malik RA, Brines M

Investigative ophthalmology & visual science1 May 2017Cited by 79 (Europe PMC)

PMID28475703DOI10.1167/iovs.16-21291PepBankPUB-28475703

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Summary

PurposeSarcoidosis frequently is complicated by small nerve fiber loss (SNFL), which can be quantified using corneal confocal microscopy (CCM). Prior studies suggest that the innate repair receptor agonist cibinetide reverses corneal nerve loss. This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).MethodsCibinetide (1, 4, or 8 mg/day) was compared to placebo. The primary study endpoint was a change in CNFA at 28 days.ResultsThe placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively. Intraepidermal GAP-43+ fibers increased in the 4 mg group (P = 0.035). Further, changes in CNFA correlated with changes in GAP-43+ (ρ = 0.575; P = 0.025) and 6MWT (ρ = 0.645; P = 0.009). Pain improved significantly in all groups, with subjects having moderate-severe pain reporting a clinically meaningful placebo-corrected decrease in pain intensity in the 4 mg group (P = 0.157).ConclusionsCibinetide significantly increased small nerve fiber abundance in the cornea and skin, consistent with a disease modifying effect. The relationships between CNFA and other clinical measures of disease support its use as a surrogate endpoint to assess potential disease modifying therapies for neuropathy.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with sarcoid-associated small nerve fiber loss, cibinetide 1 mg/day did not significantly change corneal nerve fiber area versus placebo at day 28.
In plain wordsIn people with sarcoidosis nerve fiber loss, 1 mg a day of cibinetide did not clearly change corneal nerve fiber area compared with placebo.
Peptide
Cibinetide (ARA-290)
Outcome
No significant changePlacebo-corrected change in corneal nerve fiber area (CNFA) at day 28, 1 mg/day
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
1 mg/day · 28 daysAs given in this study (human).
Measurements
Placebo-corrected CNFA change
109 μm2
1 mg/day
Source sentences
Summary
The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively.
3 context sentences(design, population, supporting numbers)
Summary · context
The primary study endpoint was a change in CNFA at 28 days.
Summary · context
This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).
Summary · context
Cibinetide (1, 4, or 8 mg/day) was compared to placebo.
Show in the study text Report a problemFND-2847570301
02HumanRandomized controlled trialEfficacy outcome
In adults with sarcoid-associated small nerve fiber loss, cibinetide 4 mg/day significantly increased corneal nerve fiber area versus placebo at day 28.
In plain wordsIn people with sarcoidosis nerve fiber loss, 4 mg a day of cibinetide increased corneal nerve fiber area compared with placebo.
Peptide
Cibinetide (ARA-290)
Outcome
IncreasePlacebo-corrected change in corneal nerve fiber area (CNFA) at day 28, 4 mg/day
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
4 mg/day · 28 daysAs given in this study (human).
Measurements
Placebo-corrected CNFA change
697 μm2
4 mg/day
Source sentences
Summary
The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively.
3 context sentences(design, population, supporting numbers)
Summary · context
The primary study endpoint was a change in CNFA at 28 days.
Summary · context
This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).
Summary · context
Cibinetide (1, 4, or 8 mg/day) was compared to placebo.
Show in the study text Report a problemFND-2847570302
03HumanRandomized controlled trialEfficacy outcome
In adults with sarcoid-associated small nerve fiber loss, cibinetide 8 mg/day did not significantly change corneal nerve fiber area versus placebo at day 28.
In plain wordsIn people with sarcoidosis nerve fiber loss, 8 mg a day of cibinetide did not clearly change corneal nerve fiber area compared with placebo.
Peptide
Cibinetide (ARA-290)
Outcome
No significant changePlacebo-corrected change in corneal nerve fiber area (CNFA) at day 28, 8 mg/day
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
8 mg/day · 28 daysAs given in this study (human).
Measurements
Placebo-corrected CNFA change
431 μm2
8 mg/day
Source sentences
Summary
The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively.
3 context sentences(design, population, supporting numbers)
Summary · context
The primary study endpoint was a change in CNFA at 28 days.
Summary · context
This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).
Summary · context
Cibinetide (1, 4, or 8 mg/day) was compared to placebo.
Show in the study text Report a problemFND-2847570303
