| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 25.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10087832 |
| E.1.2 | Term | COVID-19 rebound |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare efficacy of BC 007 (double dose 1350 mg and double dose 1900 mg) with placebo based on fatigue symptomatic severity scale in long COVID participants. |
|
| E.2.2 | Secondary objectives of the trial |
To compare GPCRAAB neutralizing effect of BC 007 1350 mg with that of placebo.
To compare GPCRAAB neutralizing effect of BC 007 1900 mg with that of placebo.
To compare GPCR‑AAB neutralizing effect of BC 007 1350 mg with that of BC 007 1900 mg
To compare efficacy of BC 007 (double dose, 1350 mg or 1900 mg) with placebo including patient outcome measures, and symptoms in participants with long COVID.
To compare efficacy of BC 007 (double dose, 1350 mg or 1900 mg) with placebo based on symptoms (as assessed by COA symptom diary) in participants with long COVID
To compare efficacy of BC 007 (double dose, 1350 mg or 1900 mg) with placebo based on performance levels in participants with long COVID
To compare safety and tolerability of BC 007 (double dose, 1350 mg or 1900 mg) with respective placebo after two infusions separated by a 14-day interval (treatment phase)
To assess the viral load in faeces
To assess blood coagulation
Blood sedimentation rate
Quality of life
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. The participant provides written informed consent prior to any clinical study-specific procedures.
2. The participant is a male or female, ≥18 years of age, at the time of signing the informed consent form.
3. All male and female participants of childbearing potential must be willing to use effective methods of contraception from the start of Screening until EOS (Day 90). Male participants must refrain from donating sperm during this period.
4. Acute phase of COVID-19 ended at least 3 months prior to dosing.
5. The participant has a confirmed negative SARS-CoV-2 test result (polymerase chain reaction [PCR] test) at screening.
6. The participant provides a documented positive SARS-CoV-2 test result (reverse transcriptase [RT]-PCR or rapid antigen test) at Screening. For participants with long COVID symptoms who cannot provide certified evidence, a positive antibody test for nucleocapsid protein IgG must demonstrate a history of SARS-CoV-2 infection; this test can be performed as part of the Screening procedure. The participant reports persistence or new onset of symptoms after a SARS- CoV-2 infection, with these symptoms lasting for at least 2 consecutive months (being persistent, recurrent, or of varying severity within that period) with no other explanation, as defined by WHO, and not being present prior to COVID-19 infection.
7. Participant is screened positive for GPCR-AAB activity by Berlin Cures laboratory.
8. Participant has not been intubated or received ECMO support during their acute COVID-19 infection.
9. Participant screens positive for fatigue (FACIT-FS score <35) and presents with at least one additional symptom from the symptom score sheet (COA) which has persisted for more than 12 weeks.
10. Participant is not on any permanent medication(s) to treat chronic diseases that existed prior to COVID19 infection. Exceptions are clinically stable conditions, which do not affect the study assessments and may be allowed as judged by the Investigator after discussion with the medical monitor. Clinically unstable is defined as a diagnosis or condition requiring changes in disease management within 2 months prior to start of Screening and includes ongoing workup of an
undiagnosed illness that could lead to a new diagnosis or condition.
Concomitant treatment may be permitted if:
• A treatment (type and dose) remained unchanged within the 2 months
before the start of Screening.
• No change in treatment is expected or required between Screening
visit and Day 30 of the study.
• A treatment does not affect any of the study assessments, in particular
by (e.g.,) causing fatigue or by impairing concentration ability.
As judged by the Investigator and after discussion with the medical
monitor, possible allowed concomitant medications include but are not
limited to:
• Antihypertensives (β-blockers are NOT allowed)
• Lipid lowering agents.
• Antidiabetics (insulin is NOT allowed)
• Thyroid hormone replacement.
• Topical treatments
• Low dose acetylsalicylic acid (up to 100 mg/day).
• Ivabradine
11. Participant reports that his/her activity level was not impaired prior to acute COVID-19 infection. |
|
| E.4 | Principal exclusion criteria |
1. Postural Orthostatic Tachycardia Syndrome existing prior to the initial SARS-CoV-2 infection leading to long COVID, as per medical history. History or evidence of any clinically significant cardiovascular disease.
2. Any history or presence of a major gastrointestinal, endocrinologic (e.g., insulin-dependent diabetes), cardiovascular, hematologic, hepatic, immunologic, metabolic (specifically gout), urologic, pulmonary (e.g., allergic or intrinsic asthma), neurologic, dermatologic, renal and/or other major disease, as judged by the Investigator. Other clinically stable conditions, which do not affect the study assessments may be allowed as judged by the Investigator after discussion with the medical monitor.
Possible allowed diseases are (if stable and well-controlled) include but are not limited to:
• Respiratory disorders (e.g., asthma-like) that first appear with long COVID.
• Mild hypertension (<160 mmHg systolic, <100 mmHg diastolic)without known organ or vessel damage.
• Non-insulin-dependent diabetes mellitus without known organ or vessel damage.
• Glaucoma.
• Hypercholesterolemia/hypertriglyceridemia.
• Hypothyreosis.
3. Participants with history of major active or chronic unstable psychiatric illness (e.g., but not limited to, depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year.
4. Any history of any other chronic neurological, or psychological disease such as, but not limited to, chronic fatigue syndrome, fibromyalgia,systemic lupus erythematosus, Sjogren's syndrome. Any history or presence of relevant allergic reactions (e.g., requiring hospital stay, intravenous [i.v.] treatment or treatment with systemic steroids). A participant will not be included if it is likely that seasonal allergic symptoms will require any kind of systemic treatment until Day 30 of the study.
5. Participant has a history of hypersensitivity to the study intervention or any of the excipients or to medicinal products with similar chemical structures.
6. Participant has any other condition, which in the opinion of the Investigator precludes the participant’s participation in the clinical study.
7. Participant shows clinically significant abnormalities in clinical chemistry or haematology at screening, as judged by the Investigator; additionally, a participant will not be included if the laboratory shows at least one of the following results at Screening:
• Thrombocytes <100.000/µL.
• Hb <lower limit of normal (LLN) −10%.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST),gamma glutamyl transferase (GGT) >2× upper limit of normal (ULN).
• International normalized ratio (INR) >1.2.
8. Female participant is pregnant and/or breast feeding.
9. Participant participated in a previous clinical study (within 30 days or 5 half-lives of the investigational drug, whichever is longer prior to start of Screening) or concomitant participation in another clinical study with investigational medicinal product(s) or device(s), or participant previously participated in this study and received study intervention.
10. Participant is an employee of the Sponsor, or contract research organization (CRO) conducting the study.
11. Participant has a close affiliation with the investigational site, e.g., a close relative of the Investigator, dependent person (e.g., employee or student of the investigational site).
12. Participant with an estimated glomerular filtration rate <60 mL/min/1,73 m².
13. Participant has alcohol addiction or history of alcohol addiction.
14. Participant has drug addiction or history of drug addiction.
15. Any psychological, emotional problems, any disorders or resultant therapy that is likely to invalidate informed consent or limit the ability of the participant to comply with the protocol requirements.
16. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the last 5 years.
17. Participant has had comparable and prolonged symptoms after other viral infections (e.g., after Epstein-Barr virus infection, influenza, infectious mononucleosis).
18. Previous diagnosis of sleep apnoea.
19. Current use of medications with psychoactive properties that have a deleterious effect on cognition. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Mean change from baseline in score on FACIT-FS at Day 30. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Proportion of participants sero-converting to negative for GPCR-AAB at Day 3, Day 15, Day 17, Day 30, Day 60, and Day 90 post first infusion of study intervention.
The below outcome measures will be assessed at the following times:
-Day 1 (baseline, all assessments)
-Day 3 (COA symptom diary)
-Day 15 (pre-dose, all assessments)
-Day 17 (COA symptom diary)
-Day 30 (all assessments; FACIT-F is primary end point)
-Day 60 (all assessments)
-Day 90 (all assessments)
Results will be reported as:
-Mean change from baseline in score on FACIT-FS.
-Proportion of subjects with an increase from baseline in FACIT-FS score of at least 6
-Proportion of subjects with an increase from baseline in FACIT-FS score of at least 3.
-Proportion of subjects with a FACIT-FS score greater than 34
-Mean change from baseline in cognitive impairment as measured by PDQ assessing attention/focus, retrospective and prospective memory, planning and organization ability.
-Mean/median change from baseline in symptoms score calculated as sum of symptom scores/number of symptoms scored on Day 3, Day 15, Day 17, Day 30, Day 60, and Day 90.
-Mean change from baseline in hours slept in the past 24 hours as measured by the sleep item as part of the COA symptom diary score sheet, reported on Day 15, Day 30, Day 60, and Day 90.
-Mean change from baseline for the tiredness whilst being awake reported on the tiredness item as part of the COA symptom diary score sheet on Day 15, Day 30, Day 60, and Day 90.
-Mean change in baseline on the quality of sleep reported on the quality of sleep item on Day 15, Day 30, Day 60, and Day 90.
-6 MWT at Day 1, Day 3, Day 15, Day 17, Day 30, Day 60, and Day 90.
-Evaluation of the safety of study intervention at Screening visit, during administration of study intervention, and during outpatient periods until the end of the treatment phase assessed at Day 3 and Day 15, the follow up period assessed at Day 17, Day 30, Day 60, and Day 90.
-Monitoring of haematology and coagulation parameters, blood chemistry, urinalysis (safety laboratory measurements), vital signs, physical examination including body weight as assessed at screening visit, Day 1 (pre-and post-dose), Day 3, Day 15 (pre-dose and post-dose), Day 17 and Day 30; and during the extended follow up phase at Day 60 and Day 90.
-12-lead electrocardiogram (ECGs) to be assessed at screening visit, Day 1 (pre- and post-dose), Day 15 (pre- and post-dose), Day 30, Day 60 and Day 90.
-All AEs and SAEs as well as recording of concomitant medications/significant non-drug therapies from signing of informed consent form until study completion.
-Faecal sampling in subgroup at 2 centres: persisting viral load (difference between before dosing and 30 days after dosing) at Day 1 (pre-dose) and on Day 30.
-Haptoglobin, D-dimers, fibrinogen at screening, Day 3, Day 17 and Day 30.
-Blood sedimentation rate at Screening, Day 1 (pre-dose), Day 3, Day 15 (pre-dose), Day 17, and Day 30.
-EQ 5D QoL questionnaire at Day 1 (pre-dose), Day 15 (pre-dose), Day 30, Day 60, and Day 90. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please see in the appropriate endpoints themselves in section E.5.2. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Switzerland |
| Austria |
| Finland |
| Germany |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
