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
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Moderate to Severe Plaque Psoriasis
- Sponsor
- Takeda
- Enrollment
- 259
- Locations
- 69
- Primary Endpoint
- Percentage of Participants Who Achieved at Least 75 Percent (%) Improvement From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
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:
- •Male or female participant aged 18 to 70 years, inclusive, at the time of consent.
- •Participant has a history of plaque psoriasis for at least 6 months prior to the screening visit.
- •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).
- •Participant has moderate to severe plaque psoriasis as defined by a PASI score ≥ 12 and a PGA score ≥ 3 at screening and Day
- •Participant has plaque psoriasis covering ≥ 10% of his or her total BSA at screening and Day
- •Participant must be a candidate for phototherapy or systemic therapy.
- •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.
- •Female participants of childbearing potential have had a negative serum pregnancy test at screening and negative urine pregnancy test at Day
- •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.
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:
- •Participant is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.
- •Participant has evidence of erythrodermic, pustular, predominantly guttate psoriasis, or drug induced psoriasis.
- •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.
- •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.
- •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.
- •Participant had a major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study.
- •Participant has a history of Class III or IV congestive heart failure as defined by New York Heart Association Criteria.
- •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
- •Participant has a history of cancer or lymphoproliferative disease within 5 years prior to Day
Arms & Interventions
Placebo
Participants received placebo matched to NDI-034858 oral capsules, once daily (QD) for up to 12 weeks.
Intervention: Placebo
NDI-034858 2 milligrams (mg)
Participants received 2 mg of NDI-034858 oral capsules, QD for up to 12 weeks.
Intervention: NDI-034858 study drug
NDI-034858 5 mg
Participants received 5 mg of NDI-034858 oral capsules, QD for up to 12 weeks.
Intervention: NDI-034858 study drug
NDI-034858 15 mg
Participants received 15 mg of NDI-034858 oral capsules, QD for up to 12 weeks.
Intervention: NDI-034858 study drug
NDI-034858 30 mg
Participants received 30 mg (2\*15 mg) of NDI-034858 oral capsules, QD for up to 12 weeks.
Intervention: NDI-034858 study drug
Outcomes
Primary Outcomes
Percentage of Participants Who Achieved at Least 75 Percent (%) Improvement From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12
Time Frame: Baseline, Week 12
The PASI quantifies the severity of a participant's psoriasis based on both "lesion severity" and the "percent of body surface area (BSA)" affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI composite score varies in increments of 0.1 and range from 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. PASI 75 response is a binary measure defined as at least a 75% improvement in PASI score at Week 12, relative to baseline PASI score.
Secondary Outcomes
- Percentage of Participants Who Achieved at Least 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI-90) at Week 12(Baseline, Week 12)
- Percentage of Participants Who Achieved at Least 100% Improvement From Baseline in Psoriasis Area and Severity Index (PASI-100) at Week 12(Baseline, Week 12)
- Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 12(Baseline, Week 12)
- Percentage of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (0) or Almost Clear (1) at Week 12(At Week 12)
- Number of Participants With Treatment-emergent Adverse Event (TEAEs) and Serious TEAEs(From start of study drug administration up to Week 16)
- Plasma Concentrations of NDI-034858 in Participants Receiving Active Treatment(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)