E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Spontaneous Urticaria |
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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 | PT |
E.1.2 | Classification code | 10072757 |
E.1.2 | Term | Chronic spontaneous urticaria |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 |
To assess the long-term safety and tolerability of LOU064 in patients with CSU who have participated in CLOU064A2201 |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of LOU064 when given without H1-antihistamines in patients with CSU who have participated in CLOU064A2201 with respect to change from baseline in UAS7, achieving controlled disease (defined by a UAS7≤6), and achieving complete response (defined by a UAS7=0) at Week 4 of treatment
- To evaluate the long-term efficacy of LOU064 in patients with CSU who have participated in CLOU064A2201 with respect to maintaining or achieving controlled disease (defined by a UAS7≤6) over time
- To evaluate the long-term efficacy of LOU064 in patients with CSU who have participated in CLOU064A2201 with respect to change from baseline in UAS7 over time |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written informed consent must be obtained before any assessment is performed.
- Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules.
- Subjects must have completed the Week 12 visit (end of treatment period) or the Week 16 visit (end of the follow-up period) of CLOU064A2201 and will be allocated to the treatment period or the observational period of CLOU064A2201E1 based on the UAS7 score (of the 7 days prior to the respective visit) as follows:
a) Subjects rolling over at Week 12 of CLOU064A2201 with a UAS7≥16 will be allocated to the Treatment period (note: subjects with UAS7<16 at Week 12 are not eligible to rollover into CLOU064A2201E1 but need to enter the follow-up period of CLOU064A2201).
b) Subjects rolling over at Week 16 of CLOU064A2201 with a UAS7≥16 will be allocated to the Treatment period.
c) Subjects rolling over at Week 16 of CLOU064A2201 with a UAS7<16 will be allocated to the Observational period.
- Rollover criteria for subjects with CSU from other, not-yet specified studies with LOU064 will be detailed in the protocols of these studies. |
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E.4 | Principal exclusion criteria |
- Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days (for small molecules) prior to enrollment or until the expected pharmacodynamic (PD) effect has returned to baseline (for biologics), whichever is longer; or longer if required by local regulations.
- History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
- Subjects having a clearly defined, predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact urticaria
- Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or acquired/drug-induced urticaria
- Any other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results, eg atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
- History or current diagnosis of ECG abnormalities indicating significant risk of safety for subjects participating in the study
- Patients/subjects taking medications prohibited by the protocol
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 7 days after stopping study medication.
- Major surgery within 8 weeks prior to enrollment or surgery planned prior to end of the treatment period.
- History of live attenuated vaccine within 6 weeks prior to enrollment or requirement to receive these vaccinations at any time during study drug treatment
- Evidence of clinically significant cardiac, neurologic, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders or gastrointestinal disease that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participant participation.
- Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
- Hematology parameters at last visit before Day 1 of the Treatment period (either last available value from CLOU064A2201 or most recent value taken during observational period): Hemoglobin: < 10 g/dl; Platelets: < 100 000/mm3; White blood cells: < 3 000/mm3; Neutrophils: < 1 500/mm3;
- Significant bleeding risk or coagulation disorders
- History of gastrointestinal bleeding, eg in association with use of Nonsteroidal Anti-Inflammatory Drug (NSAID)
- Requirement for anti-platelet or anticoagulant medication (for example, warfarin, or clopidogrel or Novel Oral Anti-Coagulant - NOAC) other than acetylsalicylic acid (up to 100 mg/d)
- History or presence of thrombotic or thromboembolic event, or increased risk for thrombotic or thromboembolic event
- History or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) at last visit before Day 1 of the Treatment period (either last available value from CLOU064A2201 or most recent value taken during observational period)
- History of renal disease or creatinine level above 1.5x ULN at last visit before Day 1 of the Treatment period (either last available value from CLOU064A2201 or most recent value taken during observational period)
- Known or suspected history of an ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (eg tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis), HIV, Hepatitis B/C |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints will include but not be limited to: occurrence of treatment emergent (serious and non-serious) adverse events during the extension study |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
56 weeks (treatment plus follow-up period) |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in UAS7 at Week 4
2. UAS7≤6 response at Week 4
3. UAS7=0 response at Week 4
4. UAS7≤ 6 response over time
5. Change from baseline in UAS7 over time |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Effect of LOU064 on disease-related 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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Japan |
Russian Federation |
United States |
Belgium |
Denmark |
France |
Germany |
Hungary |
Netherlands |
Poland |
Slovakia |
Spain |
United Kingdom |
Czechia |
Argentina |
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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
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Study completion is defined as when the last subject finishes their Study Completion visit, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the investigator, or in the event of an early study termination decision, the date of that decision |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 12 |