A Study to Find Out if TEV-45779 Helps to Treat Chronic Idiopathic Urticaria/Chronic Spontaneous Urticaria That is Not Helped by Antihistamines
Scientific Title of Study
A Multinational, Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of TEV-45779 Compared to Omalizumab (XOLAIR®) in Patients With Chronic Idiopathic Urticaria/Chronic Spontaneous Urticaria who Remain Symptomatic Despite Antihistamine (H1) Treatment
Amrita Institute of Medical Sciences and Research Centre
Dept of Dermatology,
AIMS Ponekkara P.O
Kochi, Kerala, India-682041 Ernakulam KERALA
9847179964
vinithavpanicker@aims.amrita.edu
Dr Vartak Suneel Chandrakant
Assured Care Plus Hospital
Department of Dermatology
4th & 5 th Floor Star Plus Complex, Lam Road, Opposite to NMC Divisional Office,
Near Muktidham Temple, Nashik Road, Nashik, Maharashtra 422101 India Nashik MAHARASHTRA
9373901829
suneel.vartak@gmail.com
Dr Godse Kiran Vasant
D.Y Patil Medical College and Research Centre
Department of Dermatology
Sector -5,Nerul, Navi Mumbai, Thane, Maharashtra- 400706 India Thane MAHARASHTRA
9322266687
drgodse@gmail.com
Dr Roshni A Vahora
GMERS Medical College and General Hospital
Department of Dermatology
Gotri Road, Gotri, Vadodara-390021, Gujarat, India Vadodara GUJARAT
9328162974
dr.roshnivahora@gmail.com
Dr Krina Patel
GMERS Medical College, Civil Hospital - Sola
Department of Dermatology
SG Highway, near Gujarat High Court, Sola, Ahmedabad, Gujarat 380060 India Ahmadabad GUJARAT
9227222221
drkbpatel66@gmail.com
Dr Nandini AS
Kempegowda Institute of Medical Sciences (KIMS Hospital
Department of Dermatology B Block, 2nd floor, Room no 10, K R Road, V V Puram, Bangalore 560004 Bangalore KARNATAKA
9886829579
drnandinishiva@gmail.com
Dr Shivakumar Patil
KLES Dr. Prabhakar Kore Hospital and MRC
Nehru Nagar, Belagavi-590010 Karnataka, India Belgaum KARNATAKA
8312473099
shivakumarkpatil@gmail.com
Dr T K Sumathy
M S Ramaiah Medical College and Hospitals
Department of Dermatology, M S Ramaiah Nagar, MSRIT Post, Bengaluru 560054, Karnataka, India. Bangalore KARNATAKA
8040502983
tksumathy@gmail.com
Dr Dipak A Patel
Nirmal Hospital Pvt Ltd
Ring Road, Surat - 395002, Gujarat, India Surat GUJARAT
9377113143
drdipakapatel@gmail.com
Dr Rohit Batra
Sir Ganga Ram Hospital
Department of Dermatology
Sir Ganga Ram Hospital Marg, Rajendra Nagar, New Delhi -110060 India Central DELHI
Yash Societys Sujata Birla Hospital Ethics Committee, 1st Floor, Sujata Birla Hospital & Medical Research Center, Opposite to Bytco College, Nashik Pune Highway, Nashik Road, Nashik 422101, Maharashtra, India
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: L501||Idiopathic urticaria,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo to complement TEV-45779 or XOLAIR
Placebo (no active) to complement TEV-45779 (omalizumab) or XOLAIR (omalizumab) is supplied as a single dose PFS. Each PFS of placebo contains 1 mL solution of the same composition as the TEV-45779 (omalizumab) and XOLAIR (omalizumab) syringes, but without active drug substance. Placebo syringes are only required as a complementary injection to the 150 mg doses of TEV-45779 or XOLAIR in order to administer 2 injections per dosing in all groups and, thereby, maintain the blinding of patients and investigators regarding the strength of the dose. In addition to the study treatment second generation H1-antihistamine will be provided as standard of care (SoC) to the patients.
