E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pruritus in Subjects with Prurigo Nodularis |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic itchy skin in subjects with Prurigo Nodularis, a skin condition that causes hard, itchy lumps (nodules) to form on the skin. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037084 |
E.1.2 | Term | Prurigo nodularis |
E.1.2 | System Organ Class | 100000004858 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of subcutaneous (SC) KPL-716 vs. placebo in reducing pruritus in PN subjects experiencing severe pruritus |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of SC KPL-716 vs. placebo in improving sleep in PN subjects experiencing severe pruritus • To evaluate the effect of SC KPL-716 vs. placebo in improving quality of life in PN subjects experiencing severe pruritus • To evaluate the effect of SC KPL-716 vs. placebo in reducing disease severity in PN subjects experiencing severe pruritus • To evaluate the safety and tolerability of SC KPL-716 vs. placebo in PN subjects experiencing severe pruritus • To evaluate the pharmacokinetics (PK) of SC KPL-716 in PN subjects experiencing severe pruritus |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female aged 18 to 80 years, inclusive, at the time of consent. 2. Have a physician-documented diagnosis of PN that is confirmed by review of medical photography (as outlined in the Study Manual) during the Screening Period. Duration of PN (since the time of first PN nodule) must be at least 6 months from the time of first PN nodule to Day 1, as affirmed by the subject. 3. Have at least 20 nodules of approximately 0.5 to 2 cm at the Screening Visit and Day 1. The nodules must be pruritic and present on at least 2 different anatomical locations (not be localized), involve the extremities, with extensor extremity involvement greater than the flexor extremity involvement. Nodules on the head (face and scalp) are not counted as an anatomical location for eligibility criteria. Each arm, each leg, and trunk are considered different anatomical locations. 4. Subject has severe pruritus, defined as WI-NRS ≥7 at the Screening Visit and a mean weekly WI-NRS ≥7 for the week (7 consecutive days) immediately prior to randomization (at least 5 days of recordings) on eDiary. 5. PN-IGA score of ≥3 (on a scale of 0-4, in which 3 is moderate and 4 is severe) at Screening and Baseline Visits 6. Sexually active female subjects must be: • postmenopausal, defined as at least 12 consecutive months post cessation of menses (without an alternative medical cause) and confirmed by a follicular stimulating hormone (FSH) test, or • surgically sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy or • nonpregnant, nonlactating, and having agreed to use a highly effective method of contraception from the Screening Visit until 16 weeks after final study drug administration. Note: highly effective methods of contraception include: ▪ hormonal contraceptives associated with inhibition of ovulation (stable dose for at least 4 weeks prior to first dose) ▪ intrauterine device ▪ intrauterine system ▪ bilateral tubal ligation ▪ vasectomized male partner ▪ abstinence from heterosexual intercourse 7. Sexually active male subjects must have documented vasectomy or must agree to use a condom or highly effective method of contraception as defined above with their partners of childbearing potential from first dose until 16 weeks after final study drug administration. 8. Male subjects must agree to refrain from donating sperm from first dose until 16 weeks after the last study drug administration. Female subjects must agree to refrain from donating eggs from first dose until 16 weeks after the last study drug administration. 9. Female of childbearing potential must have a negative serum β-hCG test at the Screening Visit and negative urine pregnancy test on Day 1. 10. Able to comprehend and willing to sign an Informed Consent Form and able to abide by the study restrictions and comply with all study procedures for the duration of the study. 11. Subjects must be on optimized and stable treatment for co-morbidities for at least 28 days prior to Day 1. |
|
E.4 | Principal exclusion criteria |
