A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Participants With Mycobacterium Avium Complex (MAC) Pulmonary Disease

A Randomized, Double-Blinded, Placebo-Controlled, Multicenter, Phase 2, Dose-Ranging Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease

The purpose of the study is to evaluate

1. The microbiological response and clinical efficacy of SPR720 compared with placebo in participants with nontuberculous mycobacteria pulmonary disease (NTM-PD).
2. The safety and tolerability of SPR720 in a participants population with NTM- PD
3. The pharmacokinetic (PK) of SPR719, active moiety, following orally (po) administered prodrug SPR720 in a participant population with NTM-PD.

Study Overview

• Status: Recruiting
• Conditions: Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD)
• Intervention / Treatment: Drug: Placebo; Drug: SPR720 500 mg; Drug: SPR720 1000 mg

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Manoj Jivani; Phone Number: 8572421591; Email: MJivani@sperotherapeutics.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Medical Facility
  • California
    • Fresno, California, United States, 93701
      • Recruiting
      • Medical Facility
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Medical Facility
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Medical Facility
    • Northridge, California, United States, 91324
      • Recruiting
      • Medical Facility
    • Santa Clarita, California, United States, 91355
      • Recruiting
      • Medical Facility
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • Medical Facility
  • Florida
    • Kissimmee, Florida, United States, 34746-4654
      • Recruiting
      • Medical Facility
    • Loxahatchee Groves, Florida, United States, 33470
      • Recruiting
      • Medical Facility
    • Miami, Florida, United States, 33136
      • Recruiting
      • Medical Facility
    • Sebring, Florida, United States, 33870
      • Recruiting
      • Medical Facility
    • Tampa, Florida, United States, 33606
      • Recruiting
      • Medical Facility
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • Medical Facility
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • Recruiting
      • Medical Facility
  • Massachusetts
    • New Bedford, Massachusetts, United States, 02740
      • Recruiting
      • Medical Facility
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Medical Facility
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Medical Facility
  • New York
    • New Hyde Park, New York, United States, 11042
      • Recruiting
      • Medical Facility
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • Medical Facility
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Medical Facility
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Medical Facility
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Medical Facility
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Medical Facility
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical Facility
  • Texas
    • Denison, Texas, United States, 75020
      • Recruiting
      • Medical Facility
    • Sherman, Texas, United States, 75090
      • Recruiting
      • Medical Facility
    • Tyler, Texas, United States, 75708
      • Recruiting
      • Medical Facility

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Has a prior diagnosis of NTM-PD due to MAC according to American Thoracic Society (ATS) criteria
2. Has at least one prior lower respiratory culture (sputum or bronchoalveolar lavage [BAL]) positive for MAC in the 12 months prior to consent
3. Has an induced sputum culture at Screening positive for MAC by quantitative culture on solid agar

4. Is either treatment naïve and has not received any prior treatment for MAC, OR if previously treated for MAC and meets all of the following criteria:

   1. Has a history of successful treatment with sputum culture conversion to negative
   2. Has recent sputum or BAL culture evidence of recurrent or relapsed disease and
   3. Has been off therapy for at least 3 months prior to consent

5. Has clinical signs and symptoms within the 6 weeks prior to consent that are consistent with NTM-PD ≥2 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 (temperature >38ºC or >100.4ºF)
   8. night sweats
   9. loss of appetite
   10. unintended weight loss
   11. wheezing
   12. chest pain
6. Has a measured forced expiratory volume in the first second following maximal inhalation (FEV1) % predicted ≥30% within 3 months prior to consent. If prior FEV1% predicted test result is not available, obtain FEV1% predicted at Screening to confirm eligibility

Exclusion Criteria:

1. In the opinion of the Investigator, is not a candidate for a 5-month delay in initiation of standard multidrug therapy to participate in a placebo-controlled clinical trial (e.g., participant has severe symptoms or, extensive disease burden)
2. Has disseminated or extrapulmonary NTM disease
3. Has end-stage NTM-PD or treatment-refractory NTM-PD
4. Has isolation on lower respiratory (sputum or BAL) cultures of any Mycobacterium species other than those included in MAC within the 6 months prior to consent
5. Has any other condition or prior therapy, which, in the opinion of the Investigator, would make the participant unsuitable for this study, including compliance with all study assessments and adherence to the protocol schedule of assessment

6. Prior exposure to SPR720. Participants who are unable to comply with the requirements of the study or who in the opinion of the Investigator should not participate in the study are not eligible

