Clinical trial NCT04999839: Study of NDI-034858 in Participants With Moderate to Severe Plaque Psoriasis
Official title: A Phase 2b, Randomized, Multicenter, Double-blind, Placebo-controlled, Multiple-dose Study to Evaluate the Efficacy, Safety, and Tolerability of NDI-034858 in Subjects With Moderate to Severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Moderate to Severe Plaque Psoriasis
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Innovaderm Research Inc.
name: Nimbus Lakshmi, Inc.
First posted: 2021-08-11
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2b, randomized, multicenter, double-blind, placebo-controlled, multiple-dose study designed to evaluate the efficacy, safety, and tolerability of NDI-034858 in participants with moderate to severe plaque psoriasis. This study will also evaluate the plasma concentrations of NDI-034858 and explore the immune response to NDI-034858 in participants with moderate to severe plaque psoriasis.

Detailed description: Approximately 259 male and female participants, aged 18 to 70 years (inclusive) were enrolled in this study. Participants were randomized to receive either one of the four doses of NDI-034858, or placebo on Day 1. The goal was to have approximately 50 participants randomized per treatment group (1:1:1:1:1 ratio) on Day 1. During the treatment period, NDI-034858 or placebo was orally administered QD for 12 weeks. The 12 week treatment period was followed by a 4-week safety follow-up period.

Eligibility criteria: Inclusion Criteria:

In order to be eligible to participate in this study, a participant must meet all of the following criteria, either at the screening and Day 1 visits or only at one of the specified visits (screening or Day 1) as noted in the criterion:

1. Male or female participant aged 18 to 70 years, inclusive, at the time of consent.
2. Participant has a history of plaque psoriasis for at least 6 months prior to the screening visit.
3. Participant had no significant flare in psoriasis for at least 3 months before screening (information obtained from medical chart or participant's physician, or directly from the participant).
4. Participant has moderate to severe plaque psoriasis as defined by a PASI score ≥ 12 and a PGA score ≥ 3 at screening and Day 1.
5. Participant has plaque psoriasis covering ≥ 10% of his or her total BSA at screening and Day 1.
6. Participant must be a candidate for phototherapy or systemic therapy.
7. For female participants of childbearing potential involved in any sexual intercourse that could lead to pregnancy: the participant must agree to use a highly effective contraceptive method from at least 4 weeks prior to Day 1 until at least 4 weeks after the last study product administration. Highly effective contraceptive methods include hormonal contraceptives (eg, combined oral contraceptive, patch, vaginal ring, injectable, or implant), intrauterine devices or intrauterine systems, vasectomized partner(s) (provided vasectomy was performed ≥ 4 months prior to screening), bilateral tubal ligation or occlusion, or double barrier methods of contraception (eg, male condom with cervical cap, male condom with diaphragm, and male condom with contraceptive sponge) in conjunction with spermicide.
8. Female participants of childbearing potential have had a negative serum pregnancy test at screening and negative urine pregnancy test at Day 1.
9. For male participants involved in any sexual intercourse that could lead to pregnancy, participant must agree to use one of the highly effective contraceptive methods listed in Inclusion Criterion 6, from Day 1 until at least 12 weeks after the last study product administration. If the female partner of a male participant uses any of the hormonal contraceptive methods listed above, this contraceptive method should be used by the female partner from at least 4 weeks before Day 1 until at least 12 weeks after the last study product administration.
10. Participant has a BMI within the range of 18 to 42 kg/m2, inclusive (BMI = weight \[kg\]/\[height (m)\]2), and total body weight \>50 kg (110 lb).
11. Participant is willing to participate and is capable of giving informed consent. Note: Consent must be obtained prior to any study-related procedures.
12. Participant must be willing to comply with all study procedures and must be available for the duration of the study.

