ADL-018 vs Omalizumab for Chronic Urticaria

Recruiting at 3 trial locations

Overseen By Dr Prayag N shah, MD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Kashiv BioSciences, LLC

Must be taking: H1 antihistamines

Must not be taking: Corticosteroids, Hydroxychloroquine, Methotrexate, others

Disqualifiers: Malignancy, Cardiovascular, Neurological, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

600 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two medications, ADL-018 and XOLAIR, to treat patients with a chronic skin condition who still have symptoms despite taking antihistamines. The medications are given as injections periodically and work by calming the immune system to reduce skin symptoms.

Do I have to stop taking my current medications to join the trial?

Yes, you may need to stop certain medications. You must stop using systemic or topical corticosteroids, hydroxychloroquine, methotrexate, cyclosporine, cyclophosphamide, investigational agents, IVIG, plasmapheresis, regular doxepin, H2 antihistamines, and LTRAs within specific timeframes before screening. However, you must continue using an H1 antihistamine for at least 3 consecutive days before screening.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. You must not use systemic or topical corticosteroids, hydroxychloroquine, methotrexate, cyclosporine, cyclophosphamide, or certain investigational agents within 10 days before screening. Additionally, you must stop using H2 antihistamines 7 days before, and LTRA medications 10 to 14 days before screening.

What data supports the idea that ADL-018 vs Omalizumab for Chronic Urticaria is an effective drug?

The available research shows that Omalizumab, a drug similar to ADL-018, is effective in treating chronic urticaria. In clinical trials, Omalizumab significantly reduced itching and the number and size of hives in patients who did not respond to standard antihistamines. It also improved patients' quality of life and reduced the number of days with swelling. Most side effects were mild or moderate, making it a well-tolerated option. This suggests that ADL-018, being similar, could also be effective for this condition. ^{1 2 3 4 5}

What data supports the effectiveness of the drug ADL-018 for treating chronic urticaria?

Omalizumab, a drug similar to ADL-018, has been shown to effectively reduce itching and hives in patients with chronic spontaneous urticaria who did not respond to antihistamines, improving their quality of life. It is generally well-tolerated, with mild to moderate side effects similar to those of a placebo. ^{1 2 3 4 5}

What safety data is available for ADL-018 and Omalizumab in treating chronic urticaria?

Omalizumab (Xolair) has been extensively studied for safety. In clinical trials for chronic spontaneous urticaria, it was generally well tolerated with adverse events similar to placebo, mainly mild or moderate, such as headache and upper respiratory infections. Anaphylaxis was rare, occurring in 0.1% of asthma patients in pre-marketing trials and at least 0.2% in post-marketing reports. A biosimilar, CMAB007, showed no drug-related adverse events in healthy subjects. Overall, omalizumab is considered safe and well-tolerated for treating chronic urticaria. ^{1 2 3 6 7}

Is the treatment ADL-018 or Omalizumab safe for humans?

Omalizumab (Xolair) has been generally well-tolerated in clinical trials for conditions like asthma and chronic urticaria, with most side effects being mild or moderate. Anaphylaxis (a severe allergic reaction) was rare, occurring in about 0.1% to 0.2% of patients. In studies, the safety profile of omalizumab was similar to placebo, with headache and upper respiratory infections being slightly more common. ^{1 2 3 6 7}

Is the drug ADL-018 (Omalizumab) a promising treatment for chronic urticaria?

Yes, ADL-018 (Omalizumab) is a promising treatment for chronic urticaria. It has been shown to significantly reduce itching, hives, and improve quality of life for patients who do not respond to standard antihistamine treatments. It is well-tolerated and is the only licensed treatment for chronic urticaria that doesn't respond to antihistamines. ^{1 2 3 4 8}

How does the drug ADL-018 differ from other treatments for chronic urticaria?

ADL-018 is being compared to Omalizumab, a drug that works by blocking IgE (a type of antibody involved in allergic reactions) to reduce symptoms of chronic urticaria. Omalizumab is unique because it is the only licensed treatment for chronic urticaria that doesn't respond to antihistamines, and it is administered as an injection every four weeks. ^{1 2 3 4 8}

Eligibility Criteria

Adults aged 18-75 with Chronic Idiopathic Urticaria (CIU) who haven't improved on antihistamines can join. Women must use birth control or be non-childbearing, and all participants should commit to the study schedule. Excluded are those recently in other drug trials, with known causes for their hives, certain medical conditions or treatments, cancer history, substance abuse issues, or infections like hepatitis or HIV.