   • Other inclusion and exclusion criteria as per protocol may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Double Blind: Placebo; Participants will receive matching placebo 4 capsules, orally once daily (QD) for 56 days.	Drug: Placebo; Placebo-matching capsules will be administered orally.
Experimental: Double Blind: SPR720 500 mg; Participants will receive SPR720 500 milligrams (mg) [250 mg × 2 capsules and 2 matching placebo capsules, orally QD for 56 days.	Drug: SPR720 500 mg; SPR720 500 mg (250 mg × 2 capsules) will be administered orally.
Experimental: Double Blind: SPR720 1000 mg; Participants will receive SPR720 1000 mg [250 mg × 4 capsules], orally QD for 56 days.	Drug: SPR720 1000 mg; SPR720 500 mg (250 mg × 4 capsules) will be administered orally.
Experimental: Open-label: SPR720 1000 mg; Participants will receive SPR720 1000 mg [250 mg × 4 capsules], orally QD for 56 days.	Drug: SPR720 1000 mg; SPR720 500 mg (250 mg × 4 capsules) will be administered orally.
Experimental: Open Label: SPR720 500 mg; Participants will receive SPR720 500 mg [250 mg × 2 capsules], orally twice daily (BID) for 56 days.	Drug: SPR720 500 mg; SPR720 500 mg (250 mg × 2 capsules) will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Slope of the Weekly Sputum Log10 Colony Forming Units Per Millilitre (CFU/mL) Change From Day 1 Through 56 in micro-Intent to Treat (m-ITT) Population	Days 1 through 56 (end of the treatment [EOT])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slope of the Weekly Sputum Log10 CFU/mL Change From Days 1 Through 28 in micro-ITT Population		Days 1 through 28
Slope of the Time to Positivity (TTP) using MGIT on Samples of Induced Sputum From Days 1 Through 56 (EOT) in micro-ITT Population		Days 1 through 56 (EOT)
Change from Baseline in the Sputum Log10 CFU/mL in the micro-ITT Population		Days 1 through 56 (EOT)
Change from Baseline in the Sputum TTP Using MGIT in micro-ITT Population		Days 1 through 56 (EOT)
Time to Negative Sputum Culture in micro-ITT Population		Days 1 through 56 (EOT)
Percent with Negative Sputum Culture in micro-ITT Population		Days 14 through Day 84 (FU)
Changes in Susceptibility in SPR719 From Days 1 through 56 (EOT) in the micro-ITT Population	Susceptibility is ≥4-fold increase in minimum inhibitory concentration for same pathogen identified at Baseline.	Days 1 through 56 (EOT)
Clinical Response in the micro-ITT Population	Investigator indicated their assessment of participants overall clinical response as resolved, improved, unchanged, or worsened.	Baseline up to Day 84 (FU)
Clinical Response in the Clinically Evaluable (CE) Populations	Investigator indicated their assessment of participants overall clinical response as resolved, improved, unchanged, or worsened.	Baseline up to Day 84 (FU)
Change From Baseline in 11-point Nontuberculous Mycobacteria Pulmonary Disease (NTM-PD) Symptoms and Impact Scale for Quality of Life (QOL) Assessments	The 11-point NTM-PD Symptoms and Impact Scale will evaluate specific clinical signs and symptoms and QOL improvements and will include symptoms of chronic cough, fatigue, frequent throat clearing, dyspnea, hemoptysis, excessive mucus (sputum) production, chills, night sweats, loss of appetite, unintended weight loss, wheezing, and chest pain.	Baseline up to FU Day 84
Change From Baseline in 6-point Patient Global Impression of Severity (PGI-S) Scale for Quality of Life (QOL) Assessments	The PGI-S scale is comprised of a 6-point verbal descriptor scale to determine meaningful change reported for the other symptom ratings in participants with NTM-PD.	Baseline up to FU Day 84
Change From Baseline in 7-point Patient Global Impression of Change (PGI-C) scale for Quality of Life (QOL) Assessments	The PGI-C scale is a patient-reported rating of improvement on a 7-point verbal descriptor scale.	Baseline up to FU Day 84
Change From Baseline in Flu, COVID-19, or Other Illness Questionnaire (2 questions) for Quality of Life (QOL) Assessments	This 2-question form will assess the participants flu, COVID-19 or other illness status and how these illnesses have affected the participants NTM-PD disease over the past 7 days.	Baseline up to FU Day 84
Change from Baseline in PROMIS® V1.0 Fatique Shortform 7a scale for Quality of Life (QOL) Assessments	The PROMIS® scale will assess the participants experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities using a validated 5-point Likert scale.	Baseline up to FU Day 84
Number of Participants with Treatment Emergent Adverse Events (TEAEs)	An adverse event is any untoward medical occurrence in a participant or clinical investigation participant 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.	From first dose of study drug (Day 1) up to follow up Day 84
Maximum Plasma Concentration (Cmax) (Intensive PK group only)		Pre-dose and post-dose on Days 1 and 14
Time to reach Cmax (Tmax) (Intensive PK group only)		Pre-dose and post-dose on Days 1 and 14
Area Under the Concentration-time Curve (AUC0-τ) (Intensive PK group only)		Pre-dose and post-dose on Days 1 and 14
Accumulation Ratio of SPR719 Cmax on Day 14 Compared to Day 1 (Intensive PK group only)		Pre-dose and post-dose on Days 1 and 14
Accumulation Ratio of SPR719 AUC0-τ on Day 14 Compared to Day 1 (Intensive PK group only)		Pre-dose and post-dose on Days 1 and 14

Collaborators and Investigators

• Sponsor: Spero Therapeutics
• Investigators: Study Director: Kamal Hamed, MD, Spero Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 11, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: MAC; Pulmonary disease; Mycobacterium avium Complex
• 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: SPR720-202

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
• product manufactured in and exported from the U.S.: No