A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19 / Other LRTI

NCT05348772 | Completed Phase 1

• 1 other identifier: AmnioPul-02-001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human (FIH), Phase 1b, open-label, dose-escalation, safety trial consisting of 3 dose levels. Subjects will always be treated in cohorts of size 3, with from 3 up to 6 cohorts i.e. 9-18 subjects.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Dose-limiting adverse events/toxicities (DLTs)

  The primary endpoint is the number of subject dose-limiting adverse events/toxicities (DLTs) associated with administration of AmnioPul-02 at each dose level.

  Day 7

Secondary Outcomes (6)

• OS

  Day 22

• Event-free survival

  Day 22

• Ventilator-free days

  Day 22

• Time to clinical response

  Day 22

• OS

  1 year

Study Arms (2)

AmnioPul-02 Dose level 1

ACTIVE COMPARATOR

AmnioPul-02 Dose level 1

Drug: AmnioPul-02

AmnioPul-02 Dose level 2

ACTIVE COMPARATOR

AmnioPul-02 Dose level 2

Drug: AmnioPul-02

Interventions

AmnioPul-02 DRUG

Mesenchymal stem / stromal cells, MSC

AmnioPul-02 Dose level 1; AmnioPul-02 Dose level 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects ≥18 to ≤80 years of age with a diagnosis of moderate or severe COVID-19, with or without pneumonia, as follows:
• SARS-CoV-2 infection, as confirmed by RT-PCR test within 72 hours before dosing.
• Subjects hospitalised primarily due to COVID-19, with symptoms considered typical for COVID-19 (eg, fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, shortness of breath, or dyspnoea requiring oxygen treatment).
• A score of 4, 5, or 6 on the NIAID 8-point ordinal scale for COVID-19 severity, as follows (Beigel et al 2020, Appendix II):
• i. Score 4: Hospitalised, not requiring supplemental oxygen, but requiring ongoing medical care (related to COVID-19 or to other medical conditions). ii. Score 5: Hospitalised, requiring any supplemental oxygen. iii. Score 6: Hospitalised, requiring non-invasive ventilation or use of high-flow oxygen devices.
• Willing and able to give written informed consent prior to the initiation of any trial procedure.
• For females only: At the time of enrolment, negative beta human chorionic gonadotropin (β-hCG) pregnancy test (serum) for women of childbearing potential (WOCBP). A woman will be considered WOCBP following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
• A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• If the subject is a WOCBP, must agree to practice highly effective method of contraception from screening visit and until 30 days after the last investigational medicinal product (IMP) administration. Highly effective methods of contraception include: a. Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: i. Oral ii. Intravaginal iii. Transdermal b. Progestogen-only hormonal contraception associated with inhibition of ovulation: i. Oral ii. Injectable iii. Implantable c. Intrauterine devices d. Intrauterine hormone-releasing system e. Bilateral tubal occlusion f. Vasectomized partner g. Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial treatments. The reliability of sexual abstinence needs to be evaluated in relation to the preferred and usual lifestyle of the subject) Note: Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective contraceptive methods.

You may not qualify if:

• Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment in this trial (subjects who are in a follow-up period of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent).
• Life expectancy \<72 hours, in the opinion of the Investigator.
• Subjects requiring invasive mechanical ventilation or ECMO.
• Subjects on non-invasive CPAP ventilation or HFNO (score 6 of the NIAID 8-point ordinal scale for COVID-19 severity; Beigel et al 2020, Appendix II) are allowed, but will be excluded if they have moderate to severe ARDS (eg, same day ratio of arterial partial pressure of oxygen to fraction of inspired oxygen \[PaO2/FiO2\] ≤200 mmHg; or oxygen saturation \[SpO2\]/FiO2 ≤232 if arterial blood gas test is not available).
• Active known cancer disease, except subjects with nonaggressive cancers such as basal cell carcinoma, or cervical carcinoma in situ.
• Clinical evidence of active infection, in addition to the SARS-CoV-2 infection, including influenza.
• Body weight \>120 kg.
• Pregnant or breastfeeding female subject.
• Alzheimer's disease or dementia or any other medical condition that, in the opinion of the investigator, impact the subject's capability to properly consent with trial participation or to comply with trial protocol procedures.
• Signs of disseminated intravascular coagulation as per the investigator's medical judgement based on the symptoms of the subject, such as unexplained bleeding, along with subject's laboratory parameters including platelet count, prothrombin time-international normalised ratio (PT-INR), partial thromboplastin time (PTT), plasma fibrinogen, and plasma D-dimer.
• Creatinine clearance \<30 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.
• Abnormal liver chemistry, defined as ALT or aspartate aminotransferase (AST) or total bilirubin or PT-INR \>1.5 × upper limit of normal (ULN).
• Severe cardiovascular diseases (severe or unstable angina, congestive heart failure (New York Heart Association \[NYHA\] III-IV), myocardial infarction within past 1 year, uncontrolled hypertension, and uncontrolled arrhythmia).
• Electrocardiogram (ECG) findings with corrected QT interval using Fridericia's (QTcF) formula \>500 msec.
• Subjects with a known or suspected hypersensitivity to MSCs or contaminants (DMSO and Accutase).

Sponsors & Collaborators

• Amniotics AB: lead

Study Sites (1)

Infection clinic

Malmo, Skåne County, 21428, Sweden

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential Cohorts

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: April 27, 2022
• Study Start: October 10, 2022
• Primary Completion: February 9, 2023
• Study Completion: February 9, 2023
• Last Updated: March 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)