Inclusion Criteria

I am between 18 and 75 years old.

I agree to use birth control during and for 6 months after the study.

Capable of providing written informed consent, adhering to all visit schedules, and meeting study requirements.

Exclusion Criteria

I do not have a history of severe allergies, significant diseases, substance abuse, or current pregnancy.

Participation in a clinical trial involving the administration of an investigational drug or marketed drug within 30 days prior to initial dosing (90 days for biologics).

You have signs of a parasitic infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 2 weeks

Treatment

Participants receive ADL-018 or XOLAIR every 4 weeks for 24 weeks, including a 12-week main treatment period and a 12-week transition period

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Treatment Details

Interventions

• ADL-018
• XOLAIR (Omalizumab)

Trial Overview The trial is testing ADL-018 against XOLAIR (Omalizumab), both given as injections to see which one works better for chronic hives when regular antihistamines don't help. Participants will receive either ADL-018 or XOLAIR while continuing their antihistamine treatment.

Participant Groups

Group I: Xolair-300 mg Main / ADL-018 300 mg Transition Period Experimental Treatment 2 Interventions

ADL-018 (Omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 12,16,20 in patients that were randomized to Xolair-300 mg in the main treatment period.

Group II: Xolair-150 mg Main / ADL-018150 mg Transition Period Experimental Treatment 2 Interventions

ADL-018 (Omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 12,16,20 in patients that were randomized to XOLAIR-150 mg in the main treatment period.

Group III: ADL-018 300 mg Main Treatment period Experimental Treatment 1 Intervention

ADL-018 (Omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 0, 4, 8

Group IV: ADL-018 300 mg Main / ADL-018 300 mg Transition Period Experimental Treatment 1 Intervention

ADL-018 (Omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 12,16,20 in patients that were randomized to ADL-018 300 mg in the Main Treatment period.

Group V: ADL-018 150 mg Main Treatment period Experimental Treatment 1 Intervention

ADL-018 (Omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 0, 4, 8

Group VI: ADL-018 150 mg Main / ADL-018 150 mg Transition Period Experimental Treatment 1 Intervention

ADL-018 (Omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 12,16,20 in patients that were randomized to ADL-018150 mg in the main treatment period.

Group VII: Xolair-150 mg Main Treatment Period Active Control 1 Intervention

XOLAIR (omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 0, 4, 8

Group VIII: Xolair-300 mg Main / Xolair-300 mg Transition Period Active Control 1 Intervention

XOLAIR (omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 12,16,20 in patients that were randomized to Xolair-300 mg in the main treatment period.

Group IX: Xolair-150 mg Main / Xolair-150 mg Transition Period Active Control 1 Intervention

XOLAIR (omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 12,16,20 in patients that were randomized to XOLAIR -150 mg in the main treatment period.

Group X: Xolair-300 mg Main Treatment Period Active Control 1 Intervention

XOLAIR (omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 0, 4, 8

ADL-018 is already approved in European Union, United States for the following indications:

Approved in European Union as XOLAIR for:

• Chronic idiopathic urticaria
• Severe persistent allergic asthma
• Chronic rhinosinusitis with nasal polyps

Approved in United States as XOLAIR for:

• Chronic idiopathic urticaria
• Severe persistent allergic asthma
• Chronic rhinosinusitis with nasal polyps
• IgE-mediated food allergy

Who Is Running the Clinical Trial?

Kashiv BioSciences, LLC

Lead Sponsor

Trials

4

Recruited

1,200+

COD Research Private Ltd

Collaborator

Trials

2

Recruited

630+

Findings from Research

Omalizumab, a monoclonal antibody used to treat IgE-mediated diseases, has a low incidence of anaphylaxis, reported in only 0.1% of asthma patients during clinical trials and estimated at 0.2% in post-marketing studies.

