E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
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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 |
The primary objective is to assess the efficacy and safety of nemolizumab (CD14152) compared to placebo in subjects ≥ 18 years of age with PN after a 16 week treatment period. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the safety, pharmacokinetics, and immunogenicity of nemolizumab (CD14152) compared to placebo. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional skin biopsy, Optional Pharmacogenomic testing and optional Clinical Photography assessment |
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E.3 | Principal inclusion criteria |
1. Male or female and aged ≥18 years at the time of screening;
2. Clinical diagnosis of PN for at least 6 months with:
• Pruriginous nodular lesions on upper limbs, trunk, and/or lower limbs;
• At least 20 nodules on the entire body with a bilateral distribution
• IGA score ≥ 3 (based on the IGA scale ranging from 0 to 4, in which 3
is moderate and 4 is severe) at both the screening and baseline visits
3. Severe pruritus defined as follows on the PP NRS:
• At the screening visit (Visit 1): PP NRS score is ≥ 7.0 for the 24-hour
period immediately preceding the screening visit;
• At the baseline visit (Visit 2): Mean of the daily intensity of the PP NRS
score is ≥ 7.0 over the previous week;
4. Female subjects of childbearing potential (ie, fertile, following
menarche and until becoming post-menopausal unless permanently
sterile) must agree to use at least 1 adequate and approved method of
contraception throughout the study and for 12 weeks after the last study
drug injection. Adequate and approved methods of contraception
applicable for the subject and/or her partner are defined below:
• True abstinence, when in line with the preferred and usual lifestyle of
the subject. Periodic abstinence (eg, calendar, ovulation,
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symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception;
• Progestogen-only oral hormonal contraception;
• Combination of male condom with cap, diaphragm, or sponge with
spermicide (double barrier methods) (*In Germany only, double barrier
methods are not considered a highly effective method of contraception) ;
Note: "Double barrier methods" refers to simultaneous use of a physical
barrier by each partner. Use of a single barrier method (eg, condom)
together with a spermicide is not acceptable.
• Combined (estrogen- and progestogen-containing) oral, intravaginal,
or transdermal hormonal contraception;
• Injectable or implanted hormonal contraception;
• Intrauterine devices or intrauterine hormone-releasing system;
• Bilateral tubal ligation or tube insert (such as the Essure system) at
least 3 months before the study;
• Bilateral vasectomy of male partner at least 3 months before the study
5. Female subjects of non-childbearing potential must meet 1 of the
following criteria:
• Absence of menstrual bleeding for 1 year prior to screening without
any other medical reason, confirmed with follicle stimulating hormone
(FSH) level in the postmenopausal range;
• Documented hysterectomy, bilateral salpingectomy or bilateral
oophorectomy at least 3 months before the study;
6. Subject is willing and able to comply with all of the time commitments
and procedural requirements of the clinical study protocol, including
daily diary recordings by the subject using an electronic handheld device
provided for this study.
7. Read, understood and signed an informed consent form (ICF) before
any investigational procedure(s) are performed. |
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E.4 | Principal exclusion criteria |
1. Body weight < 30 kg;
2. Chronic pruritus resulting from another active condition other than
PN, such as but not limited to scabies, lichen simplex chronicus,
psoriasis, atopic dermatitis, contact dermatitis, acne, folliculitis, lichen
planus, habitual picking/excoriation disorder, sporotrichosis, bullous
autoimmune disease, end-stage renal disease, or cholestatic liver
disease (eg, primary biliary cirrhosis) , or diabetes mellitus or thyroid
disease that is not adequately treated, as per standard of care;
3. Unilateral lesions of prurigo (eg, only one arm affected);
4. History of or current confounding skin condition (eg, Netherton
syndrome, cutaneous T-cell lymphoma [mycosis fungoides or Sezary
syndrome], chronic actinic dermatitis, dermatitis herpetiformis)
5. Subjects meeting 1 or more of the following criteria at screening or
baseline:
- Had an exacerbation of asthma requiring hospitalization in the
preceding 12 months;
- Reporting asthma that has not been well-controlled (ie, symptoms
occurring on > 2 days per week, nighttime awakenings 2 or more times
per week, or some interference with normal activities) during the
preceding 3 months;
- Asthma Control Test (ACT) ≤ 19 (only for subjects with a history of
asthma)
- Peak expiratory flow (PEF) < 80% of the predicted value.
