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

NCT04553406 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SPR720-201
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 9

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  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

  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

  Days 1, 7, 14, 21, 28, and 56

Study Arms (4)

SPR720 low dose

EXPERIMENTAL

SPR720 500 mg administered orally once daily for 28 days.

Drug: SPR720

SPR720 high dose

EXPERIMENTAL

SPR720 1000 mg administered orally once daily for 28 days.

Drug: SPR720

Placebo

PLACEBO COMPARATOR

Placebo administered orally once daily for 28 days

Drug: Placebo

Standard of Care (SOC)

ACTIVE COMPARATOR

Standard of Care regimen per the Investigator's discretion.

Drug: Open-label Standard of Care

Interventions

SPR720 DRUG

Capsules for oral administration

SPR720 high dose; SPR720 low dose

Placebo DRUG

Capsules for oral administration

Placebo

Open-label Standard of Care 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.

Standard of Care (SOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• chronic cough
• fatigue
• frequent throat clearing
• shortness of breath (dyspnea)
• coughing up of blood (hemoptysis)
• excessive mucus (sputum) production
• fever
• night sweats
• loss of appetite

You may not qualify if:

• 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%

Sponsors & Collaborators

• Spero Therapeutics: lead

Study Sites (9)

Medical Facility

Altamonte Springs, Florida, 32701, United States

Location

Medical Facility

Atlantis, Florida, 33462, United States

Location

Medical Facility

Clearwater, Florida, 33765, United States

Location

Medical Facility

Kissimmee, Florida, 34746, United States

Location

Medical Facility

West Palm Beach, Florida, 33407, United States

Location

Medical Facility

Charlotte, North Carolina, 28207, United States

Location

Medical Facility

Mooresville, North Carolina, 28117, United States

Location

Medical Facility

Winston-Salem, North Carolina, 27103, United States

Location

Medical Facility

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Mycobacterium avium-intracellulare Infection

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Dr. Jon Bruss
• Organization: SperoTherapeutics

jbruss@sperotherapeutics.com

(+1) 269-352-3766

Study Officials

• David Melnick, MD

  Spero Therapeutics Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Treatment Arms 1 to 3 are masked while Treatment Arm 4 is open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: September 17, 2020
• Study Start: December 3, 2020
• Primary Completion: January 28, 2021
• Study Completion: January 28, 2021
• Last Updated: February 28, 2022
• Results First Posted: February 28, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)