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

A Phase IIa, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: MTPS9579A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Fundacion CIDEA
  • Buenos Aires, Argentina, C1426ABO
    • Centro Médico Dra. Cristina de Salvo
  • Caba, Argentina, C1414AIF
    • CARE - Centro de Alergia y Enfermedades Respiratorias
  • Quilmes, Argentina, B1878FNR
    • Centro Respiratorio Quilmes
• Germany
  • Berlin, Germany, 10717
    • Research Center for Medical Studies RCMS
  • Frankfurt am Main, Germany, 60596
    • IKF Pneumologie
  • Hannover, Germany, 30173
    • Pneumologicum
  • Leipzig, Germany, 04275
    • BAG Prof Dr G Hoheisel Dr A Bonitz
  • Magdeburg, Germany, 39120
    • SMO.MD GmbH, Zentrum für klinische Studien
• Peru
  • Lima, Peru, 32
    • Clinica Providencia (Inverconsult Sociedad Anonima)
  • Lima, Peru, Lima 27
    • Clinica Ricardo Palma; THORAX
• Poland
  • Bialystok, Poland, 15-003
    • Centrum Medycyny Oddechowej Robert M. Mróz
  • Krakow, Poland, 30-033
    • Centrum Medyczne ALL-MED
  • Krakow, Poland, 30-727
    • Malopolskie Centrum Alergologii
  • Lodz, Poland, 90-153
    • SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
  • Ostrowiec Swietokrzysk, Poland, 27-400
    • Ostrowieckie Centrum Medyczne Spolka Cywilna Anna Olec-Cudzik; Krzysztof Cudzik
  • Poznan, Poland, 60-214
    • Centrum Alergologii Teresa Hofman
  • Sosnowiec, Poland, 41-200
    • PULMAG Grzegorz Gasior Marzena Kociolek Spolka Cywilna
  • Wroclaw, Poland, 50-445
    • ALL-MED Specjalistyczna Opieka Medyczna
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Kern Research
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Medical Group of the Bay Area
  • Florida
    • Miami, Florida, United States, 33173
      • Florida Ctr-Allergy & Asthma
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute, LLC
  • Ohio
    • Toledo, Ohio, United States, 43617
      • Toledo Inst of Clin Research
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • OK Clinical Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented physician-diagnosed asthma for at least 12 months prior to screening
• Treatment with asthma controller therapy (daily ICS [fluticasone propionate or equivalent] and at least one additional controller therapy [LABA, LAMA, LTM/LTRA]) for >= 3 months prior to screening, with no changes within 4 weeks prior to screening or during the screening period and no anticipated changes in controller dosing regimens throughout the study
• Documented history of >= 2 asthma exacerbation within the 12 months prior to screening while on daily ICS maintenance therapy
• For women of childbearing potential: agreement to remain abstinent or use contraception For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

• History or evidence of vocal cord dysfunction, reactive airways dysfunction syndrome, hyperventilation associated with panic attacks, or other mimics of asthma
• History or evidence of significant respiratory disease other than asthma, including occupational asthma, aspirin-sensitive asthma, asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome, bronchiolitis, interstitial lung disease, or COPD
• Current smoker, electronic cigarette (e-cigarette) user, former smoker with smoking history of > 10 pack-years, former e-cigarette user with an e-cigarette history of at least daily use for >=10 years, or unwilling to abstain from smoking and/or e-cigarette use from the time of consent through the completion of the study
• History or evidence of any clinically significant medical condition/disease or abnormalities in laboratory tests that, in the investigator's judgment, precludes the patient's safe participation and completion of the study, or interferes with the conduct and interpretation of the study
• Active malignancy or history of malignancy within 5 years of screening, except for appropriately treated non-melanoma skin carcinoma, cervical carcinoma in situ, breast ductal carcinoma in situ, or Stage I uterine cancer
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of MTPS9579A
• Positive for TB at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo matching MTPS9579A will be administered at the randomization visit (Week 2), Week 6, and every 4 weeks thereafter through Week 46.
Experimental: MTPS9579A	Drug: MTPS9579A; MTPS9579A IV infusion will be administered at the randomization visit (Week 2), Week 6, and every 4 weeks through Week 46.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Composite Asthma Exacerbations (CompEX) Event	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 days. Diary worsening is based on the occurrence of prespecified changes in the following six parameters: morning peak expiratory flow rate (PEFR), evening PEFR, morning symptom score, evening symptom score, morning short-acting rescue therapy use, and evening short-acting rescue therapy use. Hazard ratio was used for the analysis.	Randomization [Week 2] to end of treatment (EOT) [Week 50]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Asthma Exacerbations	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 analysis.	Randomization [Week 2] to Week 50
Time to First Asthma Exacerbation	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.	Randomization [Week 2] to Week 50
Absolute Change From Randomization in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at 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 exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or >=2 events), and geographic region.	Randomization [Week 2] to Week 50
Relative Percent Change From Randomization in Pre-Bronchodilator FEV1 at 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, >=150 to <=300, >300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or >=2 events), and geographic region. Relative change (%) in FEV1 = (absolute change in FEV1 / baseline FEV1) x 100.	Randomization [Week 2] to Week 50
Absolute Change From Randomization in Fractional Exhaled Nitric Oxide (FeNO) at 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: blood eosinophil level at visit 1 (<150, >=150 to <=300, >300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or >=2 events), and geographic region.	Randomization [Week 2] to Week 50
Relative Percent Change From Randomization in FeNO at 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 its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (<150, >=150 to <=300, >300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or >=2 events), and geographic region.	Randomization [Week 2] to Week 50
Percentage of Participants With Adverse Events	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.	Up to approximately Week 58
Area Under Concentration-Time Curve for the First Dosing Interval (AUClast) of MTPS9579A		Randomization [Week 2] to Week 6
Maximum Serum Concentration (Cmax) for the First Dosing Interval of MTPS9579A		2-hour post-dose on Week 2
Steady State Cmax of MTPS9579A		2-hour post-dose on Week 14
Maximum Time to Serum Concentration (Tmax) of MTPS9579A		Pre-dose and 2-hour post-dose on Week 2
Trough Serum Concentration (Ctrough) Accumulation Ratio of MTPS9579A	The accumulation ratio is calculated by taking the individual ratio of the Ctrough at Week 14 to the Ctrough at Week 6.	Predose on Weeks 6 and 14
Steady State Ctrough of MTPS9579A		Pre-dose on Week 14
Percentage of Participants With Anti-Drug Antibodies (ADA) to MTPS9579A	Treatment Emergent ADA is (a) negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, OR (b) positive ADA result at baseline and one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result.	Pre-dose Week 54

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2019
• Primary Completion (Actual): May 19, 2022
• Study Completion (Actual): May 19, 2022

Study Registration Dates

• First Submitted: September 13, 2019
• First Submitted That Met QC Criteria: September 13, 2019
• First Posted (Actual): September 17, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: GB41149; 2019-000795-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No