Clinical trial NCT04708340: Tolerability and Efficacy of RJX in Patients With COVID-19
Official title: A Two-part, Two-cohort, Double-blind, Randomized, Placebo-controlled, Multicenter Phase 1/2 Study to Evaluate the Safety, Tolerability and Efficacy of REJUVEINIX (RJX) in Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: COVID-19
Acute Respiratory Distress Syndrome
SARS-CoV-2
Hypoxemia
Lead sponsor: Reven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-13
Enrollment: 237
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In Part 1, RJX will be administered daily for 7 days (1 cycle). In Part 2, Placebo or RJX will be administered daily for 7 days for 1 cycle but may receive 2 cycles.

Each Cohort is comprised of Part 1, a single site, and Part 2, multiple sites. The 2 Cohorts are:

Cohort 1:

* Hospitalized COVID-19 patients ≥18 years without hypoxemia and either not receiving any oxygen therapy OR are receiving supplemental oxygen via mask or nasal prongs (clinical status score 4 or 5 on 8-point ordinal scale).
* Patients are required to have the following high-risk characteristics

  * Age ≥65 years AND type 2 diabetes or hypertension OR
  * Age ≥18 years with abnormal blood tests AND CRP \>50 mg/L PLUS at least 1 of the following biomarkers abnormal: a. D-dimer, b. Ferritin, c. High sensitivity cardiac troponin, d. LDH

Cohort 2:

• Hospitalized COVID-19 patients with hypoxemia and without ARDS who are receiving either non-invasive positive pressure ventilation (NIPPV) OR high flow oxygen
Primary purpose: TREATMENT

Brief summary: This study is designed as a 2-part, 2-cohort, double-blind, randomized, placebo controlled, multicenter Phase 1/2 study to evaluate the safety, tolerability and efficacy of RJX in patients with COVID-19.

Detailed description: For each cohort, there will be an open label Safety Lead-in (Part 1) and a placebo controlled, randomized, double-blind portion (Part 2). In Part 1, RJX will be administered daily for 7 days. In the active treatment arm of Part 2 for both cohorts, RJX will be administered daily for 7 days per cycle and patients may receive up to 2 cycles. As detailed below, patients will be allowed to receive a second 7 day cycle of therapy based on the medical judgment of the Investigator. The total RJX exposure during Part 2 could therefore be up to 14 days. Both cohorts will start and enroll in parallel and independently. A safety follow-up period will begin at Day 14/Discharge, or when treatment is discontinued, and will continue for approximately 60 days post discharge. Part 1 will be conducted at a single site and Part 2 will be conducted at multiple sites. The 2 cohorts in this study are:

* Cohort 1:

  * Hospitalized COVID-19 patients ≥18 years without hypoxemia who are either not receiving any oxygen therapy OR are receiving supplemental oxygen via mask or nasal prongs (namely, clinical status score 4 or 5 on an 8-point ordinal scale).
  * Patients are required to have the following high-risk characteristics

    1. Age ≥65 years AND type 2 diabetes or hypertension OR
    2. Age ≥18 years with abnormal blood tests AND CRP \>50 mg/L PLUS at least 1 of the following biomarkers:

       1. D-dimer \>1,000 ng/mL,
       2. Ferritin \>500 µg/L,
       3. High sensitivity cardiac troponin \>2 × upper limit of normal (ULN),
       4. LDH \>245 U/L.
* Cohort 2:

  * Hospitalized COVID-19 patients with hypoxemia without ARDS who are receiving either non-invasive positive pressure ventilation (NIPPV) OR high flow oxygen (namely, clinical status score 3 on an 8-point ordinal scale).

Eligibility criteria: Inclusion Criteria

Cohort 1 (Part 1 and Part 2):

1. Hospitalized COVID-19 patients ≥18 years without hypoxemia who are either not receiving any oxygen therapy OR are receiving supplemental oxygen via mask or nasal prongs (namely, clinical status score 4 or 5 on an 8-point ordinal scale)
2. Hospitalized COVID-19 patients age ≥65 years AND type 2 diabetes or hypertension, OR
3. Hospitalized COVID-19 patients ≥18 years AND abnormal blood tests with CRP \>50 mg/L PLUS at least 1 of the following biomarkers:

   1. D-dimer \>1,000 ng/mL
   2. Ferritin \>500 µg/L
   3. High sensitivity cardiac troponin \>2 × ULN
   4. LDH \>245 U/L

   Cohort 2 (Part 1 and Part 2):
4. Hospitalized COVID-19 patients with hypoxemia who are either receiving NIPPV OR high-flow oxygen (namely, clinical status score 3 on an 8-point ordinal scale).
5. Bilateral opacities on a chest x-ray OR chest CT scan. Cohort 1 and Cohort 2 (Parts 1 and 2)
6. Male and non-pregnant, non-lactating female patients with SARS-CoV-2 infection that is documented by a Food and Drug Administration (FDA)-authorized diagnostic reverse transcription polymerase chain reaction test at/or within 4 days of Screening
7. ≥18 years of age
8. Body weight ≥40 kg at Screening
9. History of COVID-19 within the last 2 weeks prior to study enrollment
10. The patient OR a legally authorized representative has provided written informed consent
11. Females of childbearing potential must have a negative beta human chorionic gonadotropin pregnancy test at Screening
12. Females of childbearing potential must agree to be abstinent or else use a medically acceptable form of contraception from the Screening period through Day 28. Medically acceptable forms of contraception including implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomy, and double-barrier method \[condom and occlusive cap (diaphragm or cervical/vault caps)\] with spermicidal foam/gel/film/suppository

Exclusion Criteria Cohort 1

1. Receiving high-flow oxygen OR NIPPV. Cohort 1 and Cohort 2
2. ARDS by Berlin definition (Appendix 16.2)
3. On extracorporeal membrane oxygenation
4. Uncontrolled hypertension (systolic blood pressure \[BP\] \>150 mmHg and/or diastolic BP \>100 mmHg), unstable angina, congestive heart failure of New York Heart Association Classification Class III or IV (i.e., Class III: marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g., walking short distances \[20 100 m\], comfortable only at rest; Class IV: severe limitations, experiences symptoms even while at rest, mostly bedbound patients), serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 12 months prior to enrollment
5. Subjects with a history of congenital long QT syndrome or of Torsades de pointes; subjects with bradycardia (\<60 bpm), heart block (excluding 1st degree block, being PR interval prolongation only); subjects with any of the following findings on electrocardiogram (ECG): QTc interval \>470 msec in women OR \>450 msec in men; subjects requiring any drugs known to prolong the QTc interval, including antiarrhythmic medications
6. Shock or hypotension requiring vasoactive peptides, such as dopamine, norepinephrine, epinephrine, or dobutamine
7. Renal function impairment with creatinine ≥2 mg/dL
8. Liver function impairment with total bilirubin ≥2 mg/dL
9. Platelet count \<50,000/µL
10. Multi-organ failure
11. History of an allergic reaction or hypersensitivity to the study drug or any component of the study drug formulation
12. Use of systemic corticosteroids, nonsteroidal anti-inflammatory drugs, antibiotics, and antiviral drugs that are not part of the standard of care
13. Presence of any uncontrolled concomitant illness (e.g., bacterial sepsis or invasive fungal infection), or other serious illness and medical conditions, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with their participation in the study
14. Pregnancy or breast-feeding (for women)

Primary outcomes:
measure: Safety as measured by DLTs and drug related SAE's
timeFrame: Up to 60 days post-enrollment
measure: Tolerability and Efficacy measured by progression of disease through an ordinal scale.
timeFrame: Within 2 weeks
measure: Efficacy measured by time to resolution of respiratory failure
timeFrame: 60-days post enrollment
Secondary outcomes:
measure: Efficacy as measured by day of ICU care.
timeFrame: 60-days post enrollment
measure: Safety, Tolerability, Efficacy measured by mortality over 28 Days.
timeFrame: 28-days post enrollment
measure: Efficacy measured by mean change in baseline clinical status on Days 7 and 14.
timeFrame: 14-days post enrollment
measure: Efficacy measured by mean change in hospitalization days on Days 7 and 14.
timeFrame: 14-days post enrollment
measure: Efficacy measured by time to coming off supplemental oxygen on Days 7 and 14.
timeFrame: 14-days post enrollment
measure: Safety and Efficacy measured by time from first dose to renal therapy.
timeFrame: 60-days post enrollment
Other outcomes:
measure: Evaluate Change in Serum CRP Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum Ferritin Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum D-dimer Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum LDH Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum IL-6 Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum IL-10 Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum TNF-α Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum TGF-β Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum C3 Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Serum C5 Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in Plasma ascorbic acid Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in plasma niacinamide Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in plasma thiamine Concentration
timeFrame: Up to 28-days post randomization
measure: Evaluate Change in plasma cyanocobalamin Concentration
timeFrame: Up to 28-days post randomization
Locations:
city: Houston
country: United States
facility: Memorial Hermann Memorial City Medical Center
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Southeast Hospital
state: Texas
city: New Braunfels
country: United States
facility: Christus Santa Rosa Hospital
state: Texas
Study officials:
References: