A Randomized, Double Blind, Active-Controlled Study on Efficacy and Safety of TEV-56248 in Patients with Asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Teva Branded Pharmaceutical Products R&D LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

4 Jun 2024 → ongoing

Decision date (initial)

2024-04-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Teva Branded Pharmaceutical Products R&D LLC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Prophylaxis, Therapy, Efficacy

Primary objective of the study is to assess the efficacy of high dose (HD) fluticasone propionate (Fp)/albuterol sulfate (ABS) integrated electronic module multidose dry powder inhaler (eMDPI) compared to ABS eMDPI in decreasing severe CAEs when used as a rescue medication.

Secondary objectives 3

1. - Evaluate the efficacy of Fp/ABS eMDPI 2 inhalations taken as needed (prn) compared to that with ABS eMDPI 2 inhalations prn and the effect on systemic corticosteroid (SCS) exposure.
2. - Evaluate the safety and tolerability of Fp/ABS eMDPI 2 inhalations prn over 24 weeks
3. - Assess the efficacy of low dose (LD) Fp/ABS eMDPI compared to ABS eMDPI in decreasing severe CAEs when used as a rescue medication.

Conditions and MedDRA coding

Asthma

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. a. The patient is capable of giving signed informed consent (age ≥18 years). Patients ages 4 to <18 years (or as applicable and required by local regulation) are able to provide assent and written consent must be provided by a parent/legally acceptable representative before any study procedures are performed.
2. b. The patient is a male or female 4 years of age or older at the time of informed consent/assent or age as allowed by local regulation.
3. c. The patient has a documented diagnosis of asthma for at least 1 year according to the 2022 GINA guidelines.
4. d. The patient has an ACQ-5 score of ≥1.5 at the screening visit. (Patients aged 4-5 years are not required to meet this criteria).
5. e. The patient has a documented history of at least 1 severe CAE ending within the past 12 month.
6. f. The patient is using any prescribed inhaled asthma controller medication (at a stable dose for 1 month prior to the screening visit).
7. g. Patients aged 18 years and older must have a screening (V1) prebronchodilator FEV1 of ≥40 to <90% predicted normal value. Patients aged 4 to 17 years at the time of screening must have an FEV1 of ≥60% predicted normal value (Quanjer et al 2012) after withholding specified medications including SABA (rescue medication) for spirometry testing. Patients are not required to meet these criteria at V3. Patients failing to meet these criteria are allowed a single additional retest during the screening period in advance of the second visit.

Exclusion criteria 11

1. a. The patient has any asthma worsening requiring a change in asthma treatment other than SABA and/or short-acting anticholinergic agent within 30 days prior to screening or during the run-in period.
2. b. The patient has life-threatening asthma defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s) within 5 years before screening.
3. c. The patient has a suspected bacterial or viral infection (other than Coronavirus Disease [COVID-19]) of the upper or lower respiratory tract, sinus, or middle ear that has not resolved at least 2 weeks before the screening period.
4. d. Patients with a confirmed infection with COVID-19 within 6 weeks prior to the screening visit, or with residual COVID-19 symptoms ("long COVID-19”).
5. e. Patients with clinical symptoms that may indicate COVID-19 infection.
6. f. The patient is currently being treated with a prohibited medication (Appendix G) including SCS or biological medications used to treat asthma or malignancy.
7. g. The patient has cancer not in complete remission for at least 5 years.
8. h. The patient has had a CAE requiring systemic corticosteroids within 30 days before screening, or any hospitalization for asthma within 2 months before screening.
9. i. The patient has used SCS (any dose and any indication) within 30 days prior to screening.
10. j. The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis,pulmonary fibrosis), or participants with a diagnosis of asthma COPD overlap syndrome (ACOS).
11. k. The patient is a current smoker and/or has a history of ≥10 pack – years history of smoking. A current smoker is defined as any participant who has used any form of tobacco product (including oral) within the past 6 months or any orally inhaled products including but not limited to cigarettes, beedis vaping, e-cigarettes, hookah/waterpipes or marijuana. Note: participants with a positive urinary cotinine test will be excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first severe CAE with HD Fp/ABS eMDPI.

Secondary endpoints 5

1. The key efficacy endpoints: - annualized severe CAE rate '- total annualized SCS exposure over the treatment period
2. - Asthma Control Questionnaire-5 (ACQ-5) response at week 24, defined as achieving a decrease in score from baseline value of at least 0.5
3. - Asthma Quality of Life Questionnaire + 12 (AQLQ+12) response at week 24, defined as achieving an increase from baseline of at least 0.5
4. Safety/Tolerability endpoints: '- occurrence of adverse events during the study '- occurrence of serious adverse events during the study '- study withdrawal due to treatment-emergent adverse events
5. - Time to first severe CAE with LD Fp/ABS eMDPI

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Teva Branded Pharmaceutical Products R&D LLC

Sponsor organisation

Teva Branded Pharmaceutical Products R&D LLC

Address

145 Brandywine Parkway

City

West Chester

Postcode

19380-4245

Country

United States

Scientific contact point

Organisation

Teva Branded Pharmaceutical Products R&D LLC

Contact name

Medical Information

Public contact point

Organisation

Teva Branded Pharmaceutical Products R&D LLC

Contact name

Medical Information

Third parties 8

Locations

12 EU/EEA countries · 102 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 612 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

31 submissions — initial application plus substantial / non-substantial modifications