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

• ClinicalTrials.gov Identifier: NCT05496374
• Recruitment Status: Recruiting
• First Posted: August 11, 2022
• Last Update Posted: April 12, 2024
• Sponsor: Spero Therapeutics
• Information provided by (Responsible Party): Spero Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD)	Drug: Placebo; Drug: SPR720 500 mg; Drug: SPR720 1000 mg	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 14, 2022
• Estimated Primary Completion Date: October 2024
• Estimated Study Completion Date: October 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Days 1 through 56 (end of the treatment [EOT]) ]

Secondary Outcome Measures :

1. Slope of the Weekly Sputum Log10 CFU/mL Change From Days 1 Through 28 in micro-ITT Population [ Time Frame: Days 1 through 28 ]
2. Slope of the Time to Positivity (TTP) using MGIT on Samples of Induced Sputum From Days 1 Through 56 (EOT) in micro-ITT Population [ Time Frame: Days 1 through 56 (EOT) ]
3. Change from Baseline in the Sputum Log10 CFU/mL in the micro-ITT Population [ Time Frame: Days 1 through 56 (EOT) ]
4. Change from Baseline in the Sputum TTP Using MGIT in micro-ITT Population [ Time Frame: Days 1 through 56 (EOT) ]
5. Time to Negative Sputum Culture in micro-ITT Population [ Time Frame: Days 1 through 56 (EOT) ]
6. Percent with Negative Sputum Culture in micro-ITT Population [ Time Frame: Days 14 through Day 84 (FU) ]
7. Changes in Susceptibility in SPR719 From Days 1 through 56 (EOT) in the micro-ITT Population [ Time Frame: Days 1 through 56 (EOT) ]
   Susceptibility is ≥4-fold increase in minimum inhibitory concentration for same pathogen identified at Baseline.
8. Clinical Response in the micro-ITT Population [ Time Frame: Baseline up to Day 84 (FU) ]
   Investigator indicated their assessment of participants overall clinical response as resolved, improved, unchanged, or worsened.
9. Clinical Response in the Clinically Evaluable (CE) Populations [ Time Frame: Baseline up to Day 84 (FU) ]
   Investigator indicated their assessment of participants overall clinical response as resolved, improved, unchanged, or worsened.
10. Change From Baseline in 11-point Nontuberculous Mycobacteria Pulmonary Disease (NTM-PD) Symptoms and Impact Scale for Quality of Life (QOL) Assessments [ Time Frame: Baseline up to FU Day 84 ]
    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.
11. Change From Baseline in 6-point Patient Global Impression of Severity (PGI-S) Scale for Quality of Life (QOL) Assessments [ Time Frame: Baseline up to FU Day 84 ]
    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.
12. Change From Baseline in 7-point Patient Global Impression of Change (PGI-C) scale for Quality of Life (QOL) Assessments [ Time Frame: Baseline up to FU Day 84 ]
    The PGI-C scale is a patient-reported rating of improvement on a 7-point verbal descriptor scale.
13. Change From Baseline in Flu, COVID-19, or Other Illness Questionnaire (2 questions) for Quality of Life (QOL) Assessments [ Time Frame: Baseline up to FU Day 84 ]
    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.
14. Change from Baseline in PROMIS® V1.0 Fatique Shortform 7a scale for Quality of Life (QOL) Assessments [ Time Frame: Baseline up to FU Day 84 ]
    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.
15. Number of Participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug (Day 1) up to follow up Day 84 ]
    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.
16. Maximum Plasma Concentration (Cmax) (Intensive PK group only) [ Time Frame: Pre-dose and post-dose on Days 1 and 14 ]
17. Time to reach Cmax (Tmax) (Intensive PK group only) [ Time Frame: Pre-dose and post-dose on Days 1 and 14 ]
18. Area Under the Concentration-time Curve (AUC0-τ) (Intensive PK group only) [ Time Frame: Pre-dose and post-dose on Days 1 and 14 ]
19. Accumulation Ratio of SPR719 Cmax on Day 14 Compared to Day 1 (Intensive PK group only) [ Time Frame: Pre-dose and post-dose on Days 1 and 14 ]
20. Accumulation Ratio of SPR719 AUC0-τ on Day 14 Compared to Day 1 (Intensive PK group only) [ Time Frame: Pre-dose and post-dose on Days 1 and 14 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Manoj Jivani; 8572421591; MJivani@sperotherapeutics.com

Locations

United States, Alabama

Medical Facility; Recruiting

Birmingham, Alabama, United States, 35233

United States, California

Medical Facility; Recruiting

Fresno, California, United States, 93701

Medical Facility; Recruiting

Los Angeles, California, United States, 90033

Medical Facility; Recruiting

Newport Beach, California, United States, 92663

Medical Facility; Recruiting

Northridge, California, United States, 91324

Medical Facility; Recruiting

Santa Clarita, California, United States, 91355

United States, District of Columbia

Medical Facility; Recruiting

Washington, District of Columbia, United States, 20007

United States, Florida

Medical Facility; Recruiting

Kissimmee, Florida, United States, 34746-4654

Medical Facility; Recruiting

Loxahatchee Groves, Florida, United States, 33470

Medical Facility; Recruiting

Miami, Florida, United States, 33136

Medical Facility; Recruiting

Sebring, Florida, United States, 33870

Medical Facility; Recruiting

Tampa, Florida, United States, 33606

United States, Iowa

Medical Facility; Recruiting

Iowa City, Iowa, United States, 52242

United States, Kansas

Medical Facility; Recruiting

Kansas City, Kansas, United States, 66103

United States, Massachusetts

Medical Facility; Recruiting

New Bedford, Massachusetts, United States, 02740

United States, Minnesota

Medical Facility; Recruiting

Rochester, Minnesota, United States, 55905

United States, New Hampshire

Medical Facility; Recruiting

Lebanon, New Hampshire, United States, 03756

United States, New York

Medical Facility; Recruiting

New Hyde Park, New York, United States, 11042

United States, North Carolina

Medical Facility; Recruiting

Chapel Hill, North Carolina, United States, 27599

Medical Facility; Recruiting

Winston-Salem, North Carolina, United States, 27103

United States, Ohio

Medical Facility; Recruiting

Cleveland, Ohio, United States, 44106

United States, Oregon

Medical Facility; Recruiting

Portland, Oregon, United States, 97239

United States, Pennsylvania

Medical Facility; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

United States, South Carolina

Medical Facility; Recruiting

Charleston, South Carolina, United States, 29425

United States, Texas

Medical Facility; Recruiting

Denison, Texas, United States, 75020

Medical Facility; Recruiting

Sherman, Texas, United States, 75090

Medical Facility; Recruiting

Tyler, Texas, United States, 75708

Sponsors and Collaborators

Spero Therapeutics

Investigators

• Study Director: Kamal Hamed, MD; Spero Therapeutics Inc

More Information

• Responsible Party: Spero Therapeutics
• ClinicalTrials.gov Identifier: NCT05496374
• Other Study ID Numbers: SPR720-202
• First Posted: August 11, 2022
• Last Update Posted: April 12, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Spero Therapeutics:

Mycobacterium avium Complex; MAC; Pulmonary disease

Additional relevant MeSH terms:

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