1. Use of the following medications within the indicated timeframe prior to Day 1 and does not agree to refrain from the use of the medications throughout the study (except those specified in the Pharmacy Manual): a. Systemic corticosteroids (IV/IM/oral): 4 weeks; Note: Intranasal corticosteroids, eye drops containing corticosteroids, and inhaled corticosteroids for stable medical conditions are allowed. b. Intralesional corticosteroids and intra-articular corticosteroids: 6 weeks c. Topical treatments for PN including but not limited to corticosteroids, calcineurin inhibitors, phosphodiesterase inhibitors, retinoids, calcipotriol, capsaicin, camphor, polidocanol, cannabinoids, gabapentin, or tars: 2 weeks d. Antihistamines: 2 weeks e. Immunomodulators (for example, cyclosporin, methotrexate, retinoids, azathioprine, mycophenolate, and thalidomide): 4 weeks f. Neuroactive drugs such as gabapentin and pregabalin: 4 weeks g. Cannabinoids: 2 weeks h. Opioid antagonists or agonists: 5 half-lives if known or 4 weeks i. Janus kinase inhibitors: 5 half-lives if known or 4 weeks j. Dupilumab: 8 weeks k. Any other marketed biologic: 5 half-lives or within 4 months of using rituximab l. Any investigational drug: 5 half-lives m. Phototherapy involving UVA, UVB, or excimer: 4 weeks n. Tanning salon use: 4 weeks o. Live attenuated vaccine: 12 weeks 2. Has received any investigational biologic or non-biologic drug that targets Oncostatin M, IL-31, IL-31 receptor α, or Oncostatin M receptor β in the past 3 months. 3. Required rescue therapy for PN during the Screening Period or expected to require rescue therapy within 4 weeks following the Baseline Visit. 4. Has a significant exacerbation and/or skin eruption during the Screening Period (prior to the study drug administration) that requires medical intervention. 5. Presence of scabies, insect bite, lichen simplex chronicus, psoriasis, acne, folliculitis, habitual picking, lymphomatoid papulosis, chronic actinic dermatitis, dermatitis herpetiformis, sporotrichosis, bullous disease, and/or skin condition other than PN or atopic dermatitis unless approved by the Sponsor. 6. Plan to change emollients or moisturizers, or to have bath oil treatment for relief of pruritus during the course of the trial. 7. Presence of psychogenic pruritus or neuropathic pruritus at the Screening Visit. 8. Presence of severe depression as indicated by PHQ-9 total score of ≥20 or item 9 score >0 at the Screening Visit or Day 1. 9. Presence of severe anxiety as indicated by GAD-7 score of ≥15 at the Screening Visit or Day 1. 10. Presence of severe chronic pain (e.g., back pain, migraine, osteoarthritis, etc., defined as ≥7.0 on 0 to 10 NRS scale with 0 being no pain and 10 being the worst pain possible) at the Screening Visit. 11. Presence of uncontrolled hyperthyroidism or hypothyroidism or uncontrolled diabetes defined as hemoglobin A1c >7.5%. 12. Presence or history of cancer or lymphoproliferative disease within 5 years prior to the Screening Visit, with the exception of basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix successfully treated and considered controlled. 13. Presence or history of immune deficiency, or opportunistic infections. 14. Positive results for hepatitis B surface antigen (HbsAg) and/or hepatitis B anti-core antibody (anti-HBc) but negative results for anti-surface antibody (anti-HBs) at the Screening Visit. 15. Positive results for hepatitis C antibody unless patient received curative therapy and a negative viral load is documented. 16. Human immunodeficiency virus (HIV) infection or positive HIV serology at the Screening Visit. 17. Positive COVID-19 viral test at the Screening Visit or suspected COVID-19 infection at the Baseline Visit. 18. Subject is on hemodialysis or peritoneal dialysis. 19. Latent or active TB, as determined by a positive Quantiferon-based TB test result at the Screening visit. 20. Laboratory abnormalities that fall outside the windows below at the Screening Visit (see Protocol). 21. Major surgery within 12 weeks prior to Day 1 or has a major surgery planned during the study. 22. Has an active infection, including skin infection, requiring systemic treatment within 4 weeks and/or topical treatment within 2 weeks of Day 1. Subject has an active or chronic parasitic infection.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in weekly average Worst Itch–Numeric Rating Scale (WI-NRS) at Week 16 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 16 (end of double-blind period). |
|
E.5.2 | Secondary end point(s) |
• Proportion of subjects achieving at least a 6-point reduction from baseline in weekly average WI-NRS at Week 16 • Proportion of subjects achieving at least a 4-point reduction from baseline in weekly average WI-NRS at Week 16 • Proportion of subjects achieving 0 or 1 in PN-IGA at Week 16 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 16 (end of double-blind period). |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Immunogenicity |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Korea, Republic of |
Taiwan |
United States |
Austria |
France |
Poland |
Czechia |
Germany |
Italy |
Belgium |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |