RECLAIM: an Adaptive Platform Trial for the Evaluation of Treatments for Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

20 Feb 2025 → ongoing

Decision date (initial)

2025-02-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ZonMW · Stichting Long Covid

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the impact of each IP vs. control on patient-reported physical health-related quality of life (HRQoL)

Secondary objectives 9

1. To determine the impact of each IP vs. control on patient-reported mental HRQoL, and on the seven PROMIS-29 domains individually
2. To determine the impact of each IP vs. control on patient-reported specific PASC symptoms: ● Fatigue ● Post-Exertional Malaise (PEM) ● Cognitive functioning ● Autonomic dysfunction
3. To determine safety of each IP in PASC patients.
4. To determine tolerability of each treatment in PASC patients.
5. To evaluate the durability of IP treatment responses.
6. Exploratory: Explore the above by PASC disease phenotype
7. Exploratory: Explore the above by pre-enrolment PASC symptom(s) duration
8. Exploratory: Investigate PASC pathophysiology and mechanisms of action of potential treatments.
9. Exploratory: Identify biomarkers for PASC symptom clusters and treatment(s)-associated recovery

Conditions and MedDRA coding

PASC: post-acute sequelae of SARS-CoV-2 infection

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adults aged 18 years or older.
2. Residing in the study area (defined in each respective CSA) for the duration of trial participation.
3. Persistent PASC signs and symptoms, including fatigue and/or PEM, for a period of at least 12 weeks after the onset of a SARS-CoV-2 infection. The symptoms were not present prior to the infection, but may have partially subsided and resurged after the infection.
4. Self-reported confirmation of having had a SARS-CoV-2 infection by: a. Positive SARS-CoV-2 nucleic acid amplification test (NAAT), such as PCR; b. Positive SARS-CoV-2 rapid diagnostic test, including home-administered tests; c. COVID-19 diagnosis by a treating physician (GP or medical specialist), based on the above or other clinical tests and assessments. Alternatively, a treating physician may have diagnosed the patient with PASC, thereby implicitly acknowledging that the patient had COVID-19 in the past.
5. Willing and able to provide informed consent
6. Willing and able to perform trial procedures
7. Allowing their GP/pharmacy and the RECLAIM trial team to exchange medical information that is relevant for the participant’s safety and trial assessments.

Exclusion criteria 6

1. Having been diagnosed with (exacerbation of) a chronic disease that can account for the onset of the PASC-like symptoms.
2. Being hospitalised or institutionalised at screening. Patients can be rescreened after discharge.
3. Presence of a serious medical condition that would prevent completion of follow-up.
4. Currently enrolled, or having been enrolled within the last 30 days, in any other study where that study’s interventions or procedures may affect RECLAIM outcomes or procedures. Individuals can be rescreened after at least 30 days have passed since participation in such a study has been completed.
5. Having initiated chronic use of a new licensed medication for any indication in the three months prior to the eligibility confirmation by a trial physician. This criterion may be reassessed after sufficient time has passed. Similarly, the potential participant should commit to not starting any chronic use of new licensed medications for any indication between eligibility confirmation and Week-12 unless medically necessary as determined by a treating physician (see section 8.1.1.1).
6. The following exclusion criteria will apply to all potential participants WITHIN ONE TRIAL DOMAIN (these patients may still qualify for another trial domain): 6 The participant cannot be randomised to at least one IP arm and its control arm within a trial domain due to (refer to relevant TSAs for details): a. Known hypersensitivity to an active IP ingredient or IP/placebo excipient; b. Receiving a treatment that is contraindicated to a trial IP; c. Already using a trial IP, or a drug in the same drug class as a trial IP, outside of the trial; d. Any other reason why a trial IP cannot be used, such as (risk of) pregnancy or breastfeeding or renal insufficiency.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Assessed at 12 weeks (end of trial product use period): Patient-Reported Outcomes Measurement Information System Profile29 (PROMIS-29) physical health summary score

Secondary endpoints 9

1. Assessed at 12 weeks: ● PROMIS-29 mental health summary score ● PROMIS-29 domain scores: physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, sleep disturbance.
2. Assessed at 12 weeks: ● Checklist Individual Strength (CIS-8) ● DePaul Symptom Questionnaire (DSQ-2) PEM questions ● PROMIS cognitive function 8a ● DSQ-2 POTS questions
3. Assessed at 12 weeks: ● Frequency of related and unrelated (S)AEs in each IP arm compared to its control arm including their severity and outcome.
4. Assessed at 12 weeks: ● Level of adherence to each IP versus the matching placebo control (if available). ● Percent of participants with adequate adherence for the specific IP.
5. Assessed at 24 weeks (12 weeks after cessation of IP use): The proportion of participants that maintain HRQoL treatment success at 12 weeks.
6. Exploratory: Same as above but stratified by phenotype.
7. Exploratory: Same as above but stratified by pre-enrolment PASC symptom(s) duration.
8. Exploratory: Described in relevant TSAs.
9. Exploratory: Described in relevant TSAs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Janneke van de Wijgert

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Janneke van de Wijgert

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications