Approval Probability
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Label indication XOLAIR is an anti-IgE antibody indicated for: Moderate to severe persistent asthma in adults and pediatric patients 6 years of age and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids ( 1.1 ) Chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients 18 years of age and older with inadequate response… FDA label
Also known as Omalizumab, Xolair
IGE025 · 23 trials · 14 indications
Nasal symptoms (sneezing, rhinorrhea and nasal congestion) were recorded by the patient everyday in their e-Diary, on a scale of 0 (none) to 4 (intense/severe). Nasal symptom score (0-12 point) consisted of score for severity of sneezing (0-4 point), rhinorrhea (0-4 point) and nasal congestion (0-4 point). Severe symptom period: The three weeks where the cumulative value of the mean daily nasal symptom score is the maximum. The three weeks must also meet one of the following criteria: 2) ≥ 70% of the period with concomitant use of fluticasone propionate is included in this three weeks. 2) ≥ 70% of this three weeks includes the period with concomitant use of fluticasone propionate. If not, severe symptom period was extended at a minimum to meet one of the criteria above. The severe symptom period will be defined as: the three weeks where the cumulative value of the mean daily nasal symptom score will be the maximum.
The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None 1. = Mild (minimal awareness, easily tolerated) 2. = Moderate (definite awareness, bothersome but tolerable) 3. = Severe (difficult to tolerate)
The weekly itch severity score is a component of the Urticaria Activity Score 7 (UAS7) composite score. The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score from baseline indicates improvement.
The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from the last 7 days of the second dosing period.
The CU-Q2oL is a questionnaire that measures the relative burden of chronic urticaria on subjective well-being. It consists of 23 questions in 3 domains (symptoms, general impairment, difficulties and problems due to urticaria). Participants are asked to respond how much they are troubled by each problem on a 5-point Likert scale (1= not at all to 5= very much). An overall score is calculated and normalized to a scale of 1 to 100.
A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates.
Venous blood samples were collected at screening and at Week 16. Flow cytometry analysis determined the FcεRI receptors expression of blood basophils (mean fluorescence intensity(MFI)). Relative change in mean fluorescence intensity at the end of study was expressed as a percentage of baseline value.
Venous blood samples were collected at screening and at Week 16. Flow cytometry analysis determined the FcεRI receptors expression of dendritic cells (mean fluorescence intensity (MFI)). Relative change in mean fluorescence intensity at the end of study was expressed as a percentage of baseline value.
An assessment of the immunogenic potential of omalizumab liquid was a primary objective of the study, and was based on the results of the human anti-human antibody (HAHA) assays at the end of the follow-up period. A participant was considered potentially HAHA positive if either Fab or Fc was more than 2.0 titer. All values more than 2.0 titer were re-assayed to obtain a confirmatory result. Confirmatory results were used to determine those participants who were HAHA positive.
A clinically significant asthma exacerbation was defined as a worsening of asthma symptoms, as judged clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose and/or treatment with systemic rescue corticosteroids for at least 3 days. The exacerbations rate per patient was derived using Poisson model adjusted by time at risk and the following covariates: country, exacerbation history, and dose schedule. A patient's person-days at risk was taken as the total amount of time (in days) he/she spent in the 24-week fixed-dose steroid treatment period.
See Adverse Events module for details.
To explore differences in pregnancy rate between asthmatic women receiving biological treatment vs. asthmatic women receiving normal asthma treatment and placebo. Pregnancy rate is defined as positive serum- Choriogonadotropin (in week 2) and ongoing pregnancy confirmed with ultra sound in week 7, after 3 consecutive IVF cycles. End of study measured as birth of life born infant or unsuccessful pregnancy
Proportion of patients with minimal urticarial dose (MUD) increased compared to baseline, under experimental conditions (assessed by phototesting). A small area of skin is exposed to increasing UVA doses with a solar simulator until an allergic reaction appears. The lower UVA dose triggering the urticaria is the MUD.
Patients receive provocation test by FricTest (standardized stroking of the skin). FricTest ratings are from 0 (no wheal development to the longest pin) to 4 (wheal development to all four pins). The development of wheals within 30 minutes after provocation is monitored.
Observed values and absolute change in FcεRI positive skin cells: dermis non-lesional and lesional. The primary variable for this study was the relative change from baseline in the high affinity IgE receptor (FcεRI) positive skin cells, based on skin biopsies collected from patients with CIU after 12 weeks of treatment.The values are average of cell numbers derived from counting 5 consecutive microscopic fields. Area counted is 5x 0.196 mm2
Observed values and absolute change in IgE positive skin cells: dermis non-lesional and lesional The primary variable for this study was the relative change from baseline in IgE positive skin cells, based on skin biopsies collected from patients with CIU after 12 weeks of treatment. The values are average of cell numbers derived from counting 5 consecutive microscopic fields. Area counted is 5x 0.196 mm2
The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total daily score (sum of the wheal and pruritus scores) ranges from 0 to 6. Because of variations in chronic urticaria disease intensity, assessment of disease activity was based on a weekly (7 days) UAS score called UAS7, that is, the sum of the daily UASs, ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change score (Week 24 score minus Baseline score) indicates improvement.
