MAC PD Study

Mycobacterium avium complex (MAC) pulmonary disease (PD) is a rare condition that can have debilitating symptoms. Since MAC PD is fairly uncommon, there are limited therapies approved to treat it.

Because of this, scientists see a great need for more research to be done. Currently, they are researching drugs for individuals with MAC PD.

Patients meeting all of the following inclusion criteria should be considered for admission to the study:

1. Provided written informed consent.

2. Male or female, 18 years of age or older at the time of consent.

3. Has a prior diagnosis of NTM-PD due to MAC.

4. Has at least one prior positive culture (sputum or bronchoalveolar lavage) for MAC in the previous six months.

5. Has an induced sputum culture at screening positive for MAC by at least one of the following methods performed by the microbiological laboratory: quantitative culture on solid agar or growth on liquid media using Mycobacteria Growth Indicator Tubes (MGIT).

6. Is either treatment naive and has not received any prior treatment for MAC, OR if previously treated for MAC and meets all of the following criteria:

   1. Has a history of successful treatment with culture conversion.

   2. Has recent culture evidence of persistent, recurrent, or relapsed disease and

   3. Has been off therapy for at least three months.

7. In the opinion of the Investigator, is anticipated to initiate standard treatment (treatment naive) or reinitiate treatment (previously treated), but not within the next four months.

8. Has clinical signs and symptoms within the six weeks prior to 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

9. Has a measured forced expiratory volume in one second (% predicted forced expiratory volume in one second [FEV1]) greater or equal to 30% on pulmonary function test within three months prior to consent.

10. Has a chest radiograph (CXR) or computed tomography (CT) scan within three months prior to consent with findings consistent with NTM-PD. If no prior CXR or CT scan is available, a CXR or CT scan should be performed at screening to confirm eligibility.

11. If female, is of nonchildbearing potential (e.g., postmenopausal as demonstrated by follicle-stimulating hormone or surgical sterilization, i.e., tubal ligation or hysterectomy), or if of childbearing potential, is willing to commit to either sexual abstinence or use of at least two medically accepted, effective methods of birth control in combination (e.g., condom, spermicidal gel, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring) from consent through FU. If male, is willing not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, willing to use a condom in addition to having his female partner use a highly effective method of birth control (such as an intrauterine device, diaphragm, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation) from consent through FU.

12. Is willing and able to comply with all study assessments and adhere to the protocol schedule.

Patients meeting any of the following exclusion criteria will not be enrolled in the study:

1. In the opinion of the Investigator, is not a candidate for a four month delay in initiation of standard multidrug therapy in order to participate in a placebo-controlled clinical trial or observation (e.g., severe symptoms, extensive disease burden).

2. Has disseminated or extrapulmonary NTM.

3. Has end-stage NTM-PD or treatment-refractory NTM-PD.

4. Has isolation on sputum cultures of any species of Mycobacterium other than a species included in MAC within the past six months.

5. Has active tuberculosis at time of consent.

6. Has received any systemic (oral or IV) or inhaled antibiotic with activity against MAC between consent and Day 1.

7. 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 less than 30%.

8. Has a history of a positive test for HIV, known CD4 count less than 200nm3 within the last year before consent, or a diagnosis of AIDS.

9. Has an immunodeficiency or an immunocompromised condition, including neutropenia (less than 1000 neutrophils/mm3 obtained from the central laboratory at screening), hematologic malignancy, a history of hematopoietic stem cell transplant, a history of solid organ transplant, is receiving immunosuppressive therapy (e.g., cancer chemotherapy, monoclonal antibodies for autoimmune disease, or medications to prevent transplant rejection), and has had long-term use of systemic corticosteroids (e.g., greater or equal to 20 mg/day of prednisone or systemic equivalent for at least two weeks).

10. Has a history of known or suspected Clostridioides difficile infection.

11. Has a history of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures).

12. Has hepatic impairment at screening, as evidenced by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 x upper limit of normal (ULN) or total bilirubin greater than 1.5 x ULN, or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy).

13. Has renal impairment (creatinine clearance [CrCl] less than 50 mL/min) or end-stage renal disease requiring hemodialysis or peritoneal dialysis.

14. If female, is pregnant or breastfeeding.

15. Has a corrected QT (QTc) interval on electrocardiogram (ECG) greater than 470 ms.

16. Has consumed drugs or supplements that are strong cytochrome P450 (CYP)3A4 enzyme inducers or strong CYP3A4 inhibitors within four weeks of Day 1.

17. Has consumed drugs or supplements that are substrates of the hepatic transporters OATP1B1 or OATP1B3 within one week of Day 1.

18. Has received any investigational medication in the past three months before the time of consent.

19. Has any other condition or prior therapy, which, in the opinion of the Investigator, would make the patient unsuitable for this study, including compliance with all study assessments and adherence to the protocol schedule.

20. Prior exposure to SPR720.

Patients who are unable to comply with the requirements of the study or who in the opinion of the Investigator should not participate in the study are not eligible.

The study drug is called SPR720. It is a pill taken orally (by mouth).

If you have MAC PD and are eligible to enroll in this study, you will be assigned to a study treatment group to receive either SPR720 or a placebo. These will be in the form of pills taken orally (by mouth).

Most participants will be placed into a blinded study treatment group. If you are placed into this group, you will be randomly assigned to receive one of the following:

1. Placebo

2. SPR720 500 mg

3. SPR720 1000 mg

You will have about a 67% chance of receiving SPR720 and about a 33% chance of receiving placebo.

Blinded means that neither you nor the study staff will know which group you are in or whether you are receiving the study drug or the placebo.

Other participants will be placed into an open-label group. If you are placed into this group, you will receive the study drug and there will be no placebo.

Lab tests, physical exams, and other assessments and questionnaires will be conducted as part of this study.