A Phase 2 study to evaluate the efficacy and safety of RPT193 in adults with moderate-to-severe T2-high asthma who are partially controlled on inhaled corticosteroid and long-acting beta 2 agonist therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rapt Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

26 Nov 2023 → 22 Jun 2024

Decision date (initial)

2023-10-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

RAPT Therapeutics Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To evaluate the effect of 400 mg RPT193 compared with placebo on loss of asthma control (LOAC) in adults with T2-high partially controlled asthma on inhaled corticosteroid (ICS) plus long-acting beta 2 agonists (LABA) over 14 weeks

Secondary objectives 1

1. To evaluate the safety and tolerability of RPT193 administered orally To evaluate the effect of RPT193 on time to a LOAC event(s) To evaluate the effect of RPT193 on lung function in subjects with asthma To evaluate the effect of RPT193 on asthma control

Conditions and MedDRA coding

Asthma

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Male or female (biologic sex) adult aged 18 to 75 years, inclusive, at the time of consent.
2. Physician diagnosis of asthma for ≥ 6 months based on GINA guidelines (GINA 2022).
3. Body mass index (BMI) ≥ 18 kg/m2
4. Pre-bronchodilator FEV1 of > 40% and < 80% at the Screening visit and > 40% and < 85% at the Baseline (Day 1) visit. The screening spirometry can be repeated once during the screening period at the discretion of the Investigator if it is nearly outside of eligibility criteria and in the Investigator's judgment there may be the potential for spirometry values aligned with eligibility based on subject's historic data.
5. Subjects with evidence of reversible airway obstruction, as defined by either of the following: a. ≥ 12% and 200 mL increase in FEV1 after administration of up to 4 inhalations (up to albuterol during Screening, or documented history of a reversibility test that met these criteria within 12 months prior to Screening. b. Absolute relative change in FEV1 ≥12% and 200 mL over 2 measurements documented by repeat spirogram over the previous year and within 4 months after initiation of treatment with ICS with or without LABA (Wechsler 2019).
6. Subject has a history of at least 1 of either of the following in the past 12 months: a. Treatment with a systemic corticosteroid (either orally for ≥ 3 days or parenterally) OR b. Hospitalization or an emergency room visit for worsening asthma.
7. Medium- or high-dose equivalent ICS therapy (as defined by GINA 2022 guidelines) in combination with LABA at Screening with a stable dose in the 8 weeks prior to Screening and at the Baseline visit. Note: Subjects will receive standardized therapy equivalent to the dose of ICS the subject is taking at Screening.
8. Questionnaire score of ≥ 1.5 and < 3.5 at Screening and ≥ 1.25 and < 3.5 at Baseline.
9. Absolute eosinophil count ≥ 300/µL within the last 6 months prior to Screening OR FeNO ≥ 25 ppb at Screening.
10. Women of childbearing potential with a negative serum pregnancy test at Screening and negative urine pregnancy test at the Baseline (Day 1) visit.
11. For women of childbearing potential involved in any sexual intercourse that could lead to pregnancy: the subject must agree to use a highly effective contraceptive method from at least 4 weeks prior to Baseline (Day 1) until at least 30 days after the last investigational product (IP) administration. Highly effective contraceptive methods include hormonal contraceptives (eg, combined oral contraceptive, patch, vaginal ring, injectable, or implant), intrauterine devices or intrauterine systems, vasectomized partner(s), tubal ligation or double barrier methods of contraception (eg, male condom with cervical cap, male condom with diaphragm, and male condom with contraceptive sponge) in conjunction with spermicide..
12. Female subject agrees to not have egg retrieval during the study and for 30 days after the last IP administration.
13. For male subject involved in any sexual intercourse that could lead to pregnancy, subject must agree to use 1 of the highly effective contraceptive methods listed in Inclusion Criterion #11 from Baseline (Day 1) until at least 90 days after the last IP administration. If the female partner of a male subject uses any of the hormonal contraceptive methods listed above, this contraceptive method should be used by the female partner from at least 4 weeks before Baseline (Day 1) until at least 90 days after the last IP administration.
14. Male subject agrees not to donate sperm during the study and for 90 days after the last IP administration.
15. Subject is willing to participate and is capable of giving informed consent. Note: Consent must be obtained prior to any study-related procedures.