Intervention
TEV-45779 (Omalizumab)
150mg/ml or 300 mg/ml Solution for injection in pre-filled
syringe
TEV-45779 (proposed biosimilar to omalizumab) is provided as a sterile, preservative-free, clear to slightly opalescent and colorless to pale brownish-yellow solution intended for subcutaneous injection. Patients will receive a total of 6 treatments, each consisting of 2 subcutaneous injections resulting in 150mg/ml or 300mg/ml of TEV-45779 as add-on therapy every 4 weeks. Patients will receive 3 treatments in the main treatment period at week 0, 4, 8 and 3 treatments in the transition period at week 12, 16, 20. The total duration of the study is up to 43 weeks. In addition to the study treatment second generation H1-antihistamine will be provided as standard of care (SoC) to the patients.
Comparator Agent
XOLAIR (Omalizumab) Injection
150mg/ml or 300 mg/ml
XOLAIR (omalizumab) injection is supplied as a single dose PFS. Each PFS of XOLAIR contains 150 mg of omalizumab in 1 mL of solution. Patients will receive a total of 6 treatments, each consisting of 2 subcutaneous injections resulting in 150mg/ml or 300mg/ml of XOLAIR as add-on therapy every 4 weeks. Patients will receive 3 treatments in the main treatment period at week 0, 4, 8 and 3 treatments in the transition period at week 12, 16, 20. The total duration of the study is up to 43 weeks. In addition to the study treatment second generation H1-antihistamine will be provided as standard of care (SoC) to the patients.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
Diagnosis of CIU refractory to H1 antihistamines for ≥3 months.
ExclusionCriteria
Details
• Chronic urticaria with clearly defined underlying etiology
• Other skin disease associated with itch
• Evidence of parasitic infection on stool evaluation for ova and parasites
• History of anaphylactic shock
• Hypersensitivity to omalizumab or any component of the formulation
• Required background therapy with other than protocol-defined antihistamines
• Any medical condition that could jeopardize or would compromise the patient safety or ability to participate in this study
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
1) Change from baseline in the ISS7 at Week 12 between TEV 45779 300 mg and XOLAIR 300 mg (ISS 7 is a weekly itch severity score calculated as sum of the daily itch severity score for 7 days, on a scale of 0 to 3)
2) Relative potency of TEV 45779 and XOLAIR (Relative potency TEV45779 to the Xolair defined as the dose of TEV45779 that produces the same biological response as one unit of the dose of the Xolair. The relative potency and its CI will be measured by change in ISS7 at Week 12 using a 4 point assay based on the 300 mg and 150 mg dose levels of each product)
1) Time Frame: Baseline and week 12
2) Time Frame: Baseline and week 12
Secondary Outcome
Outcome
TimePoints
Change from baseline in the ISS7 at Week 12 (ISS 7 is a weekly itch severity score calculated as sum of the daily itch severity score for 7 days, on a scale of 0 to 3)
Time Frame: Baseline, week 4 and week 12
Change from baseline in the UAS7 at Week 12 (Change from baseline in the Urticaria Activity Score (UAS) - sum of the daily number of wheals score and itch severity score over 7 days, range from 0 (minimum) to 6 (maximum)) at Week 12)
Time Frame: Baseline and week 12
Percentage of patients with a UAS7 ≤6 at Week 12 (Percentage of patients with a weekly Urticaria Activity Score ≤6 at Week 12)
Time Frame: week 12
Percentage of complete responders with weekly Urticaria Activity Score(UAS7) 0
Time Frame: week 12
Change from baseline in the physicians (in-clinic) assessment of weekly Urticaria Activity Score at Week 12.