Exclusion Criteria:

A participant who meets any of the following criteria at the screening and/or Day 1 visits, as applicable, will be excluded from participation in this study:

1. Participant is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.
2. Participant has evidence of erythrodermic, pustular, predominantly guttate psoriasis, or drug induced psoriasis.
3. Participant has a history of skin disease or presence of skin condition that, in the opinion of the investigator, would interfere with the study assessments.
4. Participant has immune-mediated conditions commonly associated with psoriasis, such as psoriatic arthritis, uveitis, inflammatory bowel disease, that require systemic treatment (including corticosteroids, immunosuppressants, or biologics). Note: Participants with immune-mediated conditions that do not require systemic treatment may be included in the study. Certain therapies such as NSAIDs may be permitted, but should be discussed with the Medical Monitor prior to determination of participant eligibility.
5. Participant has any clinically significant medical condition, evidence of an unstable clinical condition (eg, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic, or local active infection/infectious illness), psychiatric condition, or vital signs/physical/laboratory/ECG abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of study results.
6. Participant had a major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study.
7. Participant has a history of Class III or IV congestive heart failure as defined by New York Heart Association Criteria.
8. Participant has been hospitalized in the past 3 months for asthma, has ever required intubation for treatment of asthma, currently require oral corticosteroids for the treatment of asthma, or has required more than one short-term (≤ 2 weeks) course of oral corticosteroids for asthma within 6 months prior to Day 1.
9. Participant has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. Participant with successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded.
10. Participant has a history of fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection within 4 weeks prior to Day 1.
11. Participant has an active bacterial, viral, fungal, mycobacterial infection, or other infection (including TB or atypical mycobacterial disease), or any major episode of infection that required hospitalization or treatment with intravenous antibiotics within 12 weeks prior to Day 1, or oral antibiotics within 4 weeks prior to Day 1.
12. Participant has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection, recurrent urinary tract infection, fungal infection (with the exception of superficial fungal infection of the nailbed), or infected skin wounds or ulcers.
13. Participant has a history of an infected joint prosthesis or has received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
14. Participant has active herpes infection, including herpes simplex 1 and 2 and herpes zoster (demonstrated on physical examination and/or medical history) within 8 weeks prior to Day 1.
15. Participant has a history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the participant's immune status in the opinion of the investigator (eg, history of splenectomy, primary immunodeficiency).
16. Participant has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core antigens (anti-HBc), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
17. Participant has clinical or laboratory evidence of active or latent TB infection at screening.
18. Participant with any of the following laboratory values at the screening visit:

    1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values ≥ 3 times the upper limit of normal (ULN);
    2. Hemoglobin \< 11.0 g/dL (\< 110.0 g/L);
    3. White blood cell count \< 3.5 x 109/L (\< 3500/mm3);
    4. Absolute neutrophil count of \< 1.8 x 109/L (\< 1800/mm3);
    5. Absolute lymphocyte count of \< 1.0 x 109/L (\< 1000/mm3);
    6. Platelet count \< 100 x 109/L (\< 100,000/mm3);
    7. Total bilirubin ˃ 2 times the ULN.
19. Participant who have given \> 50 ml of blood or plasma within 30 days of screening or \> 500 mL of blood or plasma within 56 days of screening (during a clinical study or at a blood bank donation).
20. Participant has used any topical medication that could affect psoriasis (including corticosteroids, retinoids, vitamin D analogues \[such as calcipotriol\], JAK inhibitors, or tar) within 2 weeks prior to Day 1.
21. Participant has used any systemic treatment that could affect psoriasis (including oral, intravenous, intraarticular, intrathecal, intramuscular, or intralesional corticosteroids, oral retinoids, immunosuppressive/immunomodulating medication, methotrexate, cyclosporine, oral JAK inhibitors, or apremilast) within 4 weeks prior to Day 1.
22. Participant has received any UV-B phototherapy (including tanning beds) or excimer laser within 4 weeks prior to Day 1.
23. Participant has had PUVA treatment within 4 weeks prior to Day 1.
24. Participant has received any live-attenuated vaccine within 4 weeks prior to Day 1 or plans to receive a live-attenuated vaccine during the study and up to 4 weeks or 5 half lives of the study product, whichever is longer, after the last study product administration. Note: Nonlive-attenuated vaccines or boosters for Coronavirus Disease 2019 (COVID-19) (eg, RNA-based vaccines, inactivated adenovirus-based vaccines, protein-based vaccines) are allowed during the study. The study site should follow local guidelines related to COVID-19.
25. Participant is currently receiving a nonbiological investigational product or device or has received one within 4 weeks prior to Day 1.
26. Participant has received any marketed or investigational biological agent within 12 weeks or 5 half-lives (whichever is longer) prior to Day 1 (except those listed in Exclusion Criterion 27 and 28 that are to be excluded for 6 months).
27. Participant was previously enrolled in any study with NDI-034858.
28. Participant has a history of lack of response to any therapeutic agent targeting IL-12, IL-17, and/or IL 23 (eg, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, risankizumab) at approved doses after at least 12 weeks of therapy, and/or received one of these therapies within 6 months prior to Day 1.
29. Participant has received rituximab or other immune-cell depleting therapy within 6 months.
30. Participant is currently being treated with strong or moderate cytochrome P450 3A (CYP3A4) inhibitors (such as itraconazole), or has received moderate or strong CYP3A4 inhibitors within 4 weeks prior to Day 1.
31. Participant is currently being treated with terbinafine, or has received terbinafine within 4 weeks prior to Day 1.
32. Participant has consumed grapefruit within 1 week prior to Day 1.
33. Participant has used tanning booths within 4 weeks prior to Day 1, has had excessive sun exposure, or is not willing to minimize natural and artificial sunlight exposure during the study.
34. Participant has a known or suspected allergy to NDI-034858 or any component of the investigational product, or any other significant drug allergy (such as anaphylaxis or hepatotoxicity).
35. Participant has a known history of clinically significant drug or alcohol abuse in the last year prior to Day 1.
36. For participant consenting to biopsy collection only:

