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Business decision pending resolution of clinical hold with FDA
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To evaluate the pharmacokinetics (PK) of SPR719, the active moiety, generated from the orally (po) administered SPR720 prodrug in a patient population with nontuberculous mycobacteria pulmonary disease (NTM-PD)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SPR720 low dose | Experimental | SPR720 500 mg administered orally once daily for 28 days. |
|
| SPR720 high dose | Experimental | SPR720 1000 mg administered orally once daily for 28 days. |
|
| Placebo | Placebo Comparator | Placebo administered orally once daily for 28 days |
|
| Standard of Care (SOC) | Active Comparator | Standard of Care regimen per the Investigator's discretion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SPR720 | Drug | Capsules for oral administration |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of SPR719 | SPR719 is the active moiety of the prodrug SPR720. Blood samples were planned to be taken at a subset of study sites in order to conduct intensive pharmacokinetic (PK) evaluation. | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
| Time to Reach Maximum Plasma Concentration (Tmax) of SPR719 | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose | |
| Area Under the Concentration-time Curve From Zero to Tau, Where Tau is the Dosing Interval (AUC0-tau) for SPR719 | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose | |
| Accumulation Ratio of SPR719 | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational/experimental) product, whether related to this product or not. This includes any newly occurring event or previous condition that has increased in severity or frequency since starting active or randomized treatment. The Investigator assessed the intensity for each AE reported during the study using the latest version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, as Mild, Moderate, Severe, Life-threatening, or Death. |
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Inclusion Criteria:
Has a diagnosis of NTM-PD due to MAC
Had at least 1 prior positive culture (sputum or bronchoalveolar lavage) positive for MAC in the previous 6 months
Has an induced sputum culture at screening positive for MAC by at least one of the following methods performed by the microbiology laboratory: quantitative culture on solid agar or growth on liquid media (MGIT)
Is either treatment naïve and has not received any prior treatment for MAC, OR if previously treated for MAC, has culture evidence of persistent, recurrent, or relapsed disease and has been off therapy for at least 6 months
In the opinion of the Investigator, is ready to initiate treatment (treatment naïve) or reinitiate treatment (previously treated) within the next 3 months, and for whom a delay, in order to participate in a placebo-controlled clinical trial, is considered reasonable and clinically acceptable
Had clinical signs and symptoms within the 6 weeks before the date of consent that are consistent with NTM-PD with at least two of the following:
Has a measured forced expiratory volume in 1 second (% predicted FEV1) ≥30% on pulmonary function test within 3 months prior to consent
Has a chest radiograph (CXR) or computed tomography (CT) scan within 6 months prior to consent with findings consistent with NTM-PD. If no CXR or CT scan is available, a CXR or CT scan should be performed at screening to confirm eligibility.
Other inclusion criteria per protocol
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Melnick, MD | Spero Therapeutics Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical Facility | Altamonte Springs | Florida | 32701 | United States | ||
| Medical Facility |
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A total of 90 participants were planned to be enrolled across 4 treatment groups. As a result of early discontinuation of the study, only 2 treatment groups were initiated, with 1 participant enrolled in each group.
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| ID | Title | Description |
|---|---|---|
| FG000 | SPR720 500 mg | SPR720 500 mg administered orally once daily for 28 days. |
| FG001 | Placebo | Placebo administered orally once daily for 28 days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 17, 2020 |
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Treatment Arms 1 to 3 are masked while Treatment Arm 4 is open-label
| Placebo |
| Drug |
Capsules for oral administration |
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| Open-label Standard of Care | Drug | Standard of Care regimen is at the Investigator's discretion; recommended 2-drug or 3-drug SOC, consisting of either:
Optional rifampin 600 mg or rifabutin 300 mg orally once daily may be added to the SOC regimen for up to 28 days. |
|
| From first dose of study drug (Day 1) up to 28 days after last dose (56 days) |
| Number of Participants With Clinically Meaningful Change in Physical Examination Findings | Full physical examination were conducted on Day 1 and 28 days after last dose (Day 56) and included, at a minimum, assessment of the following systems: skin, head, ears, eyes, nose and throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system. Symptom-directed physical examinations were conducted at study visits on Days 7, 14, 21, and 28. | Days 1, 7, 14, 21, 28, and 56 |
| Number of Participants Who Received Any Concomitant Medication During the Study | Day 1 to Day 56 |
| Changes From Baseline in Laboratory Tests | Days 1, 7, 14, 21, 28, and 56 |
| Number of Participants With Clinically Significant Out-of-normal Range Laboratory Tests | Clinical laboratory tests included serum chemistry, hematology, coagulation tests, and urinalysis. The investigator determined whether any changes in laboratory values were clinically significant based on the condition of the participant and the extent and duration of the deviation from the reference range. | Days 1, 7, 14, 21, 28, and 56 |
| Shifts From Baseline in Selected Laboratory Tests Using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Shift Categories | Days 1, 7, 14, 21, 28, and 56 |
| Changes From Baseline in Vital Sign Measurements | Vital signs measurements included systolic and diastolic blood pressure, pulse, temperature, and respiratory rate. | Days 1, 7, 14, 21, 28, and 56 |
| Number of Participants With Clinically Significant Abnormal Electrocardiogram Findings | Standard 12-lead electrocardiogram (ECG) assessments included heart rate, cardiac rhythm, PR interval, RR interval, QRS interval, QT interval and QTC interval. Clinical significance was determined by the investigator. | Days 1, 14, 28, and 56 |
| Atlantis |
| Florida |
| 33462 |
| United States |
| Medical Facility | Clearwater | Florida | 33765 | United States |
| Medical Facility | Kissimmee | Florida | 34746 | United States |