Exclusion criteria 10

1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.
2. History of smoking per age group as follows (see also Exclusion Criterion #3): a. < 30 years old: Smoked for ≥ 5 pack-years.* b. 30 to 39 years old (inclusive): Smoked for ≥10 pack-years c. ≥40 years old: Smoked for ≥ 15 pack-years.
3. Active use of any inhalant >1 time weekly in the past year including: a. Active smoking of conventional tobacco, marijuana (in any inhaled form) or other drugs, or vaping of e-cigarettes or e-devices. b. Other forms of tobacco including: 1 cigarette, 1 hookah or shisha session, 1 cigar, or 1 pipe.
4. Subject has any serious and/or uncontrolled medical condition (including cognitive impairment, alcohol/drug abuse, or signs/symptoms suspicious for a serious disease) or laboratory abnormality that would place subject's safety at risk or interfere with study participantion, as juddged by the Investigator.
5. Conditions that may mimic asthma (eg, vocal cord dysfunction, hyperventilation, panic attacks, cardiac asthma, uncontrolled gastroesophageal reflux disease).
6. Subject has a history of severe COVID-19 that required intensive care unit (ICU) admission or assisted ventilation (including both invasive and non-invasive) in the 6 weeks before screening and did not return to their previous (pre-COVID-19 infection) respiratory status.
7. Subject has any of the following serious and/or uncontrolled medical conditions: a. Chronic obstructive pulmonary disease (COPD). b. Idiopathic pulmonary fibrosis (IPF). c. Subjects with uncontrolled diabetes (eg, hemoglobin A1c [HbA1c] ≥ 9%). d. Stage III or IV cardiac failure according to the New York Heart Association classification. e. Acute myocardial infarction, clinically significant arrythmia, or indications of serious underlying heart disease)/vital signs abnormality that, in the opinion of the Investigator would be indicative of an underlying medical condition, puts the subject at undue risk, and/or interfere with interpretation of study results. f. Severe renal conditions (eg, subjects on dialysis). g. Active autoimmune disease (eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease). h. Subject has a history of a clinically significant systemic infection or serious respiratory infection requiring parenteral antibiotic treatment within 4 weeks prior to the Baseline (Day 1) visit, or oral therapy within 2 weeks prior to the Baseline (Day 1) visit. i. Subject has a diagnosis of, is suspected of having, or is at high risk for an endoparasitic infection unless clinical and laboratory assessment have ruled out active endoparasitosis prior to the Baseline (Day 1) visit. j. Subjects with moderate-to-severe hepatic impairment (ie, Child-Pugh score ≥7) k. Subject has a history of a life-threatening asthma exacerbation in the last 5 years including but not limited to requirements for intubation and ventilation.
8. Subject has had a major surgery in the past 8 weeks prior to Screening or has a major, elective surgery planned during the study.
9. Any of the following specific laboratory findings: a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN). b. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 (Modification of Diet in Renal Disease (MDRD) equation) unless considered normal for age. c. Platelet count < 75,000 cells/mm3 d. Hemoglobin < 10 g/dL. e. Absolute lymphocyte count < 800 cells per mm3 f. Absolute neutrophil count < 1500 cells per mm3
10. Please refer to Protocol for complete list of exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects who satisfy any of the following LOAC criteria: - ≥30% reduction in morning PEF from baseline on 2 consecutive days - ≥6 additional reliever inhalations of SABA in a 24-hour period relative to abseline on 2 consecutive days - Increase by a factor of 4 or more in the most recent dose of ICS - Exacerbation of asthma requiring systemic CS. - Exacerbation of asthma - related AE that requires a hospitalization or emergency room visit

Secondary endpoints 10

1. Frequency of treatment-emergent adverse events
2. Time to a LOAC event
3. Change in forced expiratory volume in 1 second (FEV1) at Day 99 (Week 14) and at each interval visit after treatment with RPT193 compared to baseline
4. Change in Questionnaire score at Day 99 (Week 14) and at each interval visit after treatment with RPT193 compared to baseline
5. Change in PEF at Day 99 (Week 14) and at each interval visit after treatment with RPT193 compared to baseline
6. Change in reliever bronchodilator use at Day 99 (Week 14) and at each interval visit after treatment with RPT193 compared to baseline
7. Change in fractional exhaled nitric oxide (FeNO) at Day 99 (Week 14) and at each interval visit after treatment with RPT193 compared to baseline
8. Change in Questionnaire at Day 99 (Week 14) and at each interval visit after treatment with RPT193 compared to baseline
9. Change in FEV1 from Day 99 to 140 (Weeks 14 to 20)
10. Change in FEV1 from Day 43 to 98 (Weeks 6 to 14)

Investigational products

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

Test 1

Placebo 1

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rapt Therapeutics Inc.

Sponsor organisation

Rapt Therapeutics Inc.

Address

561 Eccles Avenue

City

South San Francisco

Postcode

94080-1906

Country

United States

Scientific contact point

Organisation

Rapt Therapeutics Inc.

Contact name

Laurence Cheng, MD

Public contact point

Organisation

Rapt Therapeutics Inc.

Contact name

Laurence Cheng, MD

Third parties 7

Locations

3 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

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 3 files

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

Application history

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