    * Participant has a history of an allergic reaction or significant sensitivity to lidocaine or other local anesthetics.
    * Participant has a history of hypertrophic scarring or keloid formation in scars or suture sites.
    * Participant has taken anticoagulant medication, such as heparin, low molecular weight (LMW)-heparin, warfarin, or antiplatelet agents (except low-dose aspirin ≤ 81 mg which will be allowed), within 2 weeks prior to Day 1, or has a contraindication to skin biopsies. Nonsteroidal anti-inflammatory drugs will not be considered antiplatelet agents and will be allowed.

Primary outcomes:
measure: Percentage of Participants Who Achieved at Least 75 Percent (%) Improvement From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (0) or Almost Clear (1) at Week 12
timeFrame: At Week 12
measure: Percentage of Participants Who Achieved at Least 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI-90) at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants Who Achieved at Least 100% Improvement From Baseline in Psoriasis Area and Severity Index (PASI-100) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Number of Participants With Treatment-emergent Adverse Event (TEAEs) and Serious TEAEs
timeFrame: From start of study drug administration up to Week 16
measure: Plasma Concentrations of NDI-034858 in Participants Receiving Active Treatment
timeFrame: Week 1: Day 1, Pre-dose and 1-hour post-dose; Week 4: Pre-dose, 1-hour and 4 hours post-dose; Week 8: Pre-dose; Week 12: Post-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Nimbus site 137
state: Alabama
city: Birmingham
country: United States
facility: Nimbus site 156
state: Alabama
city: Scottsdale
country: United States
facility: Nimbus site 132
state: Arizona
city: Bryant
country: United States
facility: Nimbus site 133
state: Arkansas
city: Fountain Valley
country: United States
facility: Nimbus site 134
state: California
city: Los Angeles
country: United States
facility: Nimbus site 108
state: California
city: Sacramento
country: United States
facility: Nimbus site 124
state: California
city: San Diego
country: United States
facility: Nimbus site 153
state: California
city: San Diego
country: United States
facility: Nimbus site 111
state: California
city: Santa Rosa
country: United States
facility: Nimbus site 148
state: California
city: Sherman Oaks
country: United States
facility: Nimbus site 120
state: California
city: Doral
country: United States
facility: Nimbus site 155
state: Florida
city: Hialeah
country: United States
facility: Nimbus site 149
state: Florida
city: Largo
country: United States
facility: Nimbus site 130
state: Florida
city: Margate
country: United States
facility: Nimbus site 160
state: Florida
city: Miami Lakes
country: United States
facility: Nimbus site 107
state: Florida
city: Miami Lakes
country: United States
facility: Nimbus site 139
state: Florida
city: Ocala
country: United States
facility: Nimbus site 118
state: Florida
city: Sweetwater
country: United States
facility: Nimbus site 157
state: Florida
city: Tampa
country: United States
facility: Nimbus site 101
state: Florida
city: Tampa
country: United States
facility: Nimbus site 102
state: Florida
city: West Palm Beach
country: United States
facility: Nimbus site 116
state: Florida
city: Columbus
country: United States
facility: Nimbus site 147
state: Georgia
city: Macon
country: United States
facility: Nimbus site 150