A post-marketing study found no correlation between anaphylaxis or skin test reactions and the presence of IgE antibodies to omalizumab, suggesting that the risk of anaphylaxis may not be related to the drug's immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of IgE Antibodies to Omalizumab (Xolair®) and Their Potential Correlation to Anaphylaxis. Baker, DL., Nakamura, GR., Lowman, HB., et al.[2018]

Omalizumab is an effective add-on therapy for patients with chronic spontaneous urticaria, significantly reducing itching and hives severity, and improving quality of life compared to placebo in well-controlled trials lasting 12 to 24 weeks.

The treatment is generally well tolerated, with adverse events similar in frequency and severity to those experienced by placebo recipients, primarily involving mild to moderate headaches and upper respiratory infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab: a review of its use in patients with chronic spontaneous urticaria. McCormack, PL.[2021]

In a study of 11 patients with chronic spontaneous urticaria, 9 achieved complete resolution of symptoms after treatment with omalizumab, with an average time to remission of 9.3 weeks.

Omalizumab was found to be safe, as no side effects were reported during the treatment, indicating its potential as an effective option for patients unresponsive to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab for urticaria treatment in clinical practice: a case series. Lesiak, A., Bednarski, IA., Maćkowska, A., et al.[2022]

A study involving 6038 patients showed that nearly all individuals starting treatment with omalizumab had previously used multiple asthma medications, indicating that they were likely experiencing severe asthma symptoms despite existing treatments.

A significant number of new omalizumab users had recent asthma-related emergency room visits (up to 36% in Medicaid) or hospitalizations, highlighting the need for effective management in patients with moderate to severe persistent allergic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant asthma medication use in patients receiving omalizumab: results from three large insurance claims databases. Lafeuille, MH., Duh, MS., Zhang, J., et al.[2015]

In a study of 7 patients with various types of physical urticaria, treatment with omalizumab (Xolair®) led to complete symptom control within days for 5 patients, demonstrating its rapid efficacy.

Omalizumab was found to be a safe and effective option for patients who had previously struggled with physical urticaria for years and had not responded to standard antihistamines or other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-immunoglobulin E treatment of patients with recalcitrant physical urticaria. Metz, M., Altrichter, S., Ardelean, E., et al.[2015]

CMAB007, a biosimilar of omalizumab, was well-tolerated in a study involving 36 healthy Chinese men, with no drug-related adverse events reported, indicating a favorable safety profile.

The treatment effectively reduced free IgE levels by 91.9-98.8% in a dose-dependent manner, demonstrating its pharmacodynamic efficacy and supporting its potential for further clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability, pharmacokinetics and pharmacodynamics of CMAB007, a humanized anti-immunoglobulin E monoclonal antibody, in healthy Chinese subjects. Zhou, B., Lin, B., Li, J., et al.[2021]

Omalizumab (Xolair) is an effective treatment for moderate-to-severe persistent asthma in patients aged 12 and older who have a positive reaction to allergens and whose symptoms are not well controlled by inhaled corticosteroids, based on data from over 5,243 patients in 12 clinical trials.

The safety profile of omalizumab is comparable to that of placebo or standard therapy, indicating it is a well-tolerated option for managing IgE-mediated asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody. Deniz, YM., Gupta, N.[2022]

Chronic urticaria affects many patients, with about 50% not responding to standard treatment with second-generation H1-antihistamines, highlighting the need for effective alternatives.

Omalizumab (Xolair™) is the only licensed treatment for patients who do not respond to antihistamines, showing a favorable safety profile and good tolerability in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab for the treatment of chronic urticaria. Zuberbier, T., Maurer, M.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of IgE Antibodies to Omalizumab (Xolair®) and Their Potential Correlation to Anaphylaxis. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Omalizumab: a review of its use in patients with chronic spontaneous urticaria. [2021]

3. Poland pubmed.ncbi.nlm.nih.gov

Omalizumab for urticaria treatment in clinical practice: a case series. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Concomitant asthma medication use in patients receiving omalizumab: results from three large insurance claims databases. [2015]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Anti-immunoglobulin E treatment of patients with recalcitrant physical urticaria. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Tolerability, pharmacokinetics and pharmacodynamics of CMAB007, a humanized anti-immunoglobulin E monoclonal antibody, in healthy Chinese subjects. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Safety and tolerability of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Omalizumab for the treatment of chronic urticaria. [2015]