Evidence map›Paper›PMID 32767679›Full record

Trial reportClinical and experimental dermatology2021

A phase I, randomized, double-blind study to assess the safety, tolerability and efficacy of the topical RORC2 inverse agonist PF-06763809 in participants with mild-to-moderate plaque psoriasis.

G Berstein, Y Zhang, Z Berger, E Kieras, G Li, A Samuel, T Yeoh, H Dowty, K Beaumont, W Wigger-Alberti and 7 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical and experimental dermatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03469336 (A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE AND ACTIVE COMPARATOR-CONTROLLED, PSORIASIS PLAQUE TEST STUDY TO ASSESS SAFETY, TOLERABILITY, AND PSORIATIC SKIN INFILTRATE THICKNESS FOLLOWING REPEATED, TOPICAL DOSES OF PF-06763809 SOLUTION IN SUBJECTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03469336 phase1completednot on this map

A phase 1, randomized, double-blind, vehicle and active comparator-controlled, psoriasis plaque test study to assess safety, tolerability, and psoriatic skin infiltrate thickness following repeated, topical doses of pf-06763809 solution in subjects with mild to moderate chronic plaque psoriasis

TypeinterventionalSponsorPfizerRan2018 to 2019Enrolled18ConditionsPsoriasisArmsPF-06763809, Vehicle, Calcipotriene/calcipotriol, Betamethasone
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

G BersteinInflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, USA.
Y ZhangInflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, USA.
Z BergerInflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, USA.
E KierasInflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, USA.
G LiEarly Clinical Development, Pfizer Inc., Collegeville, PA, USA.
A SamuelFormulation and Process Design, Pfizer Inc., Groton, CT, USA.
T YeohFormulation and Process Design, Pfizer Inc., Groton, CT, USA.
H DowtyInflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, USA.
K BeaumontInflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, USA.
W Wigger-AlbertiBioskin GmbH, Hamburg, Germany.
Y von MackensenBioskin GmbH, Hamburg, Germany.
U KroenckeBioskin GmbH, Hamburg, Germany.
R HamschoRothhaar Studien GmbH, Berlin, Germany.
S GarcetRockefeller University, New York, NY, USA.
J G KruegerRockefeller University, New York, NY, USA.
C BanfieldInflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, USA.
B OemarInflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, USA.
Pfizer (United States) · USBioglobe (Germany) · DERockefeller University · USRoth and Rau (Germany) · DE

Funding

Pfizer Inc.
6 · The paper itself

Abstract

backgroundTranscription factor retinoic acid-related orphan receptor 2 (RORC2/RORγT) mediates interleukin (IL)-17A and IL-17F expression. IL-17A plays a central role in the pathogenesis of several inflammatory disorders, including psoriasis. The RORC2 inhibitor PF-06763809 has been hypothesized to inhibit IL-17A production in T-helper 17 (Th17) cells, thereby reducing psoriasis symptoms.

aimTo assess the safety, tolerability and effect on skin infiltrate thickness of PF-06763809 in participants with mild/moderate chronic plaque psoriasis.

methodsThis was a randomized, double-blind, first-in-human study (trial registration: ClinicalTrials.gov NCT03469336). Participants received each of the following six treatments once daily for 18 days: three topical doses (2.3%, 0.8%, 0.23%) of PF-06763809, a vehicle and two active comparators (betamethasone and calcipotriol). Primary endpoints included change from baseline in psoriatic skin infiltrate thickness [echo-poor band (EPB) on ultrasonography] at Day 19, and safety. Change in psoriasis-associated gene expression (Day 19), evaluated by real-time reverse transcription PCR of skin biopsies, was an exploratory endpoint.

resultsIn total, 17 participants completed the study. Change from baseline in the EPB on Day 19 for all three doses of PF-06763809 was not significantly different from that of vehicle (P > 0.05). A significant reduction in EPB from baseline was observed with betamethasone on Day 19 relative to all other treatments (P < 0.0001). Treatment-related adverse events were mild/moderate. There were no significant differences in gene expression on Day 19 between vehicle and PF-06763809-treated skin lesions.

conclusionUsing a psoriasis plaque test design, PF-06763809 was found to be well tolerated with an acceptable safety profile in participants with psoriasis, but without reduction in skin infiltrate thickness or disease biomarkers.

Indexed as

Administration, TopicalBoron CompoundsBridged Bicyclo Compounds, HeterocyclicDouble-Blind MethodGene ExpressionHumansInterleukin-17MaleMiddle AgedNuclear Receptor Subfamily 1, Group F, Member 3Organic ChemicalsPsoriasisReal-Time Polymerase Chain ReactionSkinTreatment FailureBoron CompoundsBridged Bicyclo Compounds, HeterocycliccrisaboroleIL17A protein, humanInterleukin-17Nuclear Receptor Subfamily 1, Group F, Member 3Organic Chemicalspf-06763809RORC protein, human

Identifiers

PMID32767679
PMCPMC7756278
OpenAlexW3048160446

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.