Oral Omadacycline vs. Placebo in Adults With NTM Pulmonary Disease Caused by Mycobacterium Abscessus Complex (MABc)

Sponsor

Paratek Pharmaceuticals Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04922554

Collaborator

(none)

Enrollment

Locations

Arms

23.5

Anticipated Duration (Months)

4.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and tolerability of oral omadacycline as compared to placebo in the treatment of adults with Nontuberculous Mycobacterial (NTM) pulmonary disease caused by Mycobacterium abscessus complex (MABc)

Condition or Disease	Intervention/Treatment	Phase
Mycobacterium Infections, Nontuberculous Mycobacterium Abscessus Infection Nontuberculous Mycobacterial Lung Disease Nontuberculous Mycobacterial Pulmonary Infection	Drug: Omadacycline Oral Tablet Drug: Placebo	Phase 2

Detailed Description

The total duration of subject participation in the study is approximately 5 months which includes a total duration of study treatment for approximately 3 months (84 days). Eligible participants will be randomized 1.5:1 to receive 3 months of treatment with either omadacycline or placebo (monotherapy). The study will use a double-dummy design in order to maintain the study blinding.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Ph. 2, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy, Safety, & Tolerability of Oral Omadacycline in Adults With NTM Pulmonary Disease Caused by Mycobacterium Abscessus Complex

Actual Study Start Date :

Oct 15, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omadacycline 300 mg PO omadacycline 150 mg tablets (x 2) administered orally, once daily, q24h	Drug: Omadacycline Oral Tablet omadacycline 300 mg orally, once daily (150 mg tablets x 2) Other Names: Nuzyra
Placebo Comparator: Placebo PO Placebo tablets resembling omadacycline (x 2) administered once daily, q24h	Drug: Placebo placebo tablets resembling omadacycline orally, once daily (x 2 tablets) Other Names: placebo tablets

Arm

Intervention/Treatment

Experimental: Omadacycline 300 mg PO

omadacycline 150 mg tablets (x 2) administered orally, once daily, q24h

Drug: Omadacycline Oral Tablet

omadacycline 300 mg orally, once daily (150 mg tablets x 2)

Other Names:

Nuzyra

Placebo Comparator: Placebo PO

Placebo tablets resembling omadacycline (x 2) administered once daily, q24h

Drug: Placebo

placebo tablets resembling omadacycline orally, once daily (x 2 tablets)

Other Names:

placebo tablets

Outcome Measures

Primary Outcome Measures

Clinical Response on NTM Symptom Assessment Scale at Day 84 [Day 1 to Day 84/EOT]
Improvement in severity of at least 50% of symptoms present at baseline
Reported adverse events (AEs) [Day 1 to Day 84/EOT]
To assess reported adverse events
Changes from baseline in laboratory tests [Day 1 to Day 84/EOT]
To assess the incidents of abnormal hematology, biochemistry, coagulation and urinalysis assessments following 84 days of IP administration
Clinically significant (CS), outside normal range laboratory tests [Day 1 to Day 84/EOT]
To assess the incidents of CS abnormal hematology, biochemistry, coagulation and urinalysis assessments following 84 days of IP administration
Changes from baseline in vital signs [Day 1 to Day 84/EOT]
To assess the incidents of abnormal heart rate and blood pressure assessments following 84 days of IP administration
Clinically significant (CS) vital signs [Day 1 to Day 84/EOT]
To assess the incidents of CS heart rate and blood pressure following 84 days of IP administration
Changes from baseline in electrocardiogram (ECG) [Day 1 to Day 84/EOT]
To assess the incidents of abnormal heart rate, cardiac rhythm, PR interval, RR interval, QRS interval, QT interval and QTc interval assessments following 84 days of IP administration
Clinically significant (CS) electrocardiogram (ECG) findings [Day 1 to Day 84/EOT]
To assess the incidents of CS and QTc interval assessments following 84 days of IP administration

