Clinical trial NCT05496374: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD)
Keywords: Mycobacterium avium Complex
MAC
Pulmonary disease
Lead sponsor: Spero Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-08-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Days 1 through 56 (end of the treatment [EOT])
Secondary outcomes:
measure: Slope of the Weekly Sputum Log10 CFU/mL Change From Days 1 Through 28 in micro-ITT Population
timeFrame: Days 1 through 28
measure: Slope of the Time to Positivity (TTP) using MGIT on Samples of Induced Sputum From Days 1 Through 56 (EOT) in micro-ITT Population
timeFrame: Days 1 through 56 (EOT)
measure: Change from Baseline in the Sputum Log10 CFU/mL in the micro-ITT Population
timeFrame: Days 1 through 56 (EOT)
measure: Change from Baseline in the Sputum TTP Using MGIT in micro-ITT Population
timeFrame: Days 1 through 56 (EOT)
measure: Time to Negative Sputum Culture in micro-ITT Population
timeFrame: Days 1 through 56 (EOT)
measure: Percent with Negative Sputum Culture in micro-ITT Population
timeFrame: Days 14 through Day 84 (FU)
measure: Changes in Susceptibility in SPR719 From Days 1 through 56 (EOT) in the micro-ITT Population
timeFrame: Days 1 through 56 (EOT)
measure: Clinical Response in the micro-ITT Population
timeFrame: Baseline up to Day 84 (FU)
measure: Clinical Response in the Clinically Evaluable (CE) Populations
timeFrame: Baseline up to Day 84 (FU)
measure: Change From Baseline in 11-point Nontuberculous Mycobacteria Pulmonary Disease (NTM-PD) Symptoms and Impact Scale for Quality of Life (QOL) Assessments
timeFrame: Baseline up to FU Day 84
measure: Change From Baseline in 6-point Patient Global Impression of Severity (PGI-S) Scale for Quality of Life (QOL) Assessments
timeFrame: Baseline up to FU Day 84
measure: Change From Baseline in 7-point Patient Global Impression of Change (PGI-C) scale for Quality of Life (QOL) Assessments
timeFrame: Baseline up to FU Day 84
measure: Change From Baseline in Flu, COVID-19, or Other Illness Questionnaire (2 questions) for Quality of Life (QOL) Assessments
timeFrame: Baseline up to FU Day 84
measure: Change from Baseline in PROMIS® V1.0 Fatique Shortform 7a scale for Quality of Life (QOL) Assessments
timeFrame: Baseline up to FU Day 84
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug (Day 1) up to follow up Day 84
measure: Maximum Plasma Concentration (Cmax) (Intensive PK group only)
timeFrame: Pre-dose and post-dose on Days 1 and 14
measure: Time to reach Cmax (Tmax) (Intensive PK group only)
timeFrame: Pre-dose and post-dose on Days 1 and 14
measure: Area Under the Concentration-time Curve (AUC0-τ) (Intensive PK group only)
timeFrame: Pre-dose and post-dose on Days 1 and 14
measure: Accumulation Ratio of SPR719 Cmax on Day 14 Compared to Day 1 (Intensive PK group only)
timeFrame: Pre-dose and post-dose on Days 1 and 14
measure: Accumulation Ratio of SPR719 AUC0-τ on Day 14 Compared to Day 1 (Intensive PK group only)
timeFrame: Pre-dose and post-dose on Days 1 and 14
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Medical Facility
state: Alabama
city: Fresno
country: United States
facility: Medical Facility
state: California
city: Los Angeles
country: United States
facility: Medical Facility
state: California
city: Newport Beach
country: United States
facility: Medical Facility
state: California
city: Northridge
country: United States
facility: Medical Facility
state: California
city: Santa Clarita
country: United States
facility: Medical Facility
state: California
city: Washington
country: United States
facility: Medical Facility
state: District of Columbia
city: Kissimmee
country: United States
facility: Medical Facility
state: Florida
city: Loxahatchee Groves
country: United States
facility: Medical Facility
state: Florida
city: Miami
country: United States
facility: Medical Facility
state: Florida
city: Sebring
country: United States
facility: Medical Facility
state: Florida
city: Tampa
country: United States
facility: Medical Facility
state: Florida
city: Atlanta
country: United States
facility: Medical facility
state: Georgia
city: Iowa City
country: United States
facility: Medical Facility
state: Iowa
city: Kansas City
country: United States
facility: Medical Facility
state: Kansas
city: New Bedford
country: United States
facility: Medical Facility
state: Massachusetts
city: Rochester
country: United States
facility: Medical Facility
state: Minnesota
city: Lebanon
country: United States
facility: Medical Facility
state: New Hampshire
city: New Hyde Park
country: United States
facility: Medical Facility
state: New York
city: Chapel Hill
country: United States
facility: Medical Facility
state: North Carolina
city: Winston-Salem
country: United States
facility: Medical Facility
state: North Carolina
city: Cleveland
country: United States
facility: Medical Facility
state: Ohio
city: Portland
country: United States
facility: Medical Facility
state: Oregon
city: Pittsburgh
country: United States
facility: Medical Facility
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Facility
state: South Carolina
city: Denison
country: United States
facility: Medical Facility
state: Texas
city: Sherman
country: United States
facility: Medical Facility
state: Texas
city: Tyler
country: United States
facility: Medical Facility
state: Texas
Study officials:
affiliation: Spero Therapeutics Inc
name: Kamal Hamed, MD
role: STUDY_DIRECTOR
References: