Phase 2a Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease

• ClinicalTrials.gov Identifier: NCT04553406
• Recruitment Status: Recruiting
• First Posted: September 17, 2020
• Last Update Posted: January 15, 2021
• Sponsor: Spero Therapeutics
• Information provided by (Responsible Party): Spero Therapeutics

Study Description

Brief Summary:

To evaluate the pharmacokinetics (PK) of SPR719 generated from the orally (po) administered SPR720 prodrug in a patient population with nontuberculous mycobacteria pulmonary disease (NTM-PD)

Condition or disease	Intervention/treatment	Phase
Mycobacterium Avium Complex	Drug: SPR720; Drug: Placebo; Drug: Open-label SOC	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Treatment Arms 1 to 3 are masked while Treatment Arm 4 is open-label
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 10, 2020
• Estimated Primary Completion Date: January 2022
• Estimated Study Completion Date: February 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: SPR720 low dose; SPR720 500 mg (2 capsules of 250 mg SPR720 and 2 capsules of placebo) administered orally once daily for 28 days	Drug: SPR720; 250 mg capsules
Experimental: SPR720 high dose; SPR720 1000 mg (4 capsules of 250 mg SPR720) administered orally once daily for 28 days	Drug: SPR720; 250 mg capsules
Placebo Comparator: Placebo; 4 capsules of placebo once daily for 28 days	Drug: Placebo; 4 capsules of matching placebo
Active Comparator: Standard of Care (SOC); Clarithromycin 500-1000 mg plus ethambutol HCl 15 mg/kg po once daily or Azithromycin 250-500 mg plus ethambutol HCl 15 mg/k po once daily. Optional rifampin 600 mg or rifabutin 300 mg po once daily may be added to the SOC regimen for up to 28 days. Additional SOC treatments may be considered in consultation with the medical monitor.	Drug: Open-label SOC; Clarithromycin 500-1000 mg plus ethambutol HCl 15 mg/kg po once daily or Azithromycin 250-500 mg plus ethambutol HCl 15 mg/k po once daily. Optional rifampin 600 mg or rifabutin 300 mg po once daily may be added to the SOC regimen for up to 28 days. Additional SOC treatments may be considered in consultation with the medical monitor.

Outcome Measures

Primary Outcome Measures :

1. Maximum plasma concentration (Cmax) [ Time Frame: From Day 1 to Day 28 ]
   For Treatment Arms 1, 2, and 3
2. Time to reach Cmax (Tmax) [ Time Frame: From Day 1 to Day 28 ]
   For Treatment Arms 1, 2, and 3
3. Area under the concentration-time curve from zero to tau, where tau is the dosing interval (AUC0-tau), [ Time Frame: From Day 1 to Day 28 ]
   For Treatment Arms 1, 2, and 3
4. Accumulation ratio of SPR719 [ Time Frame: From Day 1 to Day 28 ]
   For Treatment Arms 1, 2, and 3

Secondary Outcome Measures :

1. Reported adverse events (AEs) [ Time Frame: Day 1 to Day 56 ]
2. Clinically meaningful change in physical examination findings [ Time Frame: Day 1 to Day 56 ]
   To assess the incidents of abnormal body system assessments following 28 days of IP administration
3. Concomitant medication usage [ Time Frame: Day 1 to Day 56 ]
   The type and frequency of medications used
4. Changes from baseline in laboratory tests [ Time Frame: Day 1 to Day 56 ]
   To assess the incidents of abnormal hematology, biochemistry, coagulation and urinalysis assessments following 28 days of IP administration
5. Clinically significant (CS) out-of-normal range laboratory tests [ Time Frame: Day 1 to Day 56 ]
   To assess the incidents of clinically significant abnormal hematology, biochemistry, coagulation and urinalysis assessments following 28 days of IP administration
6. Shifts from baseline in selected laboratory tests using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 shift categories [ Time Frame: Day 1 to Day 56 ]
7. Changes from baseline in vital sign measurements [ Time Frame: Day 1 to Day 56 ]
   To assess the incidents of abnormal heart rate, blood pressure and body temperature assessments following 28 days of IP administration
8. 12-lead ECGs [ Time Frame: Day 1 to Day 56 ]
   To assess the incidents of abnormal heart rate, cardiac rhythm, PR interval, RR interval, QRS interval, QT interval and QTC interval assessments following 28 days of IP administration

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Caroline Wass; 8572421586; cwass@sperotherapeutics.com

Locations

United States, Florida

Medical Facility; Recruiting

Altamonte Springs, Florida, United States, 32701

Medical Facility; Recruiting

Atlantis, Florida, United States, 33462

Medical Facility; Recruiting

Clearwater, Florida, United States, 33765

Medical Facility; Recruiting

Kissimmee, Florida, United States, 34746

Medical Facility; Recruiting

West Palm Beach, Florida, United States, 33407

United States, North Carolina

Medical Facility; Recruiting

Charlotte, North Carolina, United States, 28207

Medical Facility; Recruiting

Mooresville, North Carolina, United States, 28117

Medical Facility; Recruiting

Winston-Salem, North Carolina, United States, 27103

United States, Pennsylvania

Medical Facility; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Spero Therapeutics

Investigators

• Study Director: David Melnick, MD; Spero Therapeutics, Inc.

More Information

• Responsible Party: Spero Therapeutics
• ClinicalTrials.gov Identifier: NCT04553406
• Other Study ID Numbers: SPR720-201
• First Posted: September 17, 2020
• Last Update Posted: January 15, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Mycobacterium Infections; Mycobacterium avium-intracellulare Infection; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Mycobacterium Infections, Nontuberculous