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Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04553406
Recruitment Status : Terminated (Business decision pending resolution of clinical hold with FDA)
First Posted : September 17, 2020
Results First Posted : February 28, 2022
Last Update Posted : February 28, 2022
Sponsor:
Information provided by (Responsible Party):
Spero Therapeutics

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
Mycobacterium Avium Complex Non-tuberculous Mycobacterium Pulmonary Disease Drug: SPR720 Drug: Placebo Drug: Open-label Standard of Care Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Treatment Arms 1 to 3 are masked while Treatment Arm 4 is open-label
Primary Purpose: Treatment
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
Actual Study Start Date : December 3, 2020
Actual Primary Completion Date : January 28, 2021
Actual Study Completion Date : January 28, 2021


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.





Primary Outcome Measures :
  1. 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.

  2. 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 ]
  3. 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 ]
  4. 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 Measures :
  1. 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) ]

    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.


  2. Number of Participants With Clinically Meaningful Change in Physical Examination Findings [ Time Frame: 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.

  3. Number of Participants Who Received Any Concomitant Medication During the Study [ Time Frame: Day 1 to Day 56 ]
  4. Changes From Baseline in Laboratory Tests [ Time Frame: Days 1, 7, 14, 21, 28, and 56 ]
  5. Number of Participants With Clinically Significant Out-of-normal Range Laboratory Tests [ Time Frame: 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.

  6. 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 ]
  7. Changes From Baseline in Vital Sign Measurements [ Time Frame: Days 1, 7, 14, 21, 28, and 56 ]
    Vital signs measurements included systolic and diastolic blood pressure, pulse, temperature, and respiratory rate.

  8. Number of Participants With Clinically Significant Abnormal Electrocardiogram Findings [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    1. chronic cough
    2. fatigue
    3. frequent throat clearing
    4. shortness of breath (dyspnea)
    5. coughing up of blood (hemoptysis)
    6. excessive mucus (sputum) production
    7. fever
    8. night sweats
    9. loss of appetite
    10. unintended weight loss
    11. wheezing
    12. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04553406


Locations
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United States, Florida
Medical Facility
Altamonte Springs, Florida, United States, 32701
Medical Facility
Atlantis, Florida, United States, 33462
Medical Facility
Clearwater, Florida, United States, 33765
Medical Facility
Kissimmee, Florida, United States, 34746
Medical Facility
West Palm Beach, Florida, United States, 33407
United States, North Carolina
Medical Facility
Charlotte, North Carolina, United States, 28207
Medical Facility
Mooresville, North Carolina, United States, 28117
Medical Facility
Winston-Salem, North Carolina, United States, 27103
United States, Pennsylvania
Medical Facility
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Spero Therapeutics
Investigators
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Study Director: David Melnick, MD Spero Therapeutics Inc
  Study Documents (Full-Text)

Documents provided by Spero Therapeutics:
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Responsible Party: Spero Therapeutics
ClinicalTrials.gov Identifier: NCT04553406    
Other Study ID Numbers: SPR720-201
First Posted: September 17, 2020    Key Record Dates
Results First Posted: February 28, 2022
Last Update Posted: February 28, 2022
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Lung Diseases
Respiratory Tract Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Mycobacterium Infections, Nontuberculous