Back to resultsSafety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
Primary Purpose
Mycobacterium Avium Complex, Non-tuberculous Mycobacterium Pulmonary Disease
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
SPR720
Placebo
Open-label Standard of Care
Sponsored by
About this trial
This is an interventional treatment trial for Mycobacterium Avium Complex
Eligibility 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
Sites / Locations
- Medical Facility
- Medical Facility
- Medical Facility
- Medical Facility
- Medical Facility
- Medical Facility
- Medical Facility
- Medical Facility
- Medical Facility
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Active Comparator
Arm Label
SPR720 low dose
SPR720 high dose
Placebo
Standard of Care (SOC)
Arm Description
SPR720 500 mg administered orally once daily for 28 days.
SPR720 1000 mg administered orally once daily for 28 days.
Placebo administered orally once daily for 28 days
Standard of Care regimen per the Investigator's discretion.
Outcomes
Primary Outcome Measures
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.
Time to Reach Maximum Plasma Concentration (Tmax) of SPR719
Area Under the Concentration-time Curve From Zero to Tau, Where Tau is the Dosing Interval (AUC0-tau) for SPR719
Accumulation Ratio of SPR719
Secondary Outcome Measures
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.
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.
Number of Participants Who Received Any Concomitant Medication During the Study
Changes From Baseline in Laboratory Tests
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.
Shifts From Baseline in Selected Laboratory Tests Using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Shift Categories
Changes From Baseline in Vital Sign Measurements
Vital signs measurements included systolic and diastolic blood pressure, pulse, temperature, and respiratory rate.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04553406
Brief Title
Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
Official Title
A Randomized, Partially Blinded, Placebo- and Comparator-Controlled, Multicenter, Phase 2a, Dose Ranging, Proof-of-Concept Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of SPR720 as Compared With Placebo or Standard of Care for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Terminated
Why Stopped
Business decision pending resolution of clinical hold with FDA
Study Start Date
December 3, 2020 (Actual)
Primary Completion Date
January 28, 2021 (Actual)
Study Completion Date
January 28, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spero Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mycobacterium Avium Complex, Non-tuberculous Mycobacterium Pulmonary Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Treatment Arms 1 to 3 are masked while Treatment Arm 4 is open-label
Allocation
Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SPR720 low dose
Arm Type
Experimental
Arm Description
SPR720 500 mg administered orally once daily for 28 days.
Arm Title
SPR720 high dose
Arm Type
Experimental
Arm Description
SPR720 1000 mg administered orally once daily for 28 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered orally once daily for 28 days
Arm Title
Standard of Care (SOC)
Arm Type
Active Comparator
Arm Description
Standard of Care regimen per the Investigator's discretion.
Intervention Type
Drug
Intervention Name(s)
SPR720
Intervention Description
Capsules for oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Capsules for oral administration
Intervention Type
Drug
Intervention Name(s)
Open-label Standard of Care
Intervention Description
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.
Primary Outcome Measure Information:
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
Title
Time to Reach Maximum Plasma Concentration (Tmax) of SPR719
Time Frame
Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Title
Area Under the Concentration-time Curve From Zero to Tau, Where Tau is the Dosing Interval (AUC0-tau) for SPR719
Time Frame
Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Title
Accumulation Ratio of SPR719
Time Frame
Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Secondary Outcome Measure Information:
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)
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
Title
Number of Participants Who Received Any Concomitant Medication During the Study
Time Frame
Day 1 to Day 56
Title
Changes From Baseline in Laboratory Tests
Time Frame
Days 1, 7, 14, 21, 28, and 56
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
Title
Shifts From Baseline in Selected Laboratory Tests Using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Shift Categories
Time Frame
Days 1, 7, 14, 21, 28, and 56
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Melnick, MD
Organizational Affiliation
Spero Therapeutics Inc
Official's Role
Study Director
Facility Information:
Facility Name
Medical Facility
City
Altamonte Springs
State/Province
Florida
ZIP/Postal Code
32701
Country
United States
Facility Name
Medical Facility
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Medical Facility
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Facility Name
Medical Facility
City
Kissimmee
State/Province
Florida
ZIP/Postal Code
34746
Country
United States
Facility Name
Medical Facility
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Medical Facility
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Medical Facility
City
Mooresville
State/Province
North Carolina
ZIP/Postal Code
28117
Country
United States
Facility Name
Medical Facility
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Medical Facility
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
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