PF-07275315 + PF-07264660 for Eczema
Recruiting in Palo Alto (17 mi)
+70 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Pfizer
Must not be taking: Systemic immunosuppressants, Antimicrobials
Disqualifiers: SLE, Type 1 diabetes, IBD, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is testing two new medicines, PF-07275315 and PF-07264660, given as shots to adults with moderate to severe atopic dermatitis that hasn't improved with other treatments. The goal is to see if these medicines are safe and effective in reducing the symptoms of this itchy red rash.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, it mentions that you cannot use certain prohibited medications during the study. It's best to discuss your current medications with the study team to see if any changes are needed.
What data supports the effectiveness of the drug PF-07275315 + PF-07264660 for eczema?
What makes the drug PF-07275315 + PF-07264660 unique for treating eczema?
The drug PF-07275315 + PF-07264660 is unique because it targets specific immune pathways by blocking the action of certain cytokines (proteins important in cell signaling) like IL-4, IL-13, and TSLP, which are involved in the inflammatory process of eczema. This approach is different from traditional treatments like tacrolimus, which primarily suppresses immune cell activity more broadly.678910
Eligibility Criteria
Adults over 18 with moderate to severe atopic dermatitis (AD), diagnosed at least 6 months ago, who haven't responded well to topical treatments or for whom these are not suitable. Participants must have a BMI of 17.5-40 and weigh over 45 kg. Exclusions include significant allergies or autoimmune diseases, recent serious infections, other skin conditions that could affect AD assessment, psychiatric risks, prohibited medication use, recent phototherapy or investigational drug use.Inclusion Criteria
My BMI is between 17.5 and 40, and I weigh more than 100 lbs.
I have had chronic atopic dermatitis for over 6 months, with treatments not working well.
Exclusion Criteria
Significant allergic or autoimmune diseases, other than AD and well controlled mild to moderate including but not limited to: SLE or other complement disorders; Type 1 diabetes; Irritable bowel syndrome; Multiple Sclerosis
History of significant allergic reactions, including anaphylaxis and reactions to protein therapeutics, except to single, identified, avoidable allergens (eg, peanut allergy)
Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive PF-07275315, PF-07264660, or placebo as multiple injections over 12 weeks
12 weeks
Stage 1: 8 visits, Stage 2: 4 visits
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 weeks
Treatment Details
Interventions
- PF-07264660 (Monoclonal Antibodies)
- PF-07275315 (Monoclonal Antibodies)
- Placebo (Other)
Trial OverviewThe trial is testing two potential medications for AD: PF-07275315 and PF-07264660 against a placebo. These are administered as injections in the clinic across different schedules in Stage 1 and Stage 2 of the study. The trial aims to determine their safety and effectiveness by comparing outcomes between those receiving the drugs and those on placebo over up to an approximately 20-month period.
Participant Groups
8Treatment groups
Experimental Treatment
Group I: Stage 2_PlaceboExperimental Treatment1 Intervention
Stage 2 Placebo Injections on Day 1, Week 4, Week 8 and Week 12.
Group II: Stage 2_PF-07275315 or PF-07264660_Dose DExperimental Treatment2 Interventions
Stage 2 PF-07275315 or PF-07264660 Injections on Day 1, Week 4, Week 8 and Week 12.
Group III: Stage 2_PF-07275315 or PF-07264660_Dose CExperimental Treatment2 Interventions
Stage 2 PF-07275315 or PF-07264660 Injections on Day 1, Week 4, Week 8 and Week 12.
Group IV: Stage 2_PF-07275315 or PF-07264660_Dose BExperimental Treatment2 Interventions
Stage 2 PF-07275315 or PF-07264660 Injections on Day 1, Week 4, Week 8 and Week 12.
Group V: Stage 2_PF-07275315 or PF-07264660_Dose AExperimental Treatment2 Interventions
Stage 2 PF-07275315 or PF-07264660 Injections on Day 1, Week 4, Week 8 and Week 12.
Group VI: Stage 1_PlaceboExperimental Treatment1 Intervention
Stage 1 Placebo Injections on Day 1, Week 1, Week 2, Week 4, Week 6, Week 8, Week 10 and Week 12.
