Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
Study Details
Study Description
Brief Summary
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)
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: SPR720 low dose SPR720 500 mg administered orally once daily for 28 days. |
Drug: SPR720
Capsules for oral administration
|
Experimental: SPR720 high dose SPR720 1000 mg administered orally once daily for 28 days. |
Drug: SPR720
Capsules for oral administration
|
Placebo Comparator: Placebo Placebo administered orally once daily for 28 days |
Drug: Placebo
Capsules for oral administration
|
Active Comparator: Standard of Care (SOC) Standard of Care regimen per the Investigator's discretion. |
Drug: Open-label Standard of Care
Standard of Care regimen is at the Investigator's discretion; recommended 2-drug or 3-drug SOC, consisting of either:
Clarithromycin 500-1000 mg, plus ethambutol hydrochloride (HCl) 15 mg/kg orally once daily or
Azithromycin 250-500 mg plus ethambutol HCl 15 mg/kg orally once daily.
Optional rifampin 600 mg or rifabutin 300 mg orally once daily may be added to the SOC regimen for up to 28 days.
|
Outcome Measures
Primary Outcome Measures
- Maximum Plasma Concentration (Cmax) of SPR719 [Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose]
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.
- 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]
Secondary Outcome Measures
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) [From first dose of study drug (Day 1) up to 28 days after last dose (56 days)]
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.
- Number of Participants With Clinically Meaningful Change in Physical Examination Findings [Days 1, 7, 14, 21, 28, and 56]
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.
- 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 [Days 1, 7, 14, 21, 28, and 56]
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.
- 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 [Days 1, 7, 14, 21, 28, and 56]
Vital signs measurements included systolic and diastolic blood pressure, pulse, temperature, and respiratory rate.
- Number of Participants With Clinically Significant Abnormal Electrocardiogram Findings [Days 1, 14, 28, and 56]
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.
Eligibility Criteria
Criteria
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:
-
chronic cough
-
fatigue
-
frequent throat clearing
-
shortness of breath (dyspnea)
-
coughing up of blood (hemoptysis)
-
excessive mucus (sputum) production
-
fever
-
night sweats
-
loss of appetite
-
unintended weight loss
-
wheezing
-
chest pain
-
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:
-
Has disseminated or extrapulmonary NTM
-
Has end-stage NTM-PD or treatment-refractory NTM-PD and is unlikely to respond to protocol-specified SOC treatment
-
Had isolation on sputum cultures of any species of Mycobacterium other than a species included in MAC within the past 6 months
-
Had prior isolation of MAC with macrolide resistance
-
Has received any systemic (oral or IV) or inhaled antibiotic with activity against MAC between consent and randomization
-
Has a potentially confounding underlying pulmonary disease, including but not limited to cystic fibrosis, active pulmonary malignancy (primary or metastatic), NTM-hypersensitivity disease pneumoconiosis, or another advanced lung disease with a % predicted FEV1<30%
-
Other exclusion criteria per protocol
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Medical Facility | Altamonte Springs | Florida | United States | 32701 |
2 | Medical Facility | Atlantis | Florida | United States | 33462 |
3 | Medical Facility | Clearwater | Florida | United States | 33765 |
4 | Medical Facility | Kissimmee | Florida | United States | 34746 |
5 | Medical Facility | West Palm Beach | Florida | United States | 33407 |
6 | Medical Facility | Charlotte | North Carolina | United States | 28207 |
7 | Medical Facility | Mooresville | North Carolina | United States | 28117 |
8 | Medical Facility | Winston-Salem | North Carolina | United States | 27103 |
9 | Medical Facility | Pittsburgh | Pennsylvania | United States | 15213 |
Sponsors and Collaborators
- Spero Therapeutics
Investigators
- Study Director: David Melnick, MD, Spero Therapeutics Inc
Study Documents (Full-Text)
More Information
Publications
None provided.- SPR720-201
Study Results
Participant Flow
Recruitment Details | 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. |
---|---|
Pre-assignment Detail |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Period Title: Overall Study | ||
STARTED | 1 | 1 |
COMPLETED | 1 | 0 |
NOT COMPLETED | 0 | 1 |
Baseline Characteristics
Arm/Group Title | SPR720 500 mg | Placebo | Total |
---|---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. | Total of all reporting groups |
Overall Participants | 1 | 1 | 2 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
0
0%
|
1
100%
|
1
50%
|
>=65 years |
1
100%
|
0
0%
|
1
50%
|
Sex: Female, Male (Count of Participants) | |||
Female |
1
100%
|
1
100%
|
2
100%
|
Male |
0
0%
|
0
0%
|
0
0%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
0
0%
|
1
100%
|
1
50%
|
Not Hispanic or Latino |
1
100%
|
0
0%
|
1
50%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race/Ethnicity, Customized (Count of Participants) | |||
White |
1
100%
|
1
100%
|
2
100%
|
Region of Enrollment (participants) [Number] | |||
United States |
1
100%
|
1
100%
|
2
100%
|
Outcome Measures
Title | Maximum Plasma Concentration (Cmax) of SPR719 |
---|---|
Description | 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. |
Time Frame | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
No participants were enrolled at study sites that were conducting intensive PK evaluations. |
Arm/Group Title | SPR720 500 mg |
---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. |
Measure Participants | 0 |
Title | Time to Reach Maximum Plasma Concentration (Tmax) of SPR719 |
---|---|
Description | |
Time Frame | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
No participants were enrolled at study sites that were conducting intensive PK evaluations. |
Arm/Group Title | SPR720 500 mg |
---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. |
Measure Participants | 0 |
Title | Area Under the Concentration-time Curve From Zero to Tau, Where Tau is the Dosing Interval (AUC0-tau) for SPR719 |
---|---|
Description | |
Time Frame | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
No participants were enrolled at study sites that were conducting intensive PK evaluations. |
Arm/Group Title | SPR720 500 mg |
---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. |
Measure Participants | 0 |
Title | Accumulation Ratio of SPR719 |
---|---|
Description | |
Time Frame | Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
No participants were enrolled at study sites that were conducting intensive PK evaluations. |
Arm/Group Title | SPR720 500 mg |
---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. |
Measure Participants | 0 |
Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
---|---|
Description | 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. |
Time Frame | From first dose of study drug (Day 1) up to 28 days after last dose (56 days) |
Outcome Measure Data
Analysis Population Description |
---|
All treated participants |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Measure Participants | 1 | 1 |
All TEAEs |
1
100%
|
1
100%
|
Mild TEAEs |
1
100%
|
1
100%
|
Moderate TEAEs |
0
0%
|
0
0%
|
Severe TEAEs |
0
0%
|
0
0%
|
TEAEs leading to discontinuation of study drug |
0
0%
|
0
0%
|
TEAEs leading to discontinuation from study |
0
0%
|
0
0%
|
Title | Number of Participants With Clinically Meaningful Change in Physical Examination Findings |
---|---|
Description | 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. |
Time Frame | Days 1, 7, 14, 21, 28, and 56 |
Outcome Measure Data
Analysis Population Description |
---|
All treated participants |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Measure Participants | 1 | 1 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
Title | Number of Participants Who Received Any Concomitant Medication During the Study |
---|---|
Description | |
Time Frame | Day 1 to Day 56 |
Outcome Measure Data
Analysis Population Description |
---|
All treated participants |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Measure Participants | 1 | 1 |
Count of Participants [Participants] |
1
100%
|
1
100%
|
Title | Changes From Baseline in Laboratory Tests |
---|---|
Description | |
Time Frame | Days 1, 7, 14, 21, 28, and 56 |
Outcome Measure Data
Analysis Population Description |
---|
Individual laboratory test results are not reported in order to protect patient confidentiality. |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Measure Participants | 0 | 0 |
Title | Number of Participants With Clinically Significant Out-of-normal Range Laboratory Tests |
---|---|
Description | 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. |
Time Frame | Days 1, 7, 14, 21, 28, and 56 |
Outcome Measure Data
Analysis Population Description |
---|
All treated participants |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Measure Participants | 1 | 1 |
Clinical chemistry |
0
0%
|
0
0%
|
Hematology |
0
0%
|
0
0%
|
Coagulation tests |
0
0%
|
0
0%
|
Urinalysis |
0
0%
|
0
0%
|
Title | Shifts From Baseline in Selected Laboratory Tests Using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Shift Categories |
---|---|
Description | |
Time Frame | Days 1, 7, 14, 21, 28, and 56 |
Outcome Measure Data
Analysis Population Description |
---|
No participants had out-of-range laboratory test results hence shift tables could not be created. |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Measure Participants | 0 | 0 |
Title | Changes From Baseline in Vital Sign Measurements |
---|---|
Description | Vital signs measurements included systolic and diastolic blood pressure, pulse, temperature, and respiratory rate. |
Time Frame | Days 1, 7, 14, 21, 28, and 56 |
Outcome Measure Data
Analysis Population Description |
---|
Individual vital sign measurement results are not reported in order to protect patient confidentiality. |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Measure Participants | 0 | 0 |
Title | Number of Participants With Clinically Significant Abnormal Electrocardiogram Findings |
---|---|
Description | 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. |
Time Frame | Days 1, 14, 28, and 56 |
Outcome Measure Data
Analysis Population Description |
---|
All treated participants |
Arm/Group Title | SPR720 500 mg | Placebo |
---|---|---|
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. |
Measure Participants | 1 | 1 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
Adverse Events
Time Frame | From first dose of study up to 28 days after last dose (56 days). | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | SPR720 500 mg | Placebo | ||
Arm/Group Description | SPR720 500 mg administered orally once daily for 28 days. | Placebo administered orally once daily for 28 days. | ||
All Cause Mortality |
||||
SPR720 500 mg | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/1 (0%) | 0/1 (0%) | ||
Serious Adverse Events |
||||
SPR720 500 mg | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/1 (0%) | 0/1 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
SPR720 500 mg | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/1 (100%) | 1/1 (100%) | ||
Gastrointestinal disorders | ||||
Diarrhea | 1/1 (100%) | 0/1 (0%) | ||
Vomiting | 1/1 (100%) | 0/1 (0%) | ||
Nausea | 1/1 (100%) | 1/1 (100%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Dr. Jon Bruss |
---|---|
Organization | SperoTherapeutics |
Phone | (+1) 269-352-3766 |
jbruss@sperotherapeutics.com |
- SPR720-201