| Arm | Type | Description |
|---|---|---|
| Omalizumab | EXPERIMENTAL | Eligible patients randomized to this arm received omalizumab subcutaneously for 12 weeks |
| Placebo | PLACEBO_COMPARATOR | Eligible patients randomized to this arm received placebo subcutaneously for 12 weeks |
| Omalizumab 300mg | EXPERIMENTAL | patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8) |
| Omalizumab 150mg | EXPERIMENTAL | patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8) |
| Omalizumab 300 mg | EXPERIMENTAL | Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period. |
| Omalizumab 150 mg | EXPERIMENTAL | Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period. |
| 1 Omalizumab | EXPERIMENTAL | omalizumab once a month via subcutaneous injection. |
| 2 Placebo | PLACEBO_COMPARATOR | placebo of omalizumab once a month via subcutaneous injection |
| omalizumab arm | ACTIVE_COMPARATOR | The treatment is initiated with one injection with weight and serum-Immunoglobulin E balanced omalizumab one time per cyclus |
| placebo arm | PLACEBO_COMPARATOR | Participants will be administered placebo (NaCl), one time per cyclus |
| IGE025 | EXPERIMENTAL | Patients will receive omalizumab administered subcutaneously every 4 weeks at the study center. |
| Placebo to IGE025 | PLACEBO_COMPARATOR | Placebo administered subcutaneously every 4 weeks at the study center. |
| Omalizumab 75-375 mg | EXPERIMENTAL | Omalizumab was dosed at 75 to 375 mg according to baseline IgE and body weight as described in dosing tables in the study protocol. Dosing occurred subcutaneously every 2 or 4 weeks depending on dose. |
| Placebo to omalizumab | PLACEBO_COMPARATOR | Placebo to omalizumab was dosed at 75 to 375 mg according to baseline IgE and body weight as described in dosing tables in the study protocol. Dosing occurred subcutaneously every 2 or 4 weeks depending on dose. |
| Name | Type | Description |
|---|---|---|
| Omalizumab | DRUG | Omalizumab were administered by subcutaneous injection. Dose (75 to 600 mg) and dosing frequency (every 2 or 4 weeks) were determined by serum total IgE level (IU/mL) and body weight (kg) measured at the screening epoch according the dosing table. |
| Placebo | DRUG | Placebo were administered by subcutaneous injection. Dose (75 to 600 mg) and dosing frequency (every 2 or 4 weeks) were determined by serum total IgE level (IU/mL) and body weight (kg) measured at the screening epoch according the dosing table. |
| Fluticasone | DRUG | Patients entered the study using their current formulation of any inhaled steroid (proprietary drug and device) ≥ 200 μg/day equivalent of fluticasone administered with a dry-powder inhaler. |
| Omalizumab Injection | DRUG | The treatment is initiated with one injection with weight and serum-immunoglobulin E balanced omalizumab. After omalizumab treatment at ovulation it will again be collected material (blood samples, sputum, secretion of the vagina, secretion of the rectum, secretion of the uterus, microbiota). If no pregnancy has occurred after first IVF cycle, this will be repeated for 3 consecutive IVF cycles in total or until pregnancy has occurred. |
| NaCl | DRUG | The treatment is initiated with one injection with placebo. After placebo injection treatment at ovulation it will again be collected material (blood samples, sputum, secretion of the vagina, secretion of the rectum, secretion of the uterus, microbiota). If no pregnancy has occurred after first IVF cycle, this will be repeated for 3 consecutive IVF cycles in total or until pregnancy has occurred. |
| IGE025 | DRUG | Study medication will be supplied as a lyophilized, sterile powder in a single-use, 5-mL vial. |
| Omalizumab 75-375 mg | DRUG | Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 ml vial designed to deliver 150 mg of omalizumab upon reconstitution with 1.4 ml sterile water for injection. |
| Placebo to omalizumab | DRUG | Placebo to omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 ml vial designed to deliver 150 mg placebo to omalizumab upon reconstitution with 1.4 ml sterile water for injection. |
| Loratadine | DRUG | All participants received antihistamines on demand (loratadine and clemastine), as the trial was designed to investigate the effect of omalizumab as an add-on to antihistamines in people with chronic urticaria (CU). Administration of antihistamines is the current gold standard treatment of CU. A significant proportion of people with CU is not well controlled by this standard or by using high doses of antihistamines. |
| Clemastine | DRUG | All participants received antihistamines on demand (loratadine and clemastine), as the trial was designed to investigate the effect of omalizumab as an add-on to antihistamines in people with chronic urticaria (CU). Administration of antihistamines is the current gold standard treatment of CU. A significant proportion of people with CU is not well controlled by this standard or by using high doses of antihistamines. |
Inclusion criteria: * A clinical history of Japanese cedar pollinosis defined by the following * Took nasal corticosteroid plus one or more medications out of antihistamine (second generation), leukotriene receptor antagonist, or prostaglandin D2 thromboxane A2 receptor antagonist in Japanese ce...
IGE025 is an investigational small molecule being developed for chronic idiopathic urticaria, a condition characterized by recurrent hives without an identifiable cause. It is currently in Phase 2 clinical development and has not been approved by regulatory authorities.
IGE025 is being developed by Novartis AG, a multinational pharmaceutical company listed on the New York Stock Exchange under the ticker symbol NVS. The drug is currently in Phase 2 clinical trials for chronic idiopathic urticaria.
IGE025 is in Phase 2 clinical development. It is an investigational drug and has not yet received regulatory approval. A Phase 2 clinical trial for the drug has been completed, and it remains under evaluation for chronic idiopathic urticaria.
IGE025 has been studied in one completed Phase 2 clinical trial, identified as NCT01599637. This trial enrolled 40 participants with chronic idiopathic urticaria who had not responded to antihistamine treatment. The study was randomized, double-blind, and placebo-controlled, and was conducted in Germany.
IGE025 is not the same as omalizumab. Omalizumab is a biologic antibody, while IGE025 is a small molecule. The completed clinical trial NCT01599637 was a mode of action study of omalizumab in patients with chronic idiopathic urticaria, and IGE025 is a separate investigational drug.