state: Georgia
city: Sandy Springs
country: United States
facility: Nimbus site 119
state: Georgia
city: Skokie
country: United States
facility: Nimbus site 123
state: Illinois
city: Clarksville
country: United States
facility: Nimbus site 159
state: Indiana
city: Indianapolis
country: United States
facility: Nimbus site 140
state: Indiana
city: Overland Park
country: United States
facility: Nimbus site 154
state: Kansas
city: Louisville
country: United States
facility: Nimbus site 161
state: Kentucky
city: Louisville
country: United States
facility: Nimbus site 105
state: Kentucky
city: Lake Charles
country: United States
facility: Nimbus site 136
state: Louisiana
city: Metairie
country: United States
facility: Numbus site 114
state: Louisiana
city: Rockville
country: United States
facility: Nimbus site 122
state: Maryland
city: Beverly
country: United States
facility: Nimbus site 115
state: Massachusetts
city: Quincy
country: United States
facility: Nimbus site 135
state: Massachusetts
city: Ann Arbor
country: United States
facility: Nimbus site 146
state: Michigan
city: Bay City
country: United States
facility: Nimbus site 103
state: Michigan
city: Troy
country: United States
facility: Nimbus site 112
state: Michigan
city: Troy
country: United States
facility: Nimbus site 138
state: Michigan
city: New Brighton
country: United States
facility: Nimbus site 158
state: Minnesota
city: New York
country: United States
facility: Nimbus site 143
state: New York
city: Charlotte
country: United States
facility: Nimbus site 129
state: North Carolina
city: Wilmington
country: United States
facility: Nimbus site 106
state: North Carolina
city: Bexley
country: United States
facility: Nimbus site 127
state: Ohio
city: Columbus
country: United States
facility: Nimbus site 145
state: Ohio
city: Fairborn
country: United States
facility: Nimbus site 128
state: Ohio
city: Norman
country: United States
facility: Nimbus site 141
state: Oklahoma
city: Pittsburgh
country: United States
facility: Nimbus site 125
state: Pennsylvania
city: Charleston
country: United States
facility: Nimbus site 110
state: South Carolina
city: Jackson
country: United States
facility: Nimbus site 117
state: Tennessee
city: Nashville
country: United States
facility: Nimbus site 121
state: Tennessee
city: Arlington
country: United States
facility: Nimbus site 109
state: Texas
city: Bellaire
country: United States
facility: Nimbus site 113
state: Texas
city: Katy
country: United States
facility: Nimbus site 131
state: Texas
city: San Antonio
country: United States
facility: Nimbus site 104
state: Texas
city: San Antonio
country: United States
facility: Nimbus site 152
state: Texas
city: Webster
country: United States
facility: Nimbus site 162
state: Texas
city: Spokane
country: United States
facility: Nimbus site 142
state: Washington
city: Calgary
country: Canada
facility: Nimbus site 204
city: Calgary
country: Canada
facility: Nimbus site 206
city: Edmonton
country: Canada
facility: Nimbus site 212
city: Hamilton
country: Canada
facility: Nimbus site 209
city: Markham
country: Canada
facility: Nimbus site 203
city: Montréal
country: Canada
facility: Nimbus site 201
city: Oshawa
country: Canada
facility: Nimbus site 205
city: Peterborough
country: Canada
facility: Nimbus site 210
city: Red Deer
country: Canada
facility: Nimbus site 208
city: Waterloo
country: Canada
facility: Nimbus site 202
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: