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?

Research shows that targeting IL-13, a key player in inflammation, is effective in treating atopic dermatitis (a type of eczema). Since PF-07275315 + PF-07264660 involves anti-IL4/13/TSLP, which likely targets similar pathways, it may also help reduce eczema symptoms. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

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

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 Overview The 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

Group I: Stage 2_Placebo Experimental Treatment 1 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 D Experimental Treatment 2 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 C Experimental Treatment 2 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 B Experimental Treatment 2 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 A Experimental Treatment 2 Interventions

Stage 2 PF-07275315 or PF-07264660 Injections on Day 1, Week 4, Week 8 and Week 12.

Group VI: Stage 1_Placebo Experimental Treatment 1 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-07275315 Experimental Treatment 1 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-07264660 Experimental Treatment 1 Intervention

Stage 1 PF-07264660 Injections on Day 1, Week 1, Week 2, Week 4, Week 6, Week 8, Week 10 and Week 12.

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

In a phase IIa trial involving 64 adults with moderate-to-severe atopic dermatitis, dupilumab significantly improved health-related quality of life (HRQoL) as measured by the Quality of Life Index of Atopic Dermatitis (QoLIAD) after 12 weeks compared to placebo, with a mean percentage change of -64.0% versus -11.1%.

Improvements in QoLIAD scores were strongly correlated with clinical efficacy outcomes, such as the Eczema Area and Severity Index (EASI) and various pruritus scales, indicating that dupilumab not only enhances quality of life but also effectively reduces the severity of atopic dermatitis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab treatment improves quality of life in adult patients with moderate-to-severe atopic dermatitis: results from a randomized, placebo-controlled clinical trial. Tsianakas, A., Luger, TA., Radin, A.[2019]

In a systematic review and meta-analysis of 25 clinical trials involving adult atopic dermatitis (AD), the placebo response rates at 12 weeks were found to be 39.9% for EASI50, 20.9% for EASI75, and 9.0% for EASI90, indicating a notable response even without active treatment.

The study revealed that the placebo response in AD patients was significantly higher than that observed in psoriasis patients, highlighting the unique and fluctuating nature of AD and the importance of consistent topical treatment to manage disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo response in phase 2 and 3 trials of systemic and biological therapies for atopic dermatitis-a systematic review and meta-analysis. Andreasen, TH., Christensen, MO., Halling, AS., et al.[2021]

In a phase 2 study involving 209 adults with moderate-to-severe atopic dermatitis, lebrikizumab 125 mg administered every 4 weeks significantly improved skin condition, with 82.4% of patients achieving at least a 50% reduction in eczema severity compared to 62.3% in the placebo group.

The safety profile of lebrikizumab was comparable to placebo, with most adverse events being mild or moderate, indicating that it can be safely used as an add-on therapy to topical corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Simpson, EL., Flohr, C., Eichenfield, LF., et al.[2022]

A study involving 1089 participants (631 with atopic dermatitis and 458 controls) identified specific single-nucleotide polymorphisms (SNPs) in the IL-13 and IL-13Rα1 genes that are associated with an increased risk of developing atopic dermatitis, particularly the allergic type (ADe).

The haplotype TCGG in the IL-13Rα1 gene was significantly linked to ADe, suggesting that gene interactions, particularly between IL-13 and IL-13Rα1, play a crucial role in the pathogenesis of atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of polymorphisms in genes encoding IL-4, IL-13 and their receptors with atopic dermatitis in a Korean population. Namkung, JH., Lee, JE., Kim, E., et al.[2022]

Mice lacking the TWEAK receptor (Fn14) in keratinocytes showed resistance to severe atopic dermatitis (AD) symptoms, indicating that TWEAK plays a significant role in the disease's development.

Blocking TWEAK in wild-type mice with AD resulted in a reduction of skin inflammation and other pathological features, demonstrating that targeting TWEAK could be as effective as targeting IL-13 for treating AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TNF-like weak inducer of apoptosis inhibition is comparable to IL-13 blockade in ameliorating atopic dermatitis inflammation. Gupta, RK., Miller, J., Croft, M.[2023]

Tacrolimus hydrate (FK506) ointment effectively suppressed both the development and severity of spontaneous dermatitis in NC/Nga mice, demonstrating its therapeutic potential against established dermatitis.

FK506 ointment reduced inflammatory markers such as CD4-positive T cells, mast cells, eosinophils, and plasma IgE levels, suggesting it works by inhibiting inflammatory cell activation and blocking cytokine activity, making it a promising alternative to traditional steroid treatments that may have side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga mice. Hiroi, J., Sengoku, T., Morita, K., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Dupilumab treatment improves quality of life in adult patients with moderate-to-severe atopic dermatitis: results from a randomized, placebo-controlled clinical trial. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Placebo response in phase 2 and 3 trials of systemic and biological therapies for atopic dermatitis-a systematic review and meta-analysis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

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]

4. Denmark pubmed.ncbi.nlm.nih.gov

Association of polymorphisms in genes encoding IL-4, IL-13 and their receptors with atopic dermatitis in a Korean population. [2022]

5. Denmark pubmed.ncbi.nlm.nih.gov

TNF-like weak inducer of apoptosis inhibition is comparable to IL-13 blockade in ameliorating atopic dermatitis inflammation. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Topical application of FK506 (tacrolimus) ointment inhibits mite antigen-induced dermatitis by local action in NC/Nga mice. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Regulation of entheseal IL-23 expression by IL-4 and IL-13 as an explanation for arthropathy development under dupilumab therapy. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Tacrolimus pharmacology and nonclinical studies: from FK506 to protopic. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

Effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga mice. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Tacrolimus: a review of its use for the management of dermatoses. [2022]