A Phase 2 Multicenter Study to Evaluate PF-06823859 in Adult Participants With Active CLE or SLE With Cutaneous Manifestations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

21 Dec 2023 → 18 Nov 2025

Decision date (initial)

2023-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-503343-33-00

ClinicalTrials.gov

NCT05879718

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Pharmacokinetic

To evaluate the effect of PF 06823859 on the type 1IFN GS score at Week 12 in participants with CLE or SLE with cutaneous manifestations

Secondary objectives 4

1. To evaluate the effect of PF 06823859 on the CLASI A score at Week 12 in participants with CLE or SLE with cutaneous manifestations
2. To evaluate the effect of PF-06823859 on the additional measures of CLASI-A score at Week 12 and over time in participants with CLE or SLE with cutaneous manifestations
3. To evaluate the effect of PF-06823859 on the PhGA in participants with CLE or SLE with cutaneous manifestations
4. To evaluate the safety and tolerability of PF-06823859 in participants with CLE or SLE with cutaneous manifestations

Conditions and MedDRA coding

Active Cutaneous Lupus Erythematosus (CLE) or Systemic Lupus Erythematosus (SLE) With Cutaneous Manifestations

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female participants between the ages of 18 (or the minimum country specific age of consent if >18) and 75 years, inclusive, at the time of signing the ICD.
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Participants must be willing to avoid application of topical medications to the index lesions (4 index lesions should be identified at screening and baseline) that are identified for potential biopsies in the study until after Week 32.
4. Participants must have adequate IV access for administration of study intervention and on-study blood sampling.
5. Have a diagnosis of histologically confirmed active CLE or SLE with cutaneous manifestations despite treatment with standard of care medications for at least 12 weeks defined as a score of ≥8 on the CLASI-A, an erythema score of ≥2 in the CLASI and historical biopsy (report to be available to disease activity adjudicators) within the past 10 years with either: a. Subacute cutaneous lupus erythematosus, or b. Discoid lupus erythematosus with at least one active discoid lesion (panniculitis, tumidus and chilblain lesions are excluded for the purposes of disease activity qualifying for eligibility and biopsy but are not exclusionary), or c. Both subacute and chronic cutaneous lupus erythematosus
6. All participants may be currently receiving EITHER a stable dose of an immunosuppressant (MTX, AZA, 6-MP, leflunomide, mizoribine, MMF), or dapsone or colchicine with or without antimalarials and/or corticosteroids, OR anti-malarials (hydroxychloroquine, chloroquine or quinacrine) in combination with corticosteroids (dose of oral corticosteroids must be between 5 and 10 mg/day prednisone equivalent) or permitted topical agents.
7. Participants weighing greater than 40 kg and less than 130 kg and with a BMI of <40 kg/m2.

Exclusion criteria 29

1. Have another skin disorder that would confound the results of the skin biopsy or clinical assessments in the study.
2. Screening chest X-ray with changes suggestive of active infection, prior untreated TB, heart failure, suspected malignancy, or any other clinically significant disease in the chest.
3. Active, severe lupus nephritis that requires or may require treatment with cytotoxic agents or high-dose CS.
4. Infected with Mycobacterium TB: active TB or latent TB.
5. Known history of HIV based on documented history with positive test, or positive HIV test at screening.
6. Have evidence of active or latent infection of hepatitis B or hepatitis C based on screening tests.
7. Screening 12-lead ECG that demonstrates clinically significant abnormalities requiring treatment or that are indicative of serious underlying heart disease and other clinically relevant abnormalities which may affect participant safety or interpretation of study results.
8. Clinically significant lab abnormalities.
9. Investigator or site staff directly involved in the conduct of the study and their family members.
10. Significant trauma or major surgery or blood transfusion within 5 weeks of screening, or scheduled to occur during the study, excluding diagnostic surgery.
11. History of alcohol or drug abuse in investigator’s opinion unless in full remission for greater than 12 months prior to first dose of study intervention.
12. History (single episode) of disseminated herpes zoster or disseminated herpes simplex, or recurrent (more than 1 episode within last 5 years) localized, dermatomal herpes zoster.
13. Participants who are currently vaping or using e-cigarettes.
14. Severe active CNS lupus requiring therapeutic intervention within 60 days of Day 1.
15. Cancer or any history of cancer within 5 years of screening (except adequately resected skin basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix without recurrence within the previous 5 years).
16. History of a major organ transplant or hematopoietic stem cell/marrow transplant or total lymphoid irradiation.
17. Have a history of: • A history of major cardiovascular or cerebrovascular event (stroke) or acute cardiac syndrome (MI, unstable angina pectoris, coronary stenting) within 24 months of screening. • known pulmonary arterial hypertension, • history of pulmonary embolism within 6 months of screening.
18. Preexisting demyelinating disorder such as multiple sclerosis, or other severe neurological deficits.
19. Have any autoimmune or inflammatory disease that would interfere with interpretation of test results or clinical assessments.
20. History of any lymphoproliferative disorder such as EBV related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of lymphoproliferative disease, including lymphadenopathy or splenomegaly.
21. Other 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.
22. Have required management of acute or chronic infections.
23. Additional immunomodulatory drug exclusions.
24. Have received plasmapheresis within 12 weeks of screening or IVIg within 24 weeks of screening.
25. Treatment with any investigational drug(s) within 12 weeks of Day 1 for investigational biologics or within one month or 5 half-lives for investigational small molecules whichever is longer, and/or during study participation.
26. Has been exposed to a live vaccine within 8 weeks of Day 1 or are expected to need/receive a live vaccine during the course of the study. Participants should not have received a BCG vaccination within 52 weeks of randomization.
27. Use of filgrastim, pegfilgrastim, erythropoietin or other bone marrow stimulants to improve cell counts within 12-week of screening.
28. Participation in other interventional studies within 12 weeks or 5 half-lives, if known, whichever is longer, prior to study entry and/or during study participation.
29. Participants with a history of hypersensitivity reactions to active drug or any of the excipients in the rug product or placebo.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in type 1 IFN GS score in lesional skin at Week 12

Secondary endpoints 4

1. Change from baseline (%) in CLASI A score at Week 12
2. Percent change from baseline in CLASI-A (over time in addition to Week 12). Change from baseline in CLASI-A (over time). Achieving ≥50%, 4 or 7 points reduction in CLASI-A (over time)
3. Change from baseline in PhGA (over time)
4. Incidence and severity of laboratory, vital signs, 12-lead ECG abnormalities, AEs, SAEs and withdrawals due to AEs over time

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 3

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications