NCT04092582

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller

Completed Phase 2 Results posted Last updated 14 August 2023

What this trial tests

Phase 2 trial testing MTPS9579A in Asthma in 135 participants. Completed in 19 May 2022.

Timeline

31 October 2019

Primary endpoint
19 May 2022

19 May 2022

Quick facts

Lead sponsor	Genentech, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	135
Start date	31 October 2019
Primary completion	19 May 2022
Estimated completion	19 May 2022
Sites	27 locations across Peru, Germany, Poland, Argentina, United States

Drugs / interventions tested

• MTPS9579A — full drug profile →
• Placebo

Conditions studied

• Asthma — all drugs for Asthma →

Sponsor

Genentech, Inc. — full company profile →

Who can join

Adults 18 to 75, any sex, with Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to First Composite Asthma Exacerbations (CompEX) Event Primary · Randomization [Week 2] to end of treatment (EOT) [Week 50]

CompEX is defined as time from randomization to first asthma exacerbation or diary worsening during the treatment period. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 da

Group	Value	95% CI
MTPS9579A, 1800 mg	NA	31.3 – NA
Placebo	45.4	19.0 – NA

Rate of Asthma Exacerbations Secondary · Randomization [Week 2] to Week 50

The number of asthma exacerbations per year was reported for this outcome measure. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Poisson regression was used for the

Group	Value	95% CI
MTPS9579A, 1800 mg	0.4689
Placebo	0.4267

Time to First Asthma Exacerbation Secondary · Randomization [Week 2] to Week 50

The time from randomization to first asthma exacerbation was measured. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Cox regression was used for the analysis.

Group	Value	95% CI
MTPS9579A, 1800 mg	NA	NA – NA
Placebo	NA	NA – NA

Absolute Change From Randomization in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 50 Secondary · Randomization [Week 2] to Week 50

FEV1 is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FEV1 as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FEV1 as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/microliter (uL)), number of asthma

Group	Value	95% CI
MTPS9579A, 1800 mg	0.11	± 0.034
Placebo	0.03	± 0.034

Relative Percent Change From Randomization in Pre-Bronchodilator FEV1 at Week 50 Secondary · Randomization [Week 2] to Week 50

FEV1 was the volume of air exhaled in the first second of a forced exhalation as measured by spirometer. Measurements were performed before use of bronchodilator. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the relative change pre-bronchodilator FEV1 as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FEV1 as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \

Group	Value	95% CI
MTPS9579A, 1800 mg	6.44	± 1.894
Placebo	3.15	± 1.921

Absolute Change From Randomization in Fractional Exhaled Nitric Oxide (FeNO) at Week 50 Secondary · Randomization [Week 2] to Week 50

FeNO is a volatile marker of airway inflammation that decreases with inhaled corticosteroid treatment. The measurements recorded were according to standardized procedures by the American Thoracic Society. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FeNO as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FeNO as well as its interaction with study visit, in addition to the stratification factors: b

Group	Value	95% CI
MTPS9579A, 1800 mg	-1.67	± 2.722
Placebo	-1.52	± 2.791

Relative Percent Change From Randomization in FeNO at Week 50 Secondary · Randomization [Week 2] to Week 50

FeNO is a volatile marker of airway inflammation that decreases with inhaled corticosteroid treatment. The measurements recorded were according to standardized procedures by the American Thoracic Society. Relative change (%) in FeNO = (absolute change in FeNO / baseline FeNO) x 100. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FeNO as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FeNO as well as

Group	Value	95% CI
MTPS9579A, 1800 mg	26.02	± 10.223
Placebo	26.29	± 10.482

Percentage of Participants With Adverse Events Secondary · Up to approximately Week 58

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.

Group	Value	95% CI
MTPS9579A, 1800 mg	79.7
Placebo	86.2

Area Under Concentration-Time Curve for the First Dosing Interval (AUClast) of MTPS9579A Secondary · Randomization [Week 2] to Week 6

Group	Value	95% CI
MTPS9579A, 1800 mg	5263.14	± 83.6

Maximum Serum Concentration (Cmax) for the First Dosing Interval of MTPS9579A Secondary · 2-hour post-dose on Week 2

Group	Value	95% CI
MTPS9579A, 1800 mg	419	± 51.4

Steady State Cmax of MTPS9579A Secondary · 2-hour post-dose on Week 14

Group	Value	95% CI
MTPS9579A, 1800 mg	735	± 31.0

Maximum Time to Serum Concentration (Tmax) of MTPS9579A Secondary · Pre-dose and 2-hour post-dose on Week 2

Group	Value	95% CI
MTPS9579A, 1800 mg	0.12	± 3.41

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately Week 58. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MTPS9579A, 1800 mg

Serious: 5/69 (7%)

Deaths: 1/69

Placebo

Serious: 4/65 (6%)

Deaths: 1/66

Serious adverse events (7 terms)

Reaction	System	MTPS9579A, 1800 mg	Placebo
COVID-19 pneumonia	Infections and infestations	—	—
Accidental death	General disorders	—	—
COVID-19	Infections and infestations	—	—
Clavicle fracture	Injury, poisoning and procedural complications	—	—
Tendon injury	Injury, poisoning and procedural complications	—	—
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	—	—
Dermatitis	Skin and subcutaneous tissue disorders	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	MTPS9579A, 1800 mg	Placebo
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
COVID-19	Infections and infestations	—	—
Nasopharyngitis	Infections and infestations	—	—
Headache	Nervous system disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: COVID-19 pneumonia, Accidental death, COVID-19, Clavicle fracture, Tendon injury, Abortion spontaneous, Dermatitis.

Data from ClinicalTrials.gov NCT04092582 adverse events section.

Sponsor's own description

This is a Phase IIa, randomized, placebo-controlled, double-blind, multicenter, two-arm study to evaluate the efficacy, safety, and pharmacokinetics of MTPS9579A as an add-on therapy in patients with uncontrolled moderate to severe asthma who are receiving daily ICS therapy and at least one of the following additional controller medications: long-acting beta-agonist (LABA), leukotriene modulator (leukotriene modifier \[LTM\] or leukotriene receptor antagonist \[LTRA\]), long-acting muscarinic antagonist (LAMA), or long-acting theophylline preparation.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical relevance of inherited genetic differences in human tryptases: Hereditary alpha-tryptasemia and beyond.
   Glover SC, Carter MC, Korošec P, Bonadonna P, et al · · 2021 · cited 45× · PMID 34400315 · DOI 10.1016/j.anai.2021.08.009
2. Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis.
   Das N, de Almeida LGN, Derakhshani A, Young D, et al · · 2023 · cited 42× · PMID 37024468 · DOI 10.1038/s41467-023-37598-3
3. New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis.
   Striz I, Golebski K, Strizova Z, Loukides S, et al · · 2023 · cited 37× · PMID 37199256 · DOI 10.1042/cs20190281
4. Human Lung Mast Cells: Therapeutic Implications in Asthma.
   Poto R, Criscuolo G, Marone G, Brightling CE, et al · · 2022 · cited 26× · PMID 36430941 · DOI 10.3390/ijms232214466
5. Dose-dependent inactivation of airway tryptase with a novel dissociating anti-tryptase antibody (MTPS9579A) in healthy participants: A randomized trial.
   Rymut SM, Sukumaran S, Sperinde G, Bremer M, et al · · 2022 · cited 15× · PMID 34581002 · DOI 10.1111/cts.13163
6. Advances in Biologic Therapies for Allergic Diseases: Current Trends, Emerging Agents, and Future Perspectives.
   Alska E, Łaszczych D, Napiórkowska-Baran K, Szymczak B, et al · · 2025 · cited 13× · PMID 40004611 · DOI 10.3390/jcm14041079
7. Non allergic gastrointestinal manifestations of hereditary alpha-tryptasemia.
   Vainer D, Peterson K. · · 2025 · PMID 40556656 · DOI 10.3389/falgy.2025.1598309