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One Year Study to Evaluate the Long-term Safety and Tolerability of Dupilumab in Pediatric Patients with Asthma who Participated in a Previous Dupilumab Asthma Clinical Study

Assessment of the Safety and Efficacy of Dupilumab in Children with Asthma (Liberty Asthma Excursion)

378

For main-study excluded Japan: The mean (standard deviation [SD]) age of the exposed population at Week 0 was 9.9 (1.6) years. Approximately 64.1% of participants were male and 35.9% were female. Most participants (89.3%) were Caucasian/White. For Japan sub-study: The mean (SD) age of the enrolled population was 9.69 (1.11) years. Nine (69.2%) participants were males, and 4 (30.8%) participants were females.

For main-study excluded Japan: - Enrolled and treated: 365 (Placebo-Dupilumab: 125, Dupilumab-Dupilumab: 240) - Completed the study treatment period: 350 (Placebo-Dupilumab: 122, Dupilumab-Dupilumab: 228) - Completed the study period: 346 (Placebo-Dupilumab: 118, Dupilumab-Dupilumab: 228) A total of 365 participants were enrolled in this study (rolled over from the parent study EFC14153) and received open-label study treatment with dupilumab (at either 100 mg once every 2 weeks [q2w], 200 mg q2w, or 300 mg once every 4 weeks [q4w] based on the dosing criteria specified in the protocol). Among the 365 participants, 240 participants previously treated with dupilumab in the parent study (dupilumab-dupilumab category) continued with dupilumab treatment for up to an additional 52 weeks, and 125 participants previously on placebo in the parent study (placebo-dupilumab category) started dupilumab treatment for up to 52 weeks. For Japan sub-study: - Enrolled and exposed: 13 - Completed the study treatment period: 13 - Completed the study period: 8" A total of 13 participants were enrolled in this study and received open-label study treatment with dupilumab (at either 100 mg q2w, 200 mg q2w, or 300 mg q4w based on the dosing criteria specified in the protocol).

For main-study excluded Japan: Refer to "Outcome measures" For Japan sub-study: Overall, all (N=13) participants experienced at least 1 TEAE during the study. Four (30.8%) participants experienced at least 1 treatment emergent serious adverse event (SAE). No participants had a TEAE that led to death.

For main-study excluded Japan: Primary endpoint: Overall, 232 (63.6%) participants (85 [68.0%] in the placebo-dupilumab category and 147 [61.3%] in the dupilumab-dupilumab category) experienced at least 1 TEAE during the study. No participants had a TEAE leading to death. The incidence of treatment emergent SAEs was low, reported in 7 (1.9%) participants overall. Secondary endpoints: All efficacy endpoints in this open-label extension study were secondary endpoints. In the full analysis set of the safety population, participants treated with dupilumab for up to an additional year after the parent study demonstrated a low rate of severe asthma exacerbations with an unadjusted annualized severe exacerbation event rate of 0.118 in all exposed participants. A low rate of severe exacerbations was observed regardless of the treatment arm in the parent study (dupilumab-dupilumab or placebo-dupilumab). In the full analysis set, there was a mean improvement of +10.01% in pre-bronchodilator (BD) percent predicted FEV1 from baseline in the parent study at Week 2, which was sustained for the entire 52-week treatment period in the dupilumab-dupilumab category participants. Rapid onset in lung function improvement was observed for dupilumab treated participants in the parent study and was replicated for the placebo-dupilumab participants in this study. The mean change from baseline in the placebo-dupilumab category was +3.64% at Week 0 and +8.06% at Week 2, and this improvement was sustained over 52 weeks. There was also sustained improvement across other measures of lung function including absolute FEV1, absolute and percent predicted FVC, and percent predicted FEF 25-75%, which continued to improve over the duration of the study. For Japan sub-study: Dupilumab led to sustained improvement in lung function compared to baseline. Overall, there was a mean improvement of +7.08% in pre-BD percent predicted FEV1 from baseline at Week 12. Improvement in pre-BD percent predicted FEV1 was rapid with an onset of an improvement detected as early as Week 2 and then sustained over 52 weeks." There was also sustained improvement across other measures of lung function including absolute FEV1, FVC, and FEF 25-75%, and all of which showed continued improvement over time up to Week 52. The unadjusted annualized rate of severe asthma exacerbation events during the 52-week treatment period was 0.462.