6. Subjects with a current medical history of chronic obstructive
pulmonary disease and/or chronic bronchitis;
7. Cutaneous infection within 1 week before the baseline visit or any
infection requiring treatment with oral or parenteral antibiotics,
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antivirals, antiparasitics, or antifungals within 2 weeks before the
baseline visit, or any confirmed or suspected coronavirus disease
(COVID)-19 infection within 2 weeks. Subjects may be rescreened once
the infection has resolved. Resolution of COVID-19 infection can be
confirmed by recovery assessment methods, as described in Section
8.4.2;
8. Positive serology results (hepatitis B surface antigen [HBsAg] or
hepatitis B core antibody [HBcAb], hepatitis C [HCV] antibody with
positive confirmatory test for HCV [eg, polymerase chain reaction
(PCR)], or human immunodeficiency virus antibody) at the screening
visit;
9. Requiring rescue therapy for PN during the screening period or
expected to require rescue therapy within 4 weeks following the
baseline visit;
10. Subjects with active atopic dermatitis (signs and symptoms other
than dry skin) in the last 3 months;
11. Neuropathic and psychogenic pruritus such as but not limited to
notalgia paresthetica, brachioradial pruritus, small fiber neuropathy,
skin picking syndrome, or delusional parasitosis;
12. Having received any of the treatments in the table reported in the
protocol within the specified timeframe before the baseline visit;
13. Previous participation in a clinical study with nemolizumab;
14. Pregnant women (positive serum pregnancy test result at the
screening visit or positive urine pregnancy test at the baseline visit),
breastfeeding women, or women planning a pregnancy during the
clinical study;
15. History of lymphoproliferative disease or history of malignancy of
any organ system within the last 5 years, except for:
- Basal cell carcinoma, squamous cell carcinoma in situ (Bowen's
disease), or carcinomas in situ of the cervix that have been treated and
have no evidence of recurrence in the last 12 weeks before the screening
visit, or;
- Actinic keratoses that have been treated
16. History of hypersensitivity (including anaphylaxis) to an
immunoglobulin product (plasma-derived or recombinant, eg,
monoclonal antibody) or to any of the study drug excipients;
17. Current active or latent tuberculosis (TB) infection or history of
either untreated or inadequately treated active or latent TB according to
the local applicable guidelines;
18. Known or suspected immunosuppression or unusually frequent,
recurrent, severe, or prolonged infections as per investigator judgment;
19. Any medical or psychological condition or any clinically relevant
laboratory abnormalities, such as but not limited to elevated alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) (> 3 ×
upper limit of normal [ULN]) in combination with elevated bilirubin (> 2
× ULN), during the screening period that may put the subject at
significant risk according to the investigator's judgment, if he/she
participates in the clinical study, or may interfere with study
assessments (eg, poor venous access or needle-phobia);
20. History of alcohol or substance abuse within 6 months of the
screening visit;
21. Planned or expected major surgical procedure during the clinical
study;
22. Subject is unwilling to refrain from using prohibited medications
during the clinical study;
See the full list of exclusion criteria in the protocol Section 8.2 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Proportion of subjects with an improvement of = 4 from baseline in Peak Pruritus Numeric Rating Scale (PP NRS) at Week 16.
- Proportion of subjects with an Investigator Global Assessment (IGA) success (defined as an IGA of 0 [Clear] or 1 [Almost clear] and a = 2-point improvement from baseline) at Week 16;
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Key Secondary Efficacy Endpoints:
- Proportion of subjects with an improvement of ≥ 4 from baseline in PP NRS at Week 4;
- Proportion of subjects with PP NRS < 2 at Week 16.
- Proportion of subjects with an improvement of = 4 from baseline in SD NRS at Week 16;
- Proportion of subjects with an improvement of = 4 from baseline in SD NRS at Week 4;
- Proportion of subjects with PP NRS < 2 at Week 4
Secondary Efficacy Endpoints:
- IGA success rate at each visit through Week 16;
- IGA score at each visit through Week 16;
- Percentage of pruriginous lesions with excoriations/crusts (Prurigo
Activity Score [PAS] item 5a) at each visit through Week 16;
- Percentage of healed prurigo lesions (PAS item 5b) at each visit
through Week 16;
- Change from baseline in number of lesions in representative area (PAS
item 4) at each visit through Week 16;
- Proportion of subjects with an improvement of ≥ 4 from baseline in PP
NRS through Week 16;
- Proportion of subjects with PP NRS < 2 from baseline through Week
16;
- Proportion of subjects with PP NRS < 3 from baseline through Week
16;
- Absolute change from baseline in PP NRS through Week 16;
- Percent change from baseline in PP NRS through Week 16;
- Proportion of subjects with an improvement of ≥ 4 from baseline in AP
NRS through Week 16;
- Proportion of subjects with AP NRS < 2 from baseline through Week
16;
- Absolute change from baseline in AP NRS through Week 16;
- Percent change from baseline in AP NRS through Week 16;
- Proportion of subjects with an improvement of ≥ 4 from baseline in SD
NRS through Week 16;
- Absolute change from baseline in SD NRS through Week 16;
- Percent change from baseline in SD NRS through Week 16;
- Change from baseline in sleep diary endpoints (sleep onset latency,
wakefulness after sleep onset [WASO], total awake time, total sleep
time, sleep efficiency, WASO related to PN, number of WASO related to
PN) based on recordings from subject sleep diary through Week 16;
- Change from baseline in PN-associated pain frequency through Week
16;
- Change from baseline in PN-associated pain intensity through Week 16;
- Proportion of subjects reporting low disease activity (clear, almost
clear, or mild) based on Patient Global Assessment of Disease (PGAD) at
Week 16;
- Proportion of subjects satisfied with study treatment (good, very good,
or excellent) based on Patient Global Assessment of Treatment (PGAT)
at Week 16;
- Proportion of subjects with an improvement of ≥ 4 in DLQI through Week 16;
- Change from baseline in DLQI through Week 16
- Change from baseline in Hospital Anxiety and Depression Scale (HADS) for each subscale (ie, depression and anxiety) at Week 16;
- Change from baseline in EuroQoL 5-Dimension (EQ-5D) at Week 16;
Safety Endpoints:
- The safety endpoints of this study are the incidence and severity of
AEs, including TEAEs, AESIs, and SAEs. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As specified within the list of endpoints |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, quality of life |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 2 |
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 | 39 |
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 |
Canada |
United States |
Belgium |
France |
Netherlands |
Poland |
Spain |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 7 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 7 |