| Medical Facility | West Palm Beach | Florida | 33407 | United States |
| Medical Facility | Charlotte | North Carolina | 28207 | United States |
| Medical Facility | Mooresville | North Carolina | 28117 | United States |
| Medical Facility | Winston-Salem | North Carolina | 27103 | United States |
| Medical Facility | Pittsburgh | Pennsylvania | 15213 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | SPR720 500 mg | SPR720 500 mg administered orally once daily for 28 days. |
| BG001 | Placebo | Placebo administered orally once daily for 28 days. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Plasma Concentration (Cmax) of SPR719 | SPR719 is the active moiety of the prodrug SPR720. Blood samples were planned to be taken at a subset of study sites in order to conduct intensive pharmacokinetic (PK) evaluation. | No participants were enrolled at study sites that were conducting intensive PK evaluations. | Posted | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
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| ||||||||||||||||||||
| Primary | Time to Reach Maximum Plasma Concentration (Tmax) of SPR719 | No participants were enrolled at study sites that were conducting intensive PK evaluations. | Posted | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
|
| |||||||||||||||||||||
| Primary | Area Under the Concentration-time Curve From Zero to Tau, Where Tau is the Dosing Interval (AUC0-tau) for SPR719 | No participants were enrolled at study sites that were conducting intensive PK evaluations. | Posted | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
|
| |||||||||||||||||||||
| Primary | Accumulation Ratio of SPR719 | No participants were enrolled at study sites that were conducting intensive PK evaluations. | Posted | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
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| |||||||||||||||||||||
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational/experimental) product, whether related to this product or not. This includes any newly occurring event or previous condition that has increased in severity or frequency since starting active or randomized treatment. The Investigator assessed the intensity for each AE reported during the study using the latest version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, as Mild, Moderate, Severe, Life-threatening, or Death. | All treated participants | Posted | Count of Participants | Participants | From first dose of study drug (Day 1) up to 28 days after last dose (56 days) |
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| Secondary | Number of Participants With Clinically Meaningful Change in Physical Examination Findings | Full physical examination were conducted on Day 1 and 28 days after last dose (Day 56) and included, at a minimum, assessment of the following systems: skin, head, ears, eyes, nose and throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system. Symptom-directed physical examinations were conducted at study visits on Days 7, 14, 21, and 28. | All treated participants | Posted | Count of Participants | Participants | Days 1, 7, 14, 21, 28, and 56 |
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| Secondary | Number of Participants Who Received Any Concomitant Medication During the Study | All treated participants | Posted | Count of Participants | Participants | Day 1 to Day 56 |
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| Secondary | Changes From Baseline in Laboratory Tests | Individual laboratory test results are not reported in order to protect patient confidentiality. | Posted | Days 1, 7, 14, 21, 28, and 56 |
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| Secondary | Number of Participants With Clinically Significant Out-of-normal Range Laboratory Tests | Clinical laboratory tests included serum chemistry, hematology, coagulation tests, and urinalysis. The investigator determined whether any changes in laboratory values were clinically significant based on the condition of the participant and the extent and duration of the deviation from the reference range. | All treated participants | Posted | Count of Participants | Participants | Days 1, 7, 14, 21, 28, and 56 |
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| Secondary | Shifts From Baseline in Selected Laboratory Tests Using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Shift Categories | No participants had out-of-range laboratory test results hence shift tables could not be created. | Posted | Days 1, 7, 14, 21, 28, and 56 |
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| Secondary | Changes From Baseline in Vital Sign Measurements | Vital signs measurements included systolic and diastolic blood pressure, pulse, temperature, and respiratory rate. | Individual vital sign measurement results are not reported in order to protect patient confidentiality. | Posted | Days 1, 7, 14, 21, 28, and 56 |
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| Secondary | Number of Participants With Clinically Significant Abnormal Electrocardiogram Findings | Standard 12-lead electrocardiogram (ECG) assessments included heart rate, cardiac rhythm, PR interval, RR interval, QRS interval, QT interval and QTC interval. Clinical significance was determined by the investigator. | All treated participants | Posted | Count of Participants | Participants | Days 1, 14, 28, and 56 |
|
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From first dose of study up to 28 days after last dose (56 days).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | SPR720 500 mg | SPR720 500 mg administered orally once daily for 28 days. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG001 | Placebo | Placebo administered orally once daily for 28 days. | 0 | 1 | 0 | 1 | 1 | 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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The PI may not publish the results prior to the first multi-site publication. If there is no multi-site publication within 18 months after Trial completion the PI may publish results from the trial, subject to the following. PI will submit proposed Publication to Sponsor 60 days prior to submission of the Publication. PI will, at Sponsor's request, delay such Publication for up to 90 days for Sponsor to obtain appropriate intellectual property protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jon Bruss | SperoTherapeutics | (+1) 269-352-3766 | jbruss@sperotherapeutics.com |
| Jan 24, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D015270 | Mycobacterium avium-intracellulare Infection |
| ID | Term |
|---|---|
| D009165 | Mycobacterium Infections, Nontuberculous |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Units | Counts |
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| Participants |
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