Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as AZD7986, Brensocatib, Brensocatib Oral Solution, Brensocatib Oral Tablet
INS1007 · 8 trials · 7 indications
To determine the participant clinical status on a 7-point ordinal scale, minimum value 1, maximum value 7. Higher values indicate a worse outcome: 1. Not hospitalised, no limitations on activities 2. Not hospitalised, limitation on activities; 3. Hospitalised, not requiring supplemental oxygen; 4. Hospitalised, requiring supplemental oxygen; 5. Hospitalised, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO) 7. Death.
PE was defined as having 3 or more of these symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis. A severe pulmonary exacerbation was that required intravenous (IV) antibacterial drug treatment and/or hospitalization. A minimum of 14 days must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 14 days from the prior exacerbation was not considered a new exacerbation. Independent adjudication committee with pulmonary physicians adjudicated reported PE events to see if they fulfil the protocol definition. The rate of PE was analyzed using the negative binomial model.
A TEAE is defined as any adverse event (AE) that occurred after the first dose of study investigational medicinal product (IMP) and within 28 days after the last dose of study IMP.
Time to first pulmonary exacerbation was calculated as the number of days from the date of randomization to the date of first documentation of an exacerbation. Pulmonary exacerbation was defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis A minimum of 4 weeks must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 4 weeks from the prior exacerbation was not considered a new exacerbation. The analysis was performed using the stratified log rank test and using Kaplan Meier (KM) curves.
Comparison of the pharmacokinetics of a single dose of brensocatib in participants with hepatic impairment to that in matched healthy control participants with normal hepatic function.
Pharmacokinetics of brensocatib following a single dose will be assessed in participants with renal impairment and in healthy participants.
Determination of the safety and tolerability of a single dose of brensocatib in participants with impaired renal function and in healthy participants.
Determination and comparison of the safety and tolerability of INS1007 following single and multiple dose administration in Japanese and Caucasian participants.
Comparison of the pharmacokinetics of single and multiple doses of INS1007 in Japanese and Caucasian participants.
| Arm | Type | Description |
|---|---|---|
| Brensocatib | EXPERIMENTAL | Brensocatib oral tablet, 25mg once per day for 28 days |
| Placebo | PLACEBO_COMPARATOR | Placebo oral tablet, 25mg once per day for 28 days |
| Brensocatib 10 milligrams (mg) | EXPERIMENTAL | Participants will receive brensocatib 10 mg, tablets orally, once daily, for 52 weeks. |
| Brensocatib 25 mg | EXPERIMENTAL | Participants will receive brensocatib 25 mg, tablets orally, once daily, for 52 weeks. |
| Brensocatib 40 mg | EXPERIMENTAL | Participants will receive brensocatib 40 mg tablet, orally, QD for 24 weeks along with mometasone furoate nasal spray (MFNS) by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance. |
| Brensocatib 10 mg | EXPERIMENTAL | Participants will receive brensocatib 10 mg tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance. |
| Cohort 1: Brensocatib | EXPERIMENTAL | Healthy participants with normal hepatic function will receive single oral dose of brensocatib on Day 1 under fasted conditions. Healthy participants will be matched within the protocol criteria to one or more participants with hepatic impairment. |
| Cohort 2: Brensocatib | EXPERIMENTAL | Participants with mild hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 3: Brensocatib | EXPERIMENTAL | Participants with moderate hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 4: Brensocatib | EXPERIMENTAL | Participants with severe hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 1 (Mild Impairment): Brensocatib | EXPERIMENTAL | Participants with mild renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 2 (Moderate Impairment): Brensocatib | EXPERIMENTAL | Participants with moderate renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 3 (Severe Impairment): Brensocatib | EXPERIMENTAL | Participants with severe renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 4 (Normal): Brensocatib | EXPERIMENTAL | Healthy participants with normal renal function will receive single oral dose of brensocatib on Day 1 under fasted conditions. Healthy participants will be matched within the protocol criteria to one or more participants with renal impairment. |
| Part A: Cohort 1 (Dose 1) | EXPERIMENTAL | Japanese and Caucasian participants will receive INS1007 at Dose 1 or matching placebo, orally, once on Day 1, and Day 4 through Day 30 in Part A under fasted conditions. |
| Part A: Cohort 2 (Dose 2) | EXPERIMENTAL | Japanese and Caucasian participants will receive INS1007 at Dose 2 or matching placebo, orally, once on Day 1, and Day 4 through Day 30 in Part A under fasted conditions. |
| Part A: Cohort 3 (Dose 3) | EXPERIMENTAL | Japanese and Caucasian participants will receive INS1007 at Dose 3 or matching placebo, orally, up to Day 30 in Part A under fasted conditions. Enrollment will commence in this cohort once the safety and tolerability data in Cohort 2 is deemed acceptable by the principal investigator (PI) and the Sponsor's medical monitor. |
| Part B: Treatment Sequence 1 | EXPERIMENTAL | Japanese and Caucasian participants will receive INS1007 at the dose established in Part A after a high-fat and high-calorie breakfast on Day 1 followed by a dose established in Part A on Day 8 under fasted conditions in Part B of the study. |
| Part B: Treatment Sequence 2 | EXPERIMENTAL | Japanese and Caucasian participants will receive INS1007 at the dose established in Part A under fasted conditions on Day 1 followed by dose established in Part A on Day 8 after a high-fat and high-calorie breakfast in Part B of the study. |
| Name | Type | Description |
|---|---|---|
| Brensocatib | DRUG | Selective, competitive, and reversible inhibitor of DPP1 |
| Placebo | DRUG | Matched placebo |
| Brensocatib 10 mg | DRUG | Oral tablet. |
| Brensocatib 25 mg | DRUG | Oral tablet. |
| Mometasone furoate nasal spray (MFNS) | DRUG | Nasal spray suspension. |
| INS1007 | DRUG | Oral tablets. |
Inclusion Criteria: 6.1. Inclusion criteria • Male or female * ≥16 years of age * SARS-CoV-2 infection (clinically suspected+ or laboratory confirmed\*). * Admitted to hospital as in-patient less than 96 hours prior to randomisation\^ * Illness of any duration, and at least one of the following: ...
INS1007 is an investigational small molecule developed by Insmed Incorporated. It has been studied in a Phase 1 clinical trial in healthy adult volunteers, including Japanese and Caucasian participants. Insmed is developing the compound, and its clinical program remains at the early Phase 1 stage.
INS1007 targets dipeptidyl peptidase 1, an enzyme. By acting on this enzyme target, INS1007 is designed as a small molecule therapeutic. Dipeptidyl peptidase 1 inhibition is the mechanism associated with this investigational compound being developed by Insmed Incorporated.
INS1007 is being developed by Insmed Incorporated, which trades on the Nasdaq under the ticker INSM. Insmed is the sponsor of the clinical program for this investigational small molecule. The company holds the development rights for INS1007 as part of its pipeline.
INS1007 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. The Phase 1 program has completed one trial, and no active trials are currently listed for the compound.
INS1007 has been evaluated in one completed Phase 1 trial, NCT05927597, titled A Study of the Safety, Pharmacokinetics, and Pharmacodynamics of INS1007 in Healthy Japanese and Caucasian Participants. The randomized, double-blind, controlled study enrolled 82 healthy adult volunteers in the United States.