24 weeks double-blind randomized placebo-controlled trial to evaluate efficacy, PK, safety of LOU064 in adolescents (12 - <18) with CSU and inadequate response to H1-antihistamine followed by optional 3 years open-label extension and an optional 3 years safety long-term treatment-free follow-up

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

6 Dec 2023 → ongoing

Decision date (initial)

2023-09-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Others, Efficacy

To assess the efficacy of remibrutinib versus placebo in CSU with respect to absolute change from baseline in UAS7, ISS7 and HSS7 at Week 12

Secondary objectives 7

1. To assess pharmacokinetic parameters at Week 12
2. To assess the proportion of participants achieving disease activity control (UAS7 ≤ 6) at Week 12 and over time who are treated with remibrutinib compared to placebo-treated participants
3. To assess the proportion of participants achieving complete absence of hives and itch (UAS7 = 0) at Week 12 and over time who are treated with remibrutinib compared to placebo-treated participants
4. To evaluate the efficacy of remibrutinib versus placebo in CSU with respect to change from baseline in CDLQI score at Week 12
5. To evaluate the efficacy of remibrutinib versus placebo with respect to cumulative number of weeks between baseline and Week 12 during which subjects achieve Angioedema Activity Score Over 7 Days equal to 0 (AAS7 = 0)
6. To assess the safety and tolerability of remibrutinib over 24 weeks
7. To assess the safety and tolerability of long-term treatment with remibrutinib in the OLE period

Conditions and MedDRA coding

Chronic Spontaneous Urticaria

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002582-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male and female adolescent participants aged ≥ 12 to < 18 years of age at the time of signing the informed consent.
2. CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation)
3. Diagnosis of CSU inadequately controlled by second-generation H1-AH at the time of randomization defined as: - The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite the use of second-generation H1-AH during this time period according to local treatment guidelines - UAS7 score (range 0 - 42) ≥ 16, ISS7 score (range 0 - 21) ≥ 6 and HSS7 score (range 0 - 21) ≥ 6 during the 7 days prior to randomization (Day 1)
4. Documentation of hives within three months before randomization (either at screening and/or at randomization; or documented in the participants’ medical history)

Exclusion criteria 10

1. Previous use of remibrutinib or other BTK inhibitors
2. Significant bleeding risk or coagulation disorders.
3. History of gastrointestinal bleeding.
4. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
5. History or current hepatic disease.
6. Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant.
7. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
8. Participants 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
9. Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary angioedema, or drug-induced urticaria
10. Any other skin disease associated with chronic itching that might influence in the investigator’s opinion the study evaluations and results, e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change from baseline in ISS7, HSS7, UAS7 at week 12

Secondary endpoints 8

1. Concentration of remibrutinib at Week 12 including Cmax, Tmax and AUC
2. Absolute change from baseline in UAS7 at Week 12
3. Achievement of UAS7 ≤ 6 (yes/no) at Week 12 and over time
4. Achievement of UAS7 = 0 (yes/no) at Week 12 and over time
5. Absolute change from baseline in CDLQI score at Week 12
6. Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response between baseline and Week 12
7. Occurrence of treatment emergent AEs, SAEs and laboratory and vital signs abnormalities during the core period
8. Occurrence of treatment-emergent adverse events, serious adverse events and laboratory and vital signs abnormalities during the OLE period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 17

Locations

5 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

5 submissions — initial application plus substantial / non-substantial modifications