Strona Badania kliniczne Nct

Summary
EudraCT Number:2022-003452-14
Sponsor's Protocol Code Number:SBC007C401
National Competent Authority:Germany - BfArM
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-11-21
Trial results
A. Protocol Information
A.1Member State ConcernedGermany - BfArM
A.2EudraCT number2022-003452-14
A.3Full title of the trial
A prospective, double-blind, randomised, parallel group, placebo controlled, multicentre, Phase II study to investigate the efficacy, GPCR autoantibody neutralising effect, safety, and tolerability of BC 007 in participants with long COVID
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
To investigate efficacy, pharmacodynamics, and safety of BC 007 in participants with long COVID
A.3.2Name or abbreviated title of the trial where available
BLOC
A.4.1Sponsor's protocol code numberSBC007C401
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorBerlin Cures GmbH
B.1.3.4CountryGermany
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportBerlin Cures GmbH
B.4.2CountryGermany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationBerlin Cures GmbH
B.5.2Functional name of contact pointClinical Trial Department
B.5.3 Address:
B.5.3.1Street AddressKnesebeckstr 59-61
B.5.3.2Town/ cityBerlin
B.5.3.3Post code10719
B.5.3.4CountryGermany
B.5.4Telephone number+49308891364050
B.5.5Fax number+4932121289797
B.5.6E-mailclinical@berlincures.de
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameBC 007
D.3.2Product code BC 007
D.3.4Pharmaceutical form Powder for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNNAP
D.3.9.1CAS number 145563-68-4
D.3.9.2Current sponsor codeBC 007
D.3.9.3Other descriptive named(GGTTGGTGTGGTTGG), GS-522, ARC183, anti-thrombin aptamer (TBA), HTQ,HD1
D.3.9.4EV Substance CodeSUB267654
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number50
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboSolution for infusion
D.8.4Route of administration of the placeboIntravenous use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
long Covid
E.1.1.1Medical condition in easily understood language
long Covid
E.1.1.2Therapeutic area Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 25.1
E.1.2Level LLT
E.1.2Classification code 10087832
E.1.2Term COVID-19 rebound
E.1.2System Organ Class 10021881 - Infections and infestations
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main 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.2.2Secondary 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
Quality of life
E.2.3Trial contains a sub-study No
E.3Principal 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 during the intervention period, and at least 6 months from the time of receiving the last dose of the study intervention. 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
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.
11. Participant reports that his/her activity level was not impaired prior to acute COVID-19 infection.
E.4Principal 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 longCOVID.
• Mild hypertension (<160 mmHg systolic, <100 mmHg diastolic)without known organ or vessel damage.
• Non-insulin-dependent diabetes mellitus without known organ orvessel 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 and on Day 1 (Visit 2) pre-dose:
• 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).
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.5.1Primary end point(s)
Mean change from baseline in score on FACIT-FS at Day 30.
E.5.1.1Timepoint(s) of evaluation of this end point
Day 30
E.5.2Secondary end point(s)
Proportion of participants sero-converting to negative for GPCR-AAB at Days 3, 15, 17, 30, 90, 180 and Day 360 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)
-Day 180 (all assessments)
-Day 270 (all assessments)
-Day 360 (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 Days 3, 15, 17, 30, 60, 90, 180, 270 and 360.
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, Day 90, Day 180, Day 270, and Day 360.
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, Day 90, Day 180, Day 270, and Day 360.
Mean change in baseline on the quality of sleep reported on the quality of sleep item on Day 15, Day 30, Day 60, Day 90, Day 180, Day 270 and Day 360.
6MWT at Day 1, Day 3, Day 15, Day 17, Day 30, Day 60, Day 90, Day 180, Day 270, and Day 360.
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 initial followup period assessed at Day 17 and Day 30; and during the extended follow up phase at Day 60, Day 90, Day 180, Day 270, and Day 360.
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, Day 90, Day 180, Day 270, and Day 360.
12-lead electrocardiogram (ECGs) to be assessed at screening visit, Day 1 (pre- and post-dose), Day 15 (pre- and post-dose), Day 30, and during the extended follow-up phase at Day 60 and Day 180.
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.
Blood sedimentation rate at screening, Day 1 (pre-dose) and on Day 3, D15 (pre-dose), D17 and D30.
Thromboelastography in subgroup at 2 centres at Day1 (pre-dose), Day 15 (pre-dose) and on Day 30.
Haptoglobin, D-dimers, fibrinogen at screening, Day 3, Day 17 and Day 30.
EQ5D QoL questionnaire at Day 1 (pre-dose), Day 15 (pre-dose) and Day 30, and during the extended follow up phase at Day 60, Day 90, Day 180, Day 270 and Day 360.
E.5.2.1Timepoint(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.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial4
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.8.4.1Number of sites anticipated in Member State concerned9
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA15
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If 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.8.7Trial 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
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months6
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years2
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 100
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 14
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state53
F.4.2 For a multinational trial
F.4.2.1In the EEA 90
F.4.2.2In the whole clinical trial 114
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
None
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-02-09
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-05-02
P. End of Trial
P.End of Trial StatusOngoing
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