Clinical trial NCT04553406: Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
Official title: A Randomized, Partially Blinded, Placebo- and Comparator-Controlled, Multicenter, Phase 2a, Dose Ranging, Proof-of-Concept Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of SPR720 as Compared With Placebo or Standard of Care for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Mycobacterium Avium Complex
Non-tuberculous Mycobacterium Pulmonary Disease
Lead sponsor: Spero Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-09-17
Enrollment: 2
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: 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)


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.
* Other inclusion criteria per protocol

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%
* Other exclusion criteria per protocol

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of SPR719
timeFrame: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
measure: Time to Reach Maximum Plasma Concentration (Tmax) of SPR719
timeFrame: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
measure: Area Under the Concentration-time Curve From Zero to Tau, Where Tau is the Dosing Interval (AUC0-tau) for SPR719
timeFrame: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
measure: Accumulation Ratio of SPR719
timeFrame: Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug (Day 1) up to 28 days after last dose (56 days)
measure: Number of Participants With Clinically Meaningful Change in Physical Examination Findings
timeFrame: Days 1, 7, 14, 21, 28, and 56
measure: Number of Participants Who Received Any Concomitant Medication During the Study
timeFrame: Day 1 to Day 56
measure: Changes From Baseline in Laboratory Tests
timeFrame: Days 1, 7, 14, 21, 28, and 56
measure: Number of Participants With Clinically Significant Out-of-normal Range Laboratory Tests
timeFrame: Days 1, 7, 14, 21, 28, and 56
measure: Shifts From Baseline in Selected Laboratory Tests Using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Shift Categories
timeFrame: Days 1, 7, 14, 21, 28, and 56
measure: Changes From Baseline in Vital Sign Measurements
timeFrame: Days 1, 7, 14, 21, 28, and 56
measure: Number of Participants With Clinically Significant Abnormal Electrocardiogram Findings
timeFrame: Days 1, 14, 28, and 56
Other outcomes:
Locations:
city: Altamonte Springs
country: United States
facility: Medical Facility
state: Florida
city: Atlantis
country: United States
facility: Medical Facility
state: Florida
city: Clearwater
country: United States
facility: Medical Facility
state: Florida
city: Kissimmee
country: United States
facility: Medical Facility
state: Florida
city: West Palm Beach
country: United States
facility: Medical Facility
state: Florida
city: Charlotte
country: United States
facility: Medical Facility
state: North Carolina
city: Mooresville
country: United States
facility: Medical Facility
state: North Carolina
city: Winston-Salem
country: United States
facility: Medical Facility
state: North Carolina
city: Pittsburgh
country: United States
facility: Medical Facility
state: Pennsylvania
Study officials:
affiliation: Spero Therapeutics Inc
name: David Melnick, MD
role: STUDY_DIRECTOR
References: