Mycobacterium Avium ComplexPhase 2NCT04553406
Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
A Phase 2 study testing SPR720 in people with Mycobacterium Avium Complex and Non-tuberculous Mycobacterium Pulmonary Disease, run by Spero Therapeutics at 9 sites in United States.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mycobacterium Avium Complex, Non-tuberculous Mycobacterium Pulmonary Disease
- What is being tested?
- SPR720
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 9 sitesUnited States
- Study dates
- 3 Dec 2020to 28 Jan 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 21Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Medical Facility
Altamonte Springs, Florida, 32701
Medical Facility
Atlantis, Florida, 33462
Medical Facility
Charlotte, North Carolina, 28207
Medical Facility
Clearwater, Florida, 33765
Medical Facility
Kissimmee, Florida, 34746
Medical Facility
Mooresville, North Carolina, 28117
Medical Facility
Pittsburgh, Pennsylvania, 15213
Medical Facility
West Palm Beach, Florida, 33407
Medical Facility
Winston-Salem, North Carolina, 27103
About this study
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
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)
- Being tested
- SPR720, Placebo, Open-label Standard of Care
- Medical subject headings
- Mycobacterium avium-intracellulare Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPR720Drug
Capsules for oral administration
PlaceboDrug
Capsules for oral administration
Open-label Standard of CareDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| SPR720 low dose | Experimental | SPR720 500 mg administered orally once daily for 28 days. Receives: Drug: SPR720 |
| SPR720 high dose | Experimental | SPR720 1000 mg administered orally once daily for 28 days. Receives: Drug: SPR720 |
| Placebo | Placebo comparator | Placebo administered orally once daily for 28 days Receives: Drug: Placebo |
| Standard of Care (SOC) | Active comparator | Standard of Care regimen per the Investigator's discretion. Receives: Drug: Open-label Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Accumulation Ratio of SPR719
Measured: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Secondary outcomes (8)
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.
Measured: 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.
Measured: Days 1, 7, 14, 21, 28, and 56
Number of Participants Who Received Any Concomitant Medication During the Study
Measured: Day 1 to Day 56
Changes From Baseline in Laboratory Tests
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: Days 1, 14, 28, and 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2020
- Study start3 Dec 2020
- Primary completion28 Jan 2021
- Study completion28 Jan 2021
Why it stopped: Business decision pending resolution of clinical hold with FDA
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mycobacterium Avium ComplexStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spero Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Melnick, MD, Study director, Spero Therapeutics Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04553406
- Sponsor's protocol ID
- SPR720-201
- Status last verified
- Nov 2021
- First submitted
- 1 Sep 2020
- Last updated
- 28 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04553406
- Acronym / sponsor ID
- SPR720-201
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business decision pending resolution of clinical hold with FDA
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Spero TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 3 Dec 2020 (actual)
- Primary completion
- 28 Jan 2021 (actual)
- Study completion
- 28 Jan 2021 (actual)
- First posted
- 17 Sep 2020 (actual)
- Results
- Posted 28 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SPR720 low dose | Experimental | Drug: SPR720SPR720 500 mg administered orally once daily for 28 days. |
| SPR720 high dose | Experimental | Drug: SPR720SPR720 1000 mg administered orally once daily for 28 days. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo administered orally once daily for 28 days |
| Standard of Care (SOC) | Active comparator | Drug: Open-label Standard of CareStandard of Care regimen per the Investigator's discretion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPR720Capsules for oral administration | Drug | SPR720 high dose, SPR720 low dose |
| PlaceboCapsules for oral administration | Drug | Placebo |
| Open-label Standard of CareStandard 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. | Drug | Standard of Care (SOC) |
Primary outcome
Maximum Plasma Concentration (Cmax) of SPR719
Time frame: 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
Time frame: 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
Time frame: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Accumulation Ratio of SPR719
Time frame: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
8 secondary outcomes
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: 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
Time frame: Days 1, 7, 14, 21, 28, and 56
Number of Participants Who Received Any Concomitant Medication During the Study
Time frame: Day 1 to Day 56
Changes From Baseline in Laboratory Tests
Time frame: Days 1, 7, 14, 21, 28, and 56
Number of Participants With Clinically Significant Out-of-normal Range Laboratory Tests
Time frame: 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
Time frame: Days 1, 7, 14, 21, 28, and 56
Changes From Baseline in Vital Sign Measurements
Time frame: Days 1, 7, 14, 21, 28, and 56
Number of Participants With Clinically Significant Abnormal Electrocardiogram Findings
Time frame: Days 1, 14, 28, and 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Melnick, MD study director
Spero Therapeutics Inc
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SPR720 in people with Mycobacterium Avium Complex and Non-tuberculous Mycobacterium Pulmonary Disease, run by Spero Therapeutics at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Plasma Concentration (Cmax) of SPR719 (time frame: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2022.