04HumanRandomized controlled trialEfficacy outcome
In adults with sarcoid-associated small nerve fiber loss and neuropathic pain, pain improved significantly in all groups; the abstract does not say that this differed from placebo.
In plain wordsIn people with sarcoidosis nerve pain, pain improved in all groups; the abstract does not say whether cibinetide did better than placebo.
Peptide
Cibinetide (ARA-290)
Outcome
DecreasePain severity
Study
n = 64
Outcome group
Pain · Nervous system and cognition
Studied dose
1, 4 and 8 mg/day · 28 daysAs given in this study (human).
Source sentences
Summary
Pain improved significantly in all groups
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).
Summary · context
Cibinetide (1, 4, or 8 mg/day) was compared to placebo.
Show in the study text Report a problemFND-2847570307
05HumanRandomized controlled trialEfficacy outcome
In adults with sarcoid-associated small nerve fiber loss, intraepidermal GAP-43+ fibers increased in the cibinetide 4 mg group.
In plain wordsIn people with sarcoidosis nerve fiber loss, regenerating skin nerve fibers increased in the 4 mg cibinetide group.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseIntraepidermal GAP-43+ regenerating fibers
Study
n: not reported in source
Comparator
Placebo
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
4 mg/day · 28 daysAs given in this study (human).
Source sentences
Summary
Intraepidermal GAP-43+ fibers increased in the 4 mg group (P = 0.035).
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).
Summary · context
Cibinetide (1, 4, or 8 mg/day) was compared to placebo.
Show in the study text Report a problemFND-2847570304
06HumanRandomized controlled trialOther
In adults with sarcoid-associated small nerve fiber loss, changes in corneal nerve fiber area correlated with changes in GAP-43+ fibers.
In plain wordsIn people with sarcoidosis nerve fiber loss, changes in corneal nerve fiber area went together with changes in regenerating skin nerve fibers.
Peptide
Cibinetide (ARA-290)
Outcome
Not applicableCorrelation of CNFA change with GAP-43+ change
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
1, 4 and 8 mg/day · 28 daysAs given in this study (human).
Measurements
Correlation coefficient (rho)
0.575 NA
CNFA vs GAP-43+
Source sentences
Summary
Further, changes in CNFA correlated with changes in GAP-43+ (ρ = 0.575; P = 0.025) and 6MWT (ρ = 0.645; P = 0.009).
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).
Summary · context
Cibinetide (1, 4, or 8 mg/day) was compared to placebo.
Show in the study text Report a problemFND-2847570305
07HumanRandomized controlled trialOther
In adults with sarcoid-associated small nerve fiber loss, changes in corneal nerve fiber area correlated with changes in the 6-minute walk test.
In plain wordsIn people with sarcoidosis nerve fiber loss, changes in corneal nerve fiber area went together with changes in walking test results.
Peptide
Cibinetide (ARA-290)
Outcome
Not applicableCorrelation of CNFA change with 6-minute walk test change
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
1, 4 and 8 mg/day · 28 daysAs given in this study (human).
Measurements
Correlation coefficient (rho)
0.645 NA
CNFA vs 6MWT
Source sentences
Summary
Further, changes in CNFA correlated with changes in GAP-43+ (ρ = 0.575; P = 0.025) and 6MWT (ρ = 0.645; P = 0.009).
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).
Summary · context
Cibinetide (1, 4, or 8 mg/day) was compared to placebo.
Show in the study text Report a problemFND-2847570306
08HumanRandomized controlled trialEfficacy outcome
In subjects with moderate-severe pain, the placebo-corrected decrease in pain intensity with cibinetide 4 mg/day was described as clinically meaningful but was not statistically significant (P = 0.157).
In plain wordsIn people with moderate to severe pain, the pain decrease with 4 mg of cibinetide versus placebo was not statistically significant (P = 0.157).
Peptide
Cibinetide (ARA-290)
Outcome
No significant changePlacebo-corrected pain intensity in moderate-severe pain
Study
n: not reported in source
Comparator
Placebo
Outcome group
Pain · Nervous system and cognition
Studied dose
4 mg/day · 28 daysAs given in this study (human).
Source sentences
Summary
with subjects having moderate-severe pain reporting a clinically meaningful placebo-corrected decrease in pain intensity in the 4 mg group (P = 0.157).
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).
Summary · context
Cibinetide (1, 4, or 8 mg/day) was compared to placebo.
Show in the study text Report a problemFND-2847570308

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

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