CXA-10 Study in Subjects With Pulmonary Arterial Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT04053543
• Date of registration: 19/07/2019
• Prospective Registration: Yes
• Primary sponsor: Complexa, Inc.
• Public title: CXA-10 Study in Subjects With Pulmonary Arterial Hypertension
• Scientific title: A Phase 2, Multi-Center, Open-Label Study to Evaluate Long-term Safety and Efficacy of CXA-10 in Subjects With Pulmonary Arterial Hypertension on Stable Background Therapy: Extension to Study CXA-10-301
• Date of first enrolment: August 9, 2019
• Target sample size: 33
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT04053543
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Theo Danoff, MD
• Affiliation: Complexa, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Evidence of a personally signed and dated informed consent document indicating subject
has been informed of all pertinent aspects of the study prior to initiation of any
study-required procedures.

2. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests
and other study procedures.

3. Has completed the CXA-10-301 study and demonstrated compliance with study medication
administration and study requirements.

4. If receiving simvastatin-containing products: simvastatin (Zocor), Vytorin, or any
other combination therapy containing simvastatin, simvastatin dose does not exceed 20
mg/day.

5. Currently receiving no more than three of the following previously approved PAH
therapies: phosphodiesterase type 5 (PDE-5) inhibitors, endothelin receptor
antagonists (ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids,
prostacyclin receptor agonists.

6. Women of childbearing potential and males with partners of childbearing potential must
agree to use a reliable method of contraception while taking study medication.

Exclusion Criteria:

1. Severe hypotension defined by systolic blood pressure <90 mmHg from sitting blood
pressure measurement at Baseline.

2. Hypertensive defined by >160 mmHg systolic or >110 mmHg diastolic from sitting blood
pressure measurement at Baseline.

3. QTcF on supine ECGs at Baseline (Visit 1) of >500 msec.

4. Acute myocardial infarction or acute coronary syndrome (ST-Elevation Myocardial
Infarction [STEMI], Non STEMI [NSTEMI] and or unstable angina) within the last 90 days
prior to Baseline.

5. Recent cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90
days prior to Baseline.

6. Recent hospitalization for left heart failure within the last 90 days prior to
Baseline.

7. Clinically significant aortic or mitral valve disease defined as greater than mild
regurgitation or mild stenosis; pericardial constriction; restrictive or constrictive
cardiomyopathy; left ventricular dysfunction (LVEF < 50%); left ventricular outflow
obstruction; symptomatic coronary artery disease; autonomic hypotension; or fluid
depletion, in the opinion of the investigator.

8. Chronic atrial fibrillation and life-threatening cardiac arrhythmias.

9. Personal or family history of congenital prolonged QTc syndrome or sudden unexpected
death due to a cardiac reason.

10. Clinically significant anemia in the opinion of the investigator that precludes
enrollment into this study, or Hb <9 gm/dl.

11. Severe hepatic impairment (Child-Pugh class C with or without cirrhosis) at Baseline
or active chronic hepatitis.

12. Received intravenous inotropes within 2 weeks prior to Baseline (e.g. dopamine,
dobutamine).

13. History of angina pectoris or other condition that was treated with long or short
acting nitrates <12 weeks of Baseline.

14. History of herbal or natural medication use (including fish oil) within 2 weeks or 5
half-lives, whichever is longer, prior to Baseline.

15. Received prednisone at doses > 15 mg/ day or changes in immunosuppressive medications
<12 weeks prior to Baseline.

16. Currently taking a drug that may affect the assay measurement of serum creatinine
(e.g. cimetidine, Bactrim, Pyridium). A list is provided in Appendix H.

21. Newly prescribed drug or increased dose of an existing drug that is known to prolong
the QTc interval and has been associated with Torsades de Pointes (TdP) identified in the
CredibleMeds.org website list as known risk (KR) of TdP.

Note: Stable doses of drugs classified as conditional risk (CR) of TdP or possible risk
(PR) of TdP are permitted (i.e., subject has received the same dose and regimen for at
least 30 days prior to Baseline with no anticipated changes to the dose or regimen during
the course of the study).

22. Currently taking dimethyl fumarate (Tecfidera™).

23. Any of the following laboratories abnormal and unresolved in CXA-10-301:

1. Absolute lymphocyte counts < 0.5 x 109 cells/L.

2. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3.0X upper
limit of normal (ULN), alkaline phosphatase (AP) > 2X ULN of liver origin, and total
bilirubin >2X ULN. If all liver function tests (LFTs) are within normal limits (WNL)
and total bilirubin is elevated, examination of direct and indirect bilirubin may be
conducted to evaluate for Rotor's/Gilbert's Syndrome. Subjects with Rotor's/Gilbert's
Syndrome may be enrolled.

3. eGFR < 30 mL/min/1.73 m2 (estimated by Chronic Kidney Disease Epidemiology
Collaboration [CKD-EPI] Creatinine/Cystatin C 2012 algorithm) at Baseline.

24. Females who are pregnant or breastfeeding, or who are trying to conceive. 25.
Recent (within 1 year) history of abusing alcohol or illicit drugs. 26. History of any
primary malignancy, including a history of melanoma or suspicious undiagnosed skin
lesions, or other malignancies (such as thyroid or testicular) that have been
curatively treated and with no evidence of disease for at least 3 years or prostate
cancer who is not currently or expected, during the study, to undergo radiation
therapy, chemotherapy, and/or surgical intervention, or to initiate hormonal
treatment.

Exception: subjects with history of basal cell or squamous cell carcinomas of the skin
or cervical carcinoma in situ are eligible for enrollment.

27. Cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic,
endocrine, metabolic, central nervous system or psychiatric disease that, in the
opinion of the investigator, may adversely affect the safety of the subject and/or
efficacy of the investigational product or severely limit the lifespan of the subject
other than the condition being studied.

28. Clinically significant hyperthyroidism or hypothyroidism not adequately treated.

29. Any other condition and/or situation that causes the Investigator to deem a
subject unsuitable for the study (e.g., due to expected study medication non-
compliance, inability to medically tolerate the study procedures, or a subject's
unwillingness to comply with study-related procedures).

30. Known hypersensitivity to CXA-10, the metabolites, or formulation excipients.

31. Treatment with any investigational drug (other than CXA-10) or device within 30
days or 5 half-lives (whichever is longer) prior to Baseline (this includes
investigational formulations of marketed products, inhaled and


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

PAH

Intervention(s)

Drug: CXA-10

Primary Outcome(s)

Incidence of AEs [Time Frame: 6 months]

Changes in blood pressure [Time Frame: 6 months]

Changes in respiration [Time Frame: 6 months]

Changes in heart rate [Time Frame: 6 months]

Secondary Outcome(s)

Who Classification of Functional Status [Time Frame: 6 months]

6 Minute Walk Distance [Time Frame: 6 months]

PAH-specific medication changes [Time Frame: 6 months]

Clinical worsening [Time Frame: 6 months]

Secondary ID(s)

CXA-10-2302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Innovative Analytics

Medpace, Inc.

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)