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

NCT ID: NCT04553406

Last Updated: 2022-02-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-03
• Study Completion Date: 2021-01-28

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)

Conditions

Mycobacterium Avium Complex; Non-tuberculous Mycobacterium Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

SPR720 low dose

SPR720 500 mg administered orally once daily for 28 days.

Group Type: EXPERIMENTAL

SPR720

Intervention Type: DRUG

Capsules for oral administration

SPR720 high dose

SPR720 1000 mg administered orally once daily for 28 days.

Group Type: EXPERIMENTAL

SPR720

Intervention Type: DRUG

Capsules for oral administration

Placebo

Placebo administered orally once daily for 28 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Capsules for oral administration

Standard of Care (SOC)

Standard of Care regimen per the Investigator's discretion.

Group Type: ACTIVE_COMPARATOR

Open-label Standard of Care

Intervention Type: DRUG

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.

Interventions

SPR720

Capsules for oral administration

Intervention Type: DRUG

Placebo

Capsules for oral administration

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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.

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%

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spero Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Melnick, MD

Role: STUDY_DIRECTOR

Spero Therapeutics Inc

Locations

Medical Facility

Altamonte Springs, Florida, United States

Medical Facility

Atlantis, Florida, United States

Medical Facility

Clearwater, Florida, United States

Medical Facility

Kissimmee, Florida, United States

Medical Facility

West Palm Beach, Florida, United States

Medical Facility

Charlotte, North Carolina, United States

Medical Facility

Mooresville, North Carolina, United States

Medical Facility

Winston-Salem, North Carolina, United States

Medical Facility

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

SPR720-201

Identifier Type: -

Identifier Source: org_study_id