For main-study excluded Japan: A total of 365 participants were enrolled (Placebo-Dupilumab: 125, Dupilumab-Dupilumab: 240). The results from this study support the long-term safety, tolerability, and efficacy of dupilumab in a moderate to severe pediatric asthma population. For Japan sub-study: A total of 13 participants were enrolled. The results from this study support the efficacy, safety, and tolerability of dupilumab in a Japanese pediatric population with uncontrolled moderate to severe asthma.

Yes

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

https://jrct.mhlw.go.jp/latest-detail/jRCT2041210042

Obara Kentaro

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

clinical-trials-jp@sanofi.com

Clinical Study Unit

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

+81-3-6301-3670

clinical-trials-jp@sanofi.com

Complete

Aug. 07, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

For main-study excluded Japan:
- Pediatric patients with asthma who completed the treatment in a dupilumab asthma trial (EFC14153).
- Signed written informed consent/assent.

Patients who are not able to complete their treatment in Study EFC14153 due to the COVID-19 pandemic will be allowed to enroll into Study LTS14424. Patients who enroll in LTS14424 after completing the EFC14153 End-of-study (EOS) visit should have eligibility for LTS14424 reevaluated including background medication check and laboratory assessments (including CBC with differential and basic chemistry) within 1 month prior to LTS14424 Visit 1.

For Japan sub-study:
- Signed written inform consent/assent
- Children 6 to <12 years of age, with a physician diagnosis of persistent asthma for >=12 months prior to screening
- Blood eosinophil count >=150 cells/microL or fractional exhaled nitric oxide (FeNO) >=20 parts per billion (ppb) at screening visit (Visit 0).

Participants are excluded from the study if any of the following criteria apply:
For main-study excluded Japan:
- Any chronic lung disease other than asthma (eg, cystic fibrosis, bronchopulmonary dysplasia) which may impair lung function.
-Inability to follow the procedures of the study/noncompliance (eg, due to language problems or psychological disorders).
- Patients receiving concomitant treatment or required a new concomitant treatment prohibited in the study.
- Patients or his/her parent(s)/caregiver(s)/legal guardian(s) is related to the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff thereof directly involved in the conduct of the study.
- Patients who experienced any hypersensitivity reactions to dupilumab in a previous dupilumab study, which, in the opinion of the Investigator, could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient.
- Any abnormalities or adverse events at screening (last treatment visit in the study EFC14153 will be the screening visit) that per Investigator judgment would adversely affect patient's participation in this study or would require permanent IMP discontinuation.
- For female patients who have commenced menstruating at any time during the study and are either:
- Found to have a positive urine pregnancy test, or
- Sexually active, not using an established acceptable contraceptive method.
- Planned live, attenuated vaccinations during the study.
- Patients with active autoimmune disease or patients using immunosuppressive therapy for autoimmune disease (eg, juvenile idiopathic arthritis, inflammatory bowel disease, systemic lupus erythematosus) at enrollment.

For Japan sub-study:
- Any chronic lung disease other than asthma (eg, cystic fibrosis, bronchopulmonary dysplasia) which may impair lung function.
- Inability to follow the procedures of the study/noncompliance (eg, due to language problems or psychological disorders).
- Patients receiving concomitant treatment or required a new concomitant treatment prohibited in the study at the screening and enrollment visits.
- Patients who previously have been treated with dupilumab
- Diagnosed with active parasitic infection (helminthes); suspected or high risk of parasitic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomization
- Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), despite infection resolution; or unusually frequent, recurrent, or prolonged infections, per Investigator's judgment.

Both

Asthma

Drug: Dupilumab (SAR231893/REGN668)
Pharmaceutical form: solution for injection, Route of administration: subcutaneous (sc), Doses of dupilumab will be administered every 2 weeks or every 4 weeks added to current controller medications for 52 weeks

Drug: Asthma controller therapies (incl. prednisone/prednisolone)
Pharmaceutical form: powder, or solution, or pill, Route of administration: inhaled, oral or parenteral

Drug: Asthma reliever therapies
Pharmaceutical form: powder or solution, Route of administration: inhaled

1. For main-study excluded Japan:The number of patients experiencing any treatment emergent adverse event (TEAE) [ Time Frame: From Day 1 up to Week 64 ]
The number of patients experiencing any TEAE.

