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

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)

Study Overview

• Status: Terminated
• Conditions: Mycobacterium Avium Complex; Non-tuberculous Mycobacterium Pulmonary Disease
• Intervention / Treatment: Drug: Placebo; Drug: SPR720; Drug: Open-label Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • 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
      • Medical Facility
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Medical Facility
    • Mooresville, North Carolina, United States, 28117
      • Medical Facility
    • Winston-Salem, North Carolina, United States, 27103
      • Medical Facility
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Medical Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Spero Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2020
• Primary Completion (Actual): January 28, 2021
• Study Completion (Actual): January 28, 2021

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2022
• Last Update Submitted That Met QC Criteria: February 3, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections, Nontuberculous; Lung Diseases; Mycobacterium Infections; Mycobacterium avium-intracellulare Infection
• Other Study ID Numbers: SPR720-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No