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
- Trial ID
- 2022-502854-16-00
- Protocol
- RPT193-03
- Sponsor
- Rapt Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2 study is to evaluate the effect of 400 mg **RPT193** compared with placebo on the loss of asthma control (LOAC) in adults with T2-high partially controlled asthma who are on inhaled corticosteroid (ICS) plus long-acting beta 2 agonists (LABA) over a period of 14 weeks. This is clinically relevant as it aims to determine the potential of RPT193 to improve asthma management in patients who are not fully controlled with standard therapy, potentially reducing exacerbations and improving quality of life.
Secondary objectives include: - Evaluating the safety and tolerability of RPT193 when administered orally. - Assessing the effect of RPT193 on the time to a LOAC event(s). - Evaluating the impact of RPT193 on lung function in subjects with asthma. - Assessing the effect of RPT193 on asthma control. These objectives are crucial for understanding the broader implications of RPT193 on patient health and its potential role in asthma treatment regimens.
Participants
The clinical trial involves a total of **29 participants** diagnosed with **asthma**, specifically targeting adults aged 18 to 75 years. The study population includes both male and female subjects, with a focus on individuals with T2-high partially controlled asthma who are currently on inhaled corticosteroid (ICS) plus long-acting beta 2 agonists (LABA) therapy. Participants were selected based on specific criteria, including a physician diagnosis of asthma for at least six months, a body mass index (BMI) of 18 kg/m² or higher, and evidence of reversible airway obstruction. The trial also considers lifestyle factors such as the stability of asthma medication doses and recent asthma-related medical history, including systemic corticosteroid treatment or hospital visits. The study does not exclude based on gender, and both male and female subjects are included, with considerations for contraceptive use and pregnancy testing for women of childbearing potential. The trial population is characterized by a history of asthma management and a commitment to maintaining current treatment regimens throughout the study duration.
Plans and Procedures
The clinical trial is designed 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. This is a Phase 2, randomized, double-blind, placebo-controlled trial. The primary objective is to assess the effect of 400 mg RPT193 compared with placebo on the loss of asthma control over a period of 14 weeks. The trial is expected to conclude by December 2024, with recruitment having commenced in September 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, asthma diagnosis, and current treatment regimen. The baseline visit (Day 1) will mark the start of the treatment period, during which participants will receive either RPT193 or a placebo. Follow-up visits will occur at regular intervals to monitor the participants' health, assess asthma control, and record any adverse events. The end-of-study visit will occur at the conclusion of the 14-week treatment period, where final assessments will be conducted.
The expected length of participant involvement is approximately 14 weeks, with conditions for early termination including significant adverse events or a decision by the investigator that continued participation is not in the participant's best interest. The trial will measure primary endpoints such as the proportion of subjects experiencing a loss of asthma control, defined by criteria including a reduction in morning peak expiratory flow or increased use of reliever inhalations. Secondary endpoints will include the frequency of treatment-emergent adverse events and changes in forced expiratory volume, among others.
Treatment
The clinical trial involves the administration of **RPT193**, an experimental medication formulated as a tablet. The active substance in RPT193 is 3-[(3R)-3-[1-[5-chloro-4-[[(1R)-1-(2,4-dichlorophenyl)ethyl]amino]-6-methylpyrimidin-2-yl]azetidin-3-yl]piperidin-1-yl]-1-methylcyclobutane-1-carboxylic acid. This chemical compound is administered orally at a dosage of 400 mg per day, with a maximum treatment period of 14 days. The total maximum dose over the treatment period is 39,200 mg. Participant compliance with the dosing schedule is monitored throughout the trial.
In addition to the experimental treatment, the study includes the use of **Flixotide 50 micrograms Evohaler**, a pressurised inhalation suspension containing **fluticasone propionate**. This non-experimental treatment is administered via inhalation, with a maximum daily dose of 1000 micrograms and a total maximum dose of 19,600 micrograms over a 5-day period. This medication serves as a standard-of-care therapy for participants with moderate-to-severe T2-high asthma.
Another non-experimental treatment used in the study is **Seretide Diskus 50 Mikrogramm/250 Mikrogramm/Dosis**, an inhalation powder pre-dispensed formulation containing a combination of **fluticasone propionate** and **salmeterol**. This treatment is administered via inhalation, with a maximum daily dose of 1200 micrograms and a total maximum dose of 84,000 micrograms over a 10-day period. This combination therapy is part of the standard treatment regimen for asthma management in the trial.