2. Japan sub-study: Change from baseline in pre-bronchodilator percentage (%) predicted FEV1 at Week 12 [ Time Frame: Baseline to Week 12 ]
Change from baseline in pre-bronchodilator percentage (%) predicted forced expiratory volume in 1 second (FEV1) at week 12.

1. For main-study excluded Japan: Annualized rate of severe asthma exacerbation events during the treatment period [ Time Frame: From Day 1 up to Week 52 ]
Annualized rate of severe asthma exacerbation events during the treatment period.

2. For main-study excluded Japan: Change from baseline in % predicted FEV1 [ Time Frame: Baseline to Week 64 ]
Change from baseline in % predicted FEV1.

3. For main-study excluded Japan: Change from baseline in absolute FEV1 [ Time Frame: Baseline to Week 64 ]
Change from baseline in absolute FEV1.

4. For main-study excluded Japan: Change from baseline in FVC [ Time Frame: Baseline to Week 64 ]
Change from baseline in forced vital capacity (FVC).

5. For main-study excluded Japan: Change from baseline in FEF 25 to 75% [ Time Frame: Baseline to Week 64 ]
Change from baseline in forced expiratory flow (FEF) 25-75%.

6. For main-study excluded Japan: Serum dupilumab concentrations [ Time Frame: From Day 1 up to Week 64 ]
Serum dupilumab concentrations.

7. For main-study excluded Japan: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab [ Time Frame: From Day 1 up to Week 64 ]
Incidence of treatment-emergent ADA against dupilumab.

8. For main-study excluded Japan: IBlood eosinophil counts [ Time Frame: From Day 1 up to Week 64 ]
Blood eosinophil counts.

9. For main-study excluded Japan: Serum total IgE [ Time Frame: From Day 1 up to Week 64 ]
Serum total IgE.

10. Japan sub-study: Annualized rate of severe asthma exacerbation events during the treatment period [ Time Frame: From Day 1 up to Week 52 ]
Annualized rate of severe asthma exacerbation events, during the treatment period.

11. Japan sub-study: Change from baseline in pre-bronchodilator % predicted FEV1 at Weeks 2, 4, 8, 24, 52, and 64 [ Time Frame: Baseline to Week 2, 4, 8, 24, 52 and 64 ]
Change from baseline in pre-bronchodilator % predicted FEV1 at Weeks 2, 4, 8, 24, 52, and 64.

12. Japan sub-stud: Change from baseline in absolute FEV1 [ Time Frame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64 ]
Change from baseline in absolute FEV1.

13. Japan sub-study: Change from baseline in FVC [ Time Frame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64 ]
Change from baseline in FVC.

14. Japan sub-study: Change from baseline in FEF 25-75% [ Time Frame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64 ]
Change from baseline in FEF 25-75%.

15. Japan sub-study: Change from baseline in ACQ-IA [ Time Frame: Baseline to Week 2, 4, 8, 12, 24, 36, 52, and 64 ]
Change from baseline in Asthma Control Questionnaire-Interviewer Administered (ACQ-IA).

16. Japan sub-study: The number of patients experiencing any TEAEs [ Time Frame: From Day 1 up to Week 64 ]
The number of patients experiencing any TEAEs.

17. Japan sub-study: Serum dupilumab concentrations [ Time Frame: From Day 1 up to week 64 ]
Serum dupilumab concentrations.

18. Japan sub-study: Incidence of treatment-emergent ADA against dupilumab [ Time Frame: From Day 1 up to Week 64 ]
Incidence of treatment-emergent ADA against dupilumab.

19. Japan sub-study: Serum total immunoglobulin E (IgE) [ Time Frame: From Day 1 up to Week 64 ]
Serum total immunoglobulin E (IgE).

20. Japan sub-study: Change from Baseline in FeNO [ Time Frame: Baseline to Weeks 2, 4, 8, 12, 24, 52, and 64 ]
Change from Baseline in Fractional Exhaled Nitric Oxide (FeNO).

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June. 08, 2021

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