Group VII: Stage 1_PF-07275315Experimental Treatment1 Intervention
Stage 1 PF-07275315 Injections on Day 1, Week 1, Week 2, Week 4, Week 6, Week 8, Week 10 and Week 12.
Group VIII: Stage 1_PF-07264660Experimental Treatment1 Intervention
Stage 1 PF-07264660 Injections on Day 1, Week 1, Week 2, Week 4, Week 6, Week 8, Week 10 and Week 12.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
DermEdge ResearchMississauga, Canada
DCT-Stone Oak, LLC dba Discovery Clinical TrialsSan Antonio, TX
Spartanburg Medical ResearchSpartanburg, SC
Wiseman Dermatology Research Inc.Winnipeg, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
PfizerLead Sponsor
References
Dupilumab treatment improves quality of life in adult patients with moderate-to-severe atopic dermatitis: results from a randomized, placebo-controlled clinical trial. [2019]Dupilumab, a human anti-interleukin-4 receptor alpha monoclonal antibody, significantly improved clinical signs and symptoms in adults with moderate-to-severe atopic dermatitis in a randomized, double-blind, placebo-controlled, phase IIa trial.
Placebo response in phase 2 and 3 trials of systemic and biological therapies for atopic dermatitis-a systematic review and meta-analysis. [2021]A growing number of clinical trials of biological and systemic therapies have been conducted within adult atopic dermatitis (AD). No study has yet examined and meta-analysed the pooled placebo response in AD. We performed a systematic review and meta-analysis to examine the placebo response in clinical trials evaluating the effect of systemic and biological therapies in adult AD and compared it to results from clinical trials in psoriasis. Two screeners independently searched the databases ClinicalTrials.gov, Embase, Pubmed and Web of Science. A total of 2058 articles were identified, of which 78 were full-text reviewed. Overall, 25 trials were included in the qualitative analysis, of which 24 were further included in the quantitative analysis. At 12-week follow-up, EASI50, EASI75 and EASI90 placebo responses were 39.9% [95% confidence interval (CI), 36.7-43.2], 20.9% (95% CI, 18.2-23.8) and 9.0% (95% CI, 6.7-11.6), respectively. At week 12, the pooled proportion of placebo-treated AD patients that obtained EASI50, EASI75 and EASI90 was significantly higher than the pooled proportion of placebo-treated psoriasis patients obtaining PASI50, PASI75 and PASI90 (P
Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). [2022]Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis (AD).
Association of polymorphisms in genes encoding IL-4, IL-13 and their receptors with atopic dermatitis in a Korean population. [2022]Th2-dominated immune responses are believed to contribute to the pathogenesis of atopic dermatitis (AD). IL-4 and IL-13 are typical pleiotropic Th2 cytokines that play a central role in IgE-dependent inflammatory reactions. Single-nucleotide polymorphisms (SNPs) in IL-4 and IL-13 have been reported in patients with allergic disease from numerous countries. Gene-gene interactions among genes have been identified in patients with asthma, although negative results have been reported. To investigate the associations of SNPs in these genes and the interactions between these genes in AD, we genotyped 23 SNPs of the IL-4, IL-13, IL-4R, IL-13Rα1 and IL-13Rα2 genes for 1089 case-control samples (631 AD patients and 458 controls) and analysed the SNPs and haplotypes in these genes. We also searched for gene-gene interactions among these five genes. Our data identified an association between rs3091307 and rs20541 in the IL-13 gene and between rs2265753 and rs2254672 in the IL-13Rα1 gene and the AD phenotype. In particular, three of the four SNPs were especially predictive of the allergic type of AD (ADe), and the haplotype TCGG in the IL-13Rα1 gene showed significant association with AD, especially ADe. Furthermore, the combination of rs3091307 GG/ rs2265753 GG (IL-13/IL-13Rα1) conveyed a significantly higher risk for developing ADe. However, we did not identify any SNPs in the IL-4, IL-4R and IL-13Rα2 genes that were associated with AD. As IL-13Rα1 is most likely expressed in Th17 cells rather than in Th2 cells, these data suggest diversity in the classification of Th cells that needs to be verified in future studies.