Time Frame: Baseline and week 12
Change from baseline in the weekly number of wheals score at Week 12
Time Frame: Baseline and week 12
Change from baseline in the weekly size of the largest wheals score at Week 12
Time Frame: Baseline and week 12
Time to minimally important difference (MID) defined as a reduction from baseline in ISS7 of ≥5 points) response in ISS7 score by Week 12
Time Frame: Baseline till week 12
Percentage of ISS7 MID responders at Week 12 (Percentage of patients with minimally important difference defined as reduction of ≥5 points from baseline in ISS7 at Week 12)
Time Frame: Baseline and week 12
Percentage of angioedema-free days from Week 4 to Week 12
Time Frame: week 4 and week 12
Change from baseline in the overall DLQI score at Week 12 (Change from baseline in the overall dermatology life quality index (DLQI) score at Week 12; comparisons of TEV 45779 and XOLAIR treatment arms. The DLQI consists of 10 questions concerning patients perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week. The DLQI is calculated by adding the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired)
Time Frame: Baseline and week 12
Change from Week 12 in ISS7 at Week 24
Time Frame: week 12 and week 24
Change from Week 12 in ISS7 at Week 40
Time Frame: week 12 and week 40
Change from Week 12 in the UAS7 (sum of the daily number of wheals score and itch severity score over 7 days) at Week 24
Time Frame: week 12 and week 24
Change from Week 12 in the physicians (in-clinic) assessment of UAS7 at Week 24
Time Frame: week 12 and week 24
Change from Week 12 in the weekly number of wheals score at Week 24
Time Frame: week 12 and week 24
Change from Week 12 in the weekly number of wheals score at Week 40
Time Frame: week 12 and week 40
Change from Week 12 in the weekly number of the largest wheals score at Week 24
Time Frame: week 12 and week 24
Change from Week 12 in the weekly number of the largest wheals score at Week 40
Time Frame: week 12 and week 40
Percentage of angioedema-free days from Week 12 to Week 24
Time Frame: week 12 and week 24
Change from Week 12 in the overall DLQI score at Week 24 (Change from Week 12 in the overall dermatology life quality index (DLQI) score at Week 24)
Time Frame: week 12 and week 24
Change from Week 12 in the overall DLQI score at Week 40 (Change from Week 12 in the overall dermatology life quality index (DLQI) score at Week 40)
Time Frame: week 12 and week 40
Incidence of adverse event and withdrawals due to adverse events in the main period (Number of patients reporting at least one treatment-emergent adverse event up to week 12)
Time Frame: Baseline till week 12
Incidence of adverse event in the transition and follow up period (Number of patients reporting at least one treatment-emergent adverse event from week 12 till week 40)
Time Frame: week 12 till week 40
Incidence of antidrug antibodies (ADAs) in the main treatment period (Number of patients with confirmed positive antidrug antibodies (ADAs) post-baseline up to week 12)
Time Frame: Baseline till week 12
Incidence of antidrug antibodies (ADAs) in the transition and follow up period (Number of patients with confirmed positive antidrug antibodies (ADAs) post-week 12 up to week 40)
Time Frame: week 12 till week 40
Target Sample Size
Total Sample Size="600" Sample Size from India="100" Final Enrollment numbers achieved (Total)= "608" Final Enrollment numbers achieved (India)="52"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a multicenter, randomized, double-blind study to demonstrate similar efficacy and safety of TEV-45779 compared to XOLAIR administered sc at doses of 300 mg or 150 mg every 4 weeks for 24 weeks (6 treatments) in patients with Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) who remain symptomatic despite antihistamine (H1) treatment. This study will consist of a screening period (up to 2 weeks), a 24-week treatment period consisting of a 12-week double-blind main treatment period and a 12-week double-blind transition period, which is followed by a 16-week follow-up period. The total duration of the study is up to 43 weeks.
At baseline, patients will be randomized in a 2:2:1:1 ratio to receive the first 3 treatments of TEV-45779 300 mg, XOLAIR 300 mg, TEV-45779 150 mg or XOLAIR 150 mg (main treatment period). At Week 12, prior to receiving their fourth dose of study medication, patients in the XOLAIR 300 mg and the XOLAIR 150 mg treatment groups will be randomized 1:1 to receive 3 additional doses of XOLAIR (at the same dose level as prior to randomization, or switch to 3 doses of TEV-45779 (transition period) at the same dose level as prior to randomization. All patients in the TEV-45779 groups will continue to receive TEV-45779 at the same dose levels.