The study also includes the use of **Ventolin Evohaler 100 micrograms Pressurised Inhalation Suspension**, which contains **salbutamol sulfate**. This medication is administered via inhalation, with a maximum daily dose of 10 mg and a total maximum dose of 1680 mg over a 24-day period. It is used as a rescue medication for participants experiencing acute asthma symptoms during the trial.
A placebo, in the form of a tablet without an active substance, is also utilized in the study to evaluate the efficacy of RPT193. The placebo is administered in a manner consistent with the experimental treatment to maintain blinding and ensure the integrity of the trial results.
Efficacy
The efficacy of the investigational product RPT193 in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the proportion of subjects experiencing a **loss of asthma control (LOAC)**, defined by criteria such as a ≥30% reduction in morning peak expiratory flow (PEF) from baseline on two consecutive days, an increase in reliever inhalations, or exacerbations requiring systemic corticosteroids or hospitalization.
Secondary endpoints include the frequency of treatment-emergent adverse events, time to a LOAC event, and changes in several parameters from baseline to Day 99 (Week 14) and at each interval visit. These parameters include forced expiratory volume in 1 second (FEV1), PEF, reliever bronchodilator use, fractional exhaled nitric oxide (FeNO), and questionnaire scores. Additionally, changes in FEV1 will be monitored from Day 99 to 140 (Weeks 14 to 20) and from Day 43 to 98 (Weeks 6 to 14).
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female (biologic sex) adult aged 18 to 75 years, inclusive, at the time of consent.
- Physician diagnosis of asthma for ≥ 6 months based on GINA guidelines (GINA 2022).
- Body mass index (BMI) ≥ 18 kg/m2
- 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.
- 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).
- 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.
- 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.
- Questionnaire score of ≥ 1.5 and < 3.5 at Screening and ≥ 1.25 and < 3.5 at Baseline.
- Absolute eosinophil count ≥ 300/µL within the last 6 months prior to Screening OR FeNO ≥ 25 ppb at Screening.
- Women of childbearing potential with a negative serum pregnancy test at Screening and negative urine pregnancy test at the Baseline (Day 1) visit.
- 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..
- Female subject agrees to not have egg retrieval during the study and for 30 days after the last IP administration.
- 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.
- Male subject agrees not to donate sperm during the study and for 90 days after the last IP administration.
- 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
- Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.
- 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.
- 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.
- 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.
- Conditions that may mimic asthma (eg, vocal cord dysfunction, hyperventilation, panic attacks, cardiac asthma, uncontrolled gastroesophageal reflux disease).
- 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.
- 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.
- Subject has had a major surgery in the past 8 weeks prior to Screening or has a major, elective surgery planned during the study.
- 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
- Please refer to Protocol for complete list of exclusion criteria.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 16 Sept 2023 | 24 |
 Czechia | Not Recruiting | 16 Sept 2023 | 16 |
 Poland | Not Recruiting | 16 Sept 2023 | 31 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
RPT193 | Test | TABLET | ORAL | 400 | 14 | PRD10460206 |
Flixotide 50 micrograms Evohaler | Other | PRESSURISED INHALATION, SUSPENSION | INHALATION | 1000 | 5 | PRD355141 |
Seretide Diskus 50 Mikrogramm/250 Mikrogramm/Dosis, einzeldosiertes Pulver zur Inhalation | Other | EINZELDOSIERTES PULVER ZUR INHALATION | INHALATION | 1200 | 10 | PRD2175351 |
Flixotide 250 micrograms Evohaler | Other | PRESSURISED INHALATION, SUSPENSION | INHALATION | 1000 | 5 | PRD448815 |
Flixotide 125 micrograms Evohaler | Other | PRESSURISED INHALATION, SUSPENSION | INHALATION | 1000 | 5 | PRD448818 |
Ventolin Evohaler 100 micrograms Pressurised Inhalation Suspension | Other | PRESSURISED INHALATION SUSPENSION | INHALATION | 10 | 24 | PRD451876 |
Tablet without active substance | Placebo | N/A | — | — | — | N/A |
Seretide Diskus 50 Mikrogramm/100 Mikrogramm/Dosis, einzeldosiertes Pulver zur Inhalation | Other | EINZELDOSIERTES PULVER ZUR INHALATION | INHALATION | 1200 | 10 | PRD2072102 |
Seretide Diskus 50 Mikrogramm/500 Mikrogramm/Dosis, einzeldosiertes Pulver zur Inhalation | Other | EINZELDOSIERTES PULVER ZUR INHALATION | INHALATION | 1200 | 10 | PRD2175688 |