TNF-like weak inducer of apoptosis inhibition is comparable to IL-13 blockade in ameliorating atopic dermatitis inflammation. [2023]Targeting IL-13 is highly efficacious in patients with Th2-biased atopic dermatitis (AD), but inhibition of other inflammatory molecules might also limit disease. We investigated the importance of the TNF family cytokine TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) to keratinocyte dysregulation and the pathogenesis of AD in mice and also tested if blocking TWEAK has a similar therapeutic effect as targeting IL-13.
Topical application of FK506 (tacrolimus) ointment inhibits mite antigen-induced dermatitis by local action in NC/Nga mice. [2017]FK506 ointment (tacrolimus ointment, protopic) is a new drug therapeutically effective for patients with atopic dermatitis (AD). However, the mechanism of action of FK506 ointment on AD is not fully understood.
Regulation of entheseal IL-23 expression by IL-4 and IL-13 as an explanation for arthropathy development under dupilumab therapy. [2021]Dupilumab blocks the IL-4 receptor (IL-4R) and thus signalling of the 'Th2' cytokines IL-4 and IL-13. It has a license to treat atopic eczema and was recently linked to emergent enthesitis and psoriasis. We investigated the cellular and functional basis for how IL-4/IL-13 regulates the IL-23-IL-17 axis in entheseal stromal, myeloid and lymphocyte cells.
Tacrolimus pharmacology and nonclinical studies: from FK506 to protopic. [2021]Tacrolimus (FK506) is a calcineurin inhibitor with potent immunomodulating properties. It has been marketed worldwide since 1993-1994 for the rejection of liver and kidney transplants (Prograf). The pharmacologic properties of tacrolimus resulted in its development as an ointment for the treatment of atopic dermatitis. An outline of nonclinical pharmacology studies that provided a rationale for this development is presented. The key nonclinical toxicology-safety studies that supported clinical efficacy/safety trials are also discussed. Taken collectively, these studies contributed to the marketing approval of 0.03% and 0.1% tacrolimus ointment (Protopic) as a first in class treatment for atopic dermatitis.
Effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga mice. [2019]The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga (NC) mice was examined. FK506 ointment (0.1-1%) suppressed the development of dermatitis and was also therapeutically effective against established dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells, eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed in the skin of the NC mice, and FK506 ointment suppressed all of these changes. Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506 ointment reduced the plasma IgE level. These results suggested that FK506 suppressed the dermatitis by inhibiting the activation of inflammatory cells and by blocking the cytokine network in the skin of the NC mice. The commercially available steroid ointments showed only marginal effect on the development of dermatitis and showed some signs of side effects such as alopecia or atrophy of the skin. The effect of the steroids might have been masked by these side effects because the steroids showed similar inhibitory effects on the skin histopathological changes and the increase of plasma IgE. From these results, FK506 ointment can be expected to be a useful drug for atopic dermatitis.
Tacrolimus: a review of its use for the management of dermatoses. [2022]The newly developed immunomodulator tacrolimus (FK506) is the first of a new class of agents that have enormous potential to change the way that dermatoses are treated and managed. Tacrolimus has been found to be active in a topical formulation with the latter exerting its effects by acting on the signal transduction pathways inside T cells and inhibiting gene transcription. The result is decreased responsiveness of T cells to antigens. Percutaneous absorption of tacrolimus is higher in diseased skin as opposed to healthy skin and, therefore, the drug will be taken in at progressively lower quantities as lesions heal. There is limited systemic absorption of tacrolimus over the course of therapy. The most extensive experience with tacrolimus has been in treating atopic dermatitis. In numerous trials, tacrolimus ointment 0.03-0.3% has shown to be effective in reducing the symptoms and severity of atopic dermatitis in adults and the paediatric population. Furthermore, there have been no significant toxic effects associated with topical therapy with tacrolimus. The most common complaint is that of local irritation after applying the ointment. This is generally transient and the patient is able to continue with therapy. The other dermatoses where tacrolimus has been used include contact dermatitis, psoriasis and pyoderma gangrenosum.