Secondary Outcome Measures

Change from baseline in the total score of the Quality of Life - Bronchiectasis (QOL-B) questionnaire [Day 1 to Day 84/EOT]
Change from baseline in global score and individual domain scores of the St. George Respiratory Questionnaire (SGRQ) [Day 1 to Day 84/EOT]
Change from baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) [Day 1 to Day 84/EOT]
Change from baseline in Patient Clinical Impression of Severity (PGI-S) [Day 1 to Day 84/EOT]
Change from baseline in Patient Clinical Impression of Change (PGI-C) [Day 1 to Day 84/EOT]
Change from baseline in Clinical Global Impression - Severity of Illness (CGI-S) [Day 1 to Day 84/EOT]
Change from baseline in Clinical Global Impression - Improvement (CGI-I) [Day 1 to Day 84/EOT]
Patients reporting no new symptoms with a severity worse than mild on the NTM Symptom Assessment Questionnaire [Day 1 to Day 84/EOT]
Decrease in quantitative sputum culture at Day 84 [Day 1 to Day 84/EOT]
Time to growth in liquid medium only [Day 1 to Day 84/EOT]
Time to first negative sputum culture [Day 1 to Day 84/EOT]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Has a diagnosis of Nontuberculous Mycobacterial pulmonary disease caused by MABc
Has at least 2 of the following NTM-infection symptoms present at Screening and Baseline: chronic cough, coughing up blood (hemoptysis), wheezing, chest pain, frequent throat clearing, phlegm or sputum production, shortness of breath, fatigue, fever, night sweats, poor appetite, and/or weight loss.
At least 1 positive pulmonary (sputum) culture for MABc in the 6 months prior to Screening and 1 positive culture at Screening
Radiographic evidence of MABc infection via computed tomography (CT) scan of the chest within 3 months prior to Screening
In the opinion of the investigator, guideline-directed antibiotic therapy for treatment of MABc will not be required within the next 3 months, and a delay, in order for the subject to participate in a placebo-controlled clinical trial, is considered reasonable and clinically acceptable
Additional inclusion criteria as per protocol

Key Exclusion Criteria:

Has received antibiotic treatment within 6 months prior to Screening for MABc or MAC
Has received systemic or inhaled antibiotic therapy (other than chronic macrolide therapy) within 4 weeks prior to Screening
Has any of the following medical conditions:
Active pulmonary malignancy, or any type of malignancy requiring chemotherapy or radiation within 1 year prior to Screening
Active allergic bronchopulmonary mycosis, or any other condition requiring chronic treatment with systemic corticosteroids within 90 days prior to Screening
Radiologic evidence of cavitary disease
Known active pulmonary tuberculosis
Cystic fibrosis
History of lung transplantation
Another advanced lung disease with a known percent predicted forced expiratory volume in 1 second < 30%.
Disseminated or extra-pulmonary NTM disease
Has been previously treated with omadacycline
Has a history of hypersensitivity or allergic reaction to tetracyclines
Additional exclusion criteria as per protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Cystic Fibrosis Research Center	Birmingham	Alabama	United States	35294
2	Stanford University	Stanford	California	United States	94305
3	Georgetown University Hospital	Washington	District of Columbia	United States	20057
4	Central Florida Pulmonary Group	Altamonte Springs	Florida	United States	32701
5	St. Francis Medical Institute	Clearwater	Florida	United States	33765
6	University of Florida-College of Medicine- Jacksonville	Jacksonville	Florida	United States	32209
7	University of South Florida	Tampa	Florida	United States	33612
8	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
9	Johns Hopkins University	Baltimore	Maryland	United States	21287
10	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
11	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
12	Pulmonary Health Physicians, PC	Liverpool	New York	United States	13088
13	Southeastern Research Center	Winston-Salem	North Carolina	United States	27103
14	Oregon Health & Science University	Portland	Oregon	United States	97239
15	Medical University of South Carolina (MUSC)	Charleston	South Carolina	United States	29425
16	Baylor University Medical Center / Baylor Scott and White Research Institute	Dallas	Texas	United States	75201
17	The University of Texas Health Science Center at Tyler	Tyler	Texas	United States	75708
18	University of Wisconsin Hospitals and Clinics	Madison	Wisconsin	United States	53792