Dose ranging study of amlitelimab in adult participants with moderate-to-severe asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

17 Jan 2023 → 21 Mar 2025

Decision date (initial)

2024-05-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-510641-33-00

EudraCT number

2022-000065-41

WHO UTN

U1111-1272-2612

ClinicalTrials.gov

NCT05421598

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacodynamic, Dose response, Pharmacokinetic

To evaluate the efficacy of different doses of amlitelimab compared to placebo in participants with moderate-to-severe, uncontrolled asthma

Secondary objectives 14

1. To evaluate the effects of amlitelimab compared to placebo on lung function as measured by forced expiratory volume in 1 second (FEV1)
2. To evaluate the effects of amlitelimab on Asthma Control Questionnaire 5 (ACQ-5)
3. To evaluate the effects of amlitelimab on time to first severe exacerbation event
4. To evaluate the effects of amlitelimab on other spirometry assessments
5. To evaluate the effects of amlitelimab on fraction of exhaled nitric oxide (FeNO)
6. To evaluate the effects of amlitelimab compared to placebo on reducing the incidence of “loss of asthma control” (LOAC) events
7. To evaluate the effects of amlitelimab on time to first LOAC event
8. To evaluate the effects of amlitelimab on asthma symptoms
9. To evaluate the effects of amlitelimab on reducing the incidence of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit
10. Assess the effect of amlitelimab on bronchodilator (BD) therapy
11. To evaluate the pharmacokinetic (PK) of amlitelimab and anti-drug antibodies to amlitelimab in participants with asthma
12. To evaluate the safety of amlitelimab in participants with asthma
13. To evaluate the effects of amlitelimab on participant reported outcomes (PROs)
14. To evaluate the effects of amlitelimab on Asthma Control Questionnaire 6 and 7

Conditions and MedDRA coding

Asthma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. The participant must be between the ages of 18 and 75 inclusive at the time of signing the informed consent.
2. Moderate to severe asthma diagnosed by a physician for ≥ 12 months according to stages 4 and 5 of the Global Initiative for Asthma (GINA ).
3. Participants on existing therapy with medium to high doses of ICS (≥500 μg fluticasone propionate daily or comparable ICS dose in combination with at least one additional controller (e.g., long-acting beta agonist [LABA], leukotriene receptor antagonist [LTRA], long-acting muscarinic Antagonist [LAMA], methylxanthines) for at least 3 months.
4. ≥ 1 severe asthma exacerbation in the past year, with at least one exacerbation during treatment with medium to high doses of ICS (≥ 500 μg fluticasone propionate daily or one dose of ICS comparable).
5. Participants with pre-BD forced expiratory volume in 1 second (FEV1) > 40% and < 80% of predicted normal at the screening visit.
6. 5-item ACQ-5 score >1.5 at randomization.
7. Participants with at least 12% reversibility and 200 mL post-BD FEV after administration of albuterol/salbutamol or levalbuterol/levosalbutamol at screening or documented history of a reversibility test.
8. Weight ≥40 kg and ≤150 kg at the randomization visit.

Exclusion criteria 14

1. Chronic lung disease other than asthma.
2. Current or former smoker including active vaping of any products and/or marijuana with cessation within 6 months of screening or history of >10 pack-years.
3. Participants who experience a deterioration of asthma that results in emergency treatment or hospitalization, or treatment with systemic steroids at any time from 1 month prior to screening.
4. Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection during the screening period including known history of COVID-19 infection within 4 weeks prior to Screening; mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 3 months prior to Screening; COVID-19 infection who have not yet sufficiently recovered to participate in the procedures of a clinical trial.
5. Active infection or history of clinically significant infection
6. Known history of, or suspected, significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
7. Active or latent tuberculosis (TB)
8. A history of malignancy of any type (excluding basal and squamous cell skin cancer and in situ cervical carcinoma that has been excised and cured >3 years prior to baseline).
9. History of solid organ transplant.
10. Hepatitis B, C or HIV.
11. Pregnant or breastfeeding.
12. History (within last 2 years prior to Baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator.
13. Any prior use of anti-OX40 or anti-OX40L mAb, including amlitelimab
14. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of severe exacerbation events over 48 weeks

Secondary endpoints 24

1. Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48
2. Change from baseline in Asthma Control Questionnaire 5 (ACQ-5) score at Week 48
3. Change from baseline in Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at Week 48
4. Change from baseline in post-BD FEV1 at Week 48
5. The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD)
6. Change from baseline in ACQ-5 score at Weeks 2, 4, 8, 12, 24, 36, and 60
7. Time to first severe exacerbation event
8. Change from baseline in pre-BD and post-BD FEV1
9. Change from baseline in peak expiratory flow (PEF) and forced expiratory flow (FEF) 25-75%
10. Change from baseline in forced vital capacity (FVC)
11. Change from baseline in FeNO at Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60
12. Annualized rate of loss of asthma control (LOAC) events during 48 weeks of treatment
13. Time to first LOAC event
14. Change from baseline in the Asthma Daytime Symptom Diary (ADSD) 6-item daily morning score and in the Asthma Nighttime Symptom Diary (ANSD) 6-item daily evening scores at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
15. Annualized rate of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit during 48 weeks of treatment
16. Change from baseline in the numbers of inhalations/day of SABA or low-dose ICS/formoterol for symptom relief at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
17. Serum amlitelimab concentrations measured throughout the study
18. Incidence of anti-amlitelimab antibody positive response
19. Percentage of participants with treatment-emergent adverse events (TEAEs), including local reactions, AEs of special interest (AESIs), serious adverse events (SAEs)
20. Incidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period
21. Change from baseline in Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at Weeks 2, 4, 8, 12, 24, 36, and 60
22. Change from baseline in St. George’s Respiratory Questionnaire (SGRQ) at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
23. Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 48
24. Change from baseline in ACQ-6 score and ACQ-7 at Weeks 2, 4, 8, 12, 24, 36, 48, and 60

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 12

Locations

3 EU/EEA countries · 17 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 23 files

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

Application history

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