A Study Evaluating the Efficacy and Safety of Povorcitinib (INCB054707) in Adults With Inadequately Controlled Moderate to Severe Asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

27 Jun 2024 → ongoing

Decision date (initial)

2024-05-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-502570-16-01

ClinicalTrials.gov

NCT05851443

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate the effect of 3 dosing regimens of povorcitinib on pulmonary function

Secondary objectives 1

1. To evaluate the effect of povorcitinib on asthma exacerbations

Conditions and MedDRA coding

Treatment of patients with inadequately controlled moderate to severe asthma

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Ability to comprehend and willingness to sign a written ICF for the study.
2. Women and men 18 to 65 years of age at the time of signing the ICF.
3. Physician-diagnosed asthma requiring treatment with medium- to high-dose ICS-LABA for at least 12 months prior to screening.
4. Documented treatment with a stable daily dose of medium-dose or high-dose ICS and a LABA for at least 3 months prior to screening (see Appendix F of the Protocol).
5. Agreement to use a medium- to high-dose ICS-LABA at a stable dose from screening through the duration of the study (see Appendix F of the Protocol).
6. Pre-BD FEV1 < 80% predicted according to central overread value at Visit 2.
7. Documented historical post-BD reversibility of FEV1 ≥ 12% and ≥ 200 mL in FEV1 within 12 months prior to screening OR Post-BD reversibility of FEV1 ≥ 12% and ≥ 200 mL in FEV1 according to central overread value at Visit 2.
8. At least 2 documented asthma exacerbations within 12 months prior to screening but not within the past 4 weeks prior to screening (see Protocol Section 8.1.6.2).
9. ACQ-6 ≥ 1.5 at screening.
10. Agreement to use contraception (see Appendix A of the Protocol).
11. Willing and able to comply with the study protocol and procedures.
12. Negative urine pregnancy test (WOCBP only).
13. Inclusion Criteria No. 13 described in Protocol Section 5.1 “Inclusion Criteria”.
14. Minimum compliance with ICS-LABA doses as captured in the daily eDiary during the run-in period by having at least any 11 morning and/or any 11 evening dosing days completed in the last 14 days prior to D1/BL.
15. Pre-BD FEV1 < 80% predicted according to central overread value at either Visit 3 or D1/BL.
16. ACQ-6 ≥ 1.5 at D1/BL.
17. Fulfilment of at least 1 of the following conditions over the 7 days prior to D1/BL: a. > 2 days with a daytime or nighttime symptom score ≥ 1. b. Rescue medication use on > 2 days. c. ≥ 1 nocturnal awakening due to asthma.

Exclusion criteria 24

1. Experience 1 asthma exacerbation during screening/run-in. (see Section 5.4.1 of the protocol).
2. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 4 weeks prior to screening.
3. A screening 12-lead ECG that demonstrates clinically significant abnormalities requiring treatment or that is indicative of serious underlying heart disease or criteria associated with QT/QTcF abnormalities.
4. Experience more than 1 asthma exacerbation during screening/run-in.
5. Inability to use acceptable inhaler technique or to perform PEF and spirometry assessments.
6. Maintenance use of asthma controllers other than ICS-LABA (see Section 6.6.7 of the protocol).
7. Receipt or initiation of medical treatment or procedures used for asthma management.
8. Have undergone bronchial thermoplasty.
9. Current smokers or participants with a smoking history of ≥ 10 pack-years and participants using vaping products, including electronic cigarettes. Note: Former smokers with a smoking history of <10 pack-years and users of vaping or e-cigarette products must have stopped for at least 6 months prior to screening to be eligible.
10. At the screening visit, any of the laboratory abnormalities defined in Table 7 of the protocol.
11. Evidence of infection with Mycobacterium tuberculosis (ie, TB) as defined in Section 8.3.5.2 of the protocol.
12. Women who are pregnant (or who are considering pregnancy) or breastfeeding.
13. Active HIV or acquired immunodeficiency syndrome. Active HIV is defined as a confirmed positive anti-HIV antibody test (see Section 8.3.5.3 of the protocol).
14. Exclusion Criteria No. 9 described in Protocol Section 5.2 “Exclusion Criteria”.
15. Undergone significant trauma or major surgery (per investigator's assessment) within 30 days prior to screening.
16. Planned or expected major surgery during the initial 24 weeks of treatment with study drug (ie, during the PC period of the study).
17. History of clinically significant (per investigator's judgment) drug or alcohol abuse within 6 months prior to screening.
18. Exclusion Criteria No. 15 described in Protocol Section 5.2 “Exclusion Criteria”.
19. Exclusion Criteria No. 16 described in Protocol Section 5.2 “Exclusion Criteria”.
20. Concurrent enrollment in another clinical study.
21. Evidence of HBV or HCV infection or risk of reactivation (see Section 8.3.5.4 of the protocol).
22. Known hypersensitivity or severe reaction to povorcitinib or excipients of povorcitinib (refer to the IB) and/or other products in the same class.
23. Any condition, laboratory result, or result of screening assessments that would, in the investigator's and sponsor's (or designee's) judgment, interfere with full participation in the study, including administration of study drug and attending required study visits, pose a significant risk to the participant, or interfere with interpretation of study data.
24. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change from baseline in pre-BD FEV1 at Week 24

Secondary endpoints 3

1. Number of asthma exacerbations during the PC period, defined as a worsening of asthma that leads to any of the following: − Use of systemic CS for at least 3 consecutive days; a single depo-injectable dose of CS will be considered equivalent to a 3-day course of systemic CS
2. An emergency department or urgent care visit (defined as evaluation and treatment for < 24 hours in an emergency department or urgent care center) due to asthma that required use of systemic CS (as noted above)
3. An inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥ 24 hours) due to asthma

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Third parties 2

Locations

3 EU/EEA countries · 14 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 51 files

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

Application history

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