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

Spero Therapeutics

Status and phase: Terminated; Phase 2

Conditions: Non-tuberculous Mycobacterium Pulmonary Disease; Mycobacterium Avium Complex

Treatments: Drug: SPR720; Drug: Open-label Standard of Care; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04553406

SPR720-201

Details and patient eligibility

About

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)

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

2 participants in 4 patient groups, including a placebo group

SPR720 low dose

Experimental group

Description:

SPR720 500 mg administered orally once daily for 28 days.

Treatment:

Drug: SPR720

SPR720 high dose

Experimental group

Description:

SPR720 1000 mg administered orally once daily for 28 days.

Treatment:

Drug: SPR720

Placebo

Placebo Comparator group

Description:

Placebo administered orally once daily for 28 days

Treatment:

Drug: Placebo

Standard of Care (SOC)

Active Comparator group

Description:

Standard of Care regimen per the Investigator's discretion.

Treatment:

Drug: Open-label Standard of Care