PIVOTAL TRIAL: STUDY DESIGN1

Study 200622

Phase 3, randomized, placebo-controlled, double-blind study

Study 200622 design: phase 3, randomized, placebo-controlled, double-blind study

Study 200622 design: phase 3, randomized, placebo-controlled, double-blind study

Description

32-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing NUCALA 300 mg SC to placebo, each added to stable HES therapy in 108 patients aged ≥12 years with HES.

Key inclusion criteria

  • Diagnosed with HES* ≥6 months prior to baseline
  • Blood eosinophil counts ≥1000 cells/µL during screening
  • ≥2 HES flares† in the past 12 months
    • At least one of these HES flares must not have been related to a decrease in therapy during the 4 weeks prior to the flare

Key exclusion criteria1,2

  • Patients with non-hematologic secondary HES (eg, drug hypersensitivity, parasitic helminth infection, HIV infection, non-hematologic malignancy)
  • Patients with FIP1L1-PDGFRA kinase-positive HES

Stable HES therapy

  • Existing HES therapy, which included but was not limited to chronic or episodic corticosteroids, immunosuppressants, or cytotoxic therapy

Primary endpoint results:

Proportion of patients who experienced HES flare(s)‡ during the 32-week study or withdrew. NUCALA 28% vs placebo 56%, P=0.002

Select secondary endpoints:

  • Time to first flare
  • Change from baseline in Brief Fatigue Inventory Item 3 at Week 32
  • *HES diagnosis was based on signs or symptoms of organ system involvement and/or dysfunction that could be directly related to blood eosinophilia of >1500 eosinophils/μL on ≥2 occasions, and/or tissue eosinophilia.
  • †Historical flares for study entry criteria were defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an escalation in treatment.
  • ‡HES flare defined as a worsening of clinical signs/symptoms or increased eosinophils (on ≥2 occasions), resulting in an escalation/addition of oral corticosteroids (OCS) or cytotoxic or immunosuppressive therapy.
  • SC=subcutaneous.

Hear from a peer about NUCALA

EGPA vs HES | 9:06

An expert in allergy and immunology describes how to differentiate two diseases related to peripheral blood eosinophilia: eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES).

Navigate a NUCALA prescription

Start with MyNUCALA keyboard_arrow_right

DISCOVER OUR SAFETY PROFILE IN HES

View Safety

AT-HOME OR IN-OFFICE DOSING & ADMINISTRATION

Explore Dosing
HES patient looking at children

ACCESS YOUR TOGETHER WITH NUCALA ENROLLMENT FORM

Visit Access and Support

INDICATIONS & IMPORTANT SAFETY INFO

INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS

NUCALA is indicated for the: 

  • treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for greater than or equal to 6 months without an identifiable non-hematologic secondary cause.
  • add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus.
  • add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients aged 18 years and older with inadequate response to nasal corticosteroids.
  • add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm.
  • treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Known hypersensitivity to mepolizumab or excipients.

 

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred with NUCALA. These reactions generally occur within hours of administration but can have a delayed onset (ie, days). Discontinue if a hypersensitivity reaction occurs.

 

Acute Symptoms of Asthma or COPD or Acute Deteriorating Disease

NUCALA should not be used to treat acute symptoms or acute exacerbations of asthma or COPD, or acute bronchospasm.

 

Opportunistic Infections: Herpes Zoster

Herpes zoster infections have occurred in patients receiving NUCALA. Consider vaccination if medically appropriate.

 

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with NUCALA. Decreases in corticosteroid doses, if appropriate, should be gradual and under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

 

Parasitic (Helminth) Infection

Treat patients with pre-existing helminth infections before initiating therapy with NUCALA. If patients become infected while receiving NUCALA and do not respond to anti-helminth treatment, discontinue NUCALA until infection resolves.

 

ADVERSE REACTIONS

Most common adverse reactions (≥5%):

  • Severe asthma trials: headache, injection site reaction, back pain, fatigue
  • CRSwNP trial: oropharyngeal pain, arthralgia
  • COPD trials: back pain, diarrhea, cough
  • EGPA and HES trials (300 mg of NUCALA): most common adverse reactions were similar to severe asthma

Systemic reactions, including hypersensitivity, occurred in clinical trials in patients receiving NUCALA. Manifestations included rash, pruritus, headache, myalgia, flushing, urticaria, erythema, fatigue, hypertension, warm sensation in trunk and neck, cold extremities, dyspnea, stridor, angioedema, and multifocal skin reaction. A majority of systemic reactions were experienced the day of dosing.

 

USE IN SPECIFIC POPULATIONS

The data on pregnancy exposures are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are transported across the placenta in a linear fashion as the pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters.

 

Please see full Prescribing Information and Patient Information for NUCALA.

PMUS-MPLWCNT240088 May 2025

To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. Roufosse F, Kahn JE, Rothenberg ME, et al. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;146(6):1397-1405.

  2. Data on file, GSK.