Sickle Cell Disease
Conditions
Keywords
Hb-SS, Hb S/β0-Thal
Brief summary
This multicenter, randomized, double-blind, parallel-group, placebo-controlled pilot study evaluated the safety, tolerability, and exploratory efficacy of orally administered NUV001 in adult participants with sickle cell disease (HbSS or HbSβ0 genotypes). A total of 168 participants were randomized in a 1:1:1 ratio to receive NUV001 immediate-release (IR), NUV001 gastro-resistant (GR), or placebo, in addition to standard of care, for 90 days over 5 study visits. The primary objective was to assess safety and tolerability based on adverse events, clinical laboratory safety parameters, and vital signs. Exploratory secondary objectives evaluated hematologic, hemolysis, and patient-reported outcomes.
Detailed description
This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled pilot study conducted in adult participants with sickle cell disease. Participants were randomized in a 1:1:1 ratio to one of three treatment groups: 1. NUV001 immediate-release (IR) 2. NUV001 gastro-resistant (GR) 3. Matching placebo All treatments were administered orally in addition to standard of care for 90 days. The study was designed to evaluate safety and tolerability, including adverse events, clinical laboratory safety parameters, and vital signs. Exploratory objectives included evaluation of hematologic parameters, markers of hemolysis, and patient-reported outcomes related to pain and quality of life. The study was conducted as a pilot, feasibility, and design-informing clinical study.
Interventions
DIETARY_SUPPLEMENTNUV001 - IR
Daily supplementation with 1000 mg of NUV001 (in two administration orally) immediate release gel capsule formulation for 90 days in total.
DIETARY_SUPPLEMENTNUV001 - GR
Daily supplementation with 1000 mg of NUV001 (in two administration orally) gastro resistant gel capsule formulation for 90 days in total.
DIETARY_SUPPLEMENTPlacebo
Placebo containing starch Powder (1000 mg, daily in two administration orally for 90 days).
Sponsors
LGD
ProRelix Research
Nuvamid SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Men or women over 18 to 65 years, both inclusive. 2. Non-smokers. 3. BMI \> 18 kg/m2 4. Patients diagnosed with sickle cell disease (documented by haemoglobin electrophoresis) and carrying SS or Sbeta0 versions of the beta globin gene (documented by genotyping, known through medical history). 5. Haemoglobin levels between 5.5 and 10.5 g/dl during Screening (for newly diagnosed or patients not on any treatment for SCD). 6. If the patient has been treated with an anti-sickling agent within three months of the Screening visit, the therapy must have been continuous for at least three months with the intent to continue for the duration of the study. 7. Available to attend on an outpatient basis for visits provided for in the protocol and able to complete the data collection documents (compliance and quality of life scale) 8. Patient or the patient's legally authorized representative has given written informed consent.
Exclusion criteria
1. Patients with known or suspected allergy to any ingredient of the food supplement 2. Patient having consumed vitamin or food supplements containing NAD+ precursors (niacin, tryptophan, nicotinamide, NMN, NR etc...) during the month before selection. 3. Patient has a significant medical condition that required hospitalization (other than sickle cell crisis) within two months of the screening visit. 4. Patient has prothrombin time INR \> 2.0. 5. Patient has serum albumin less than 3.0 g/dl. 6. Patient has received any blood products within three months of the Screening visit. 7. Patients hospitalized for acute vaso-occlusive crisis within one month of the Screening visit. 8. Patient has clinically significant, cardiovascular or liver disease or renal insufficiency or lymphopenia , evident in medical history (with clinically significant abnormal results on the Screening bioassays for eg.: Complete blood count, Aspartate transaminases, Alanine transaminases, Gamma glutamyl transferase, Alkaline Phosphatase, Bilirubin, Creatinine, Creatinine Phosphokinase, Blood Glucose, HbA1c, Lipid Profile). 9. Patient with diagnosed cancer in the past 2 years. 10. Patients participating simultaneously in another clinical research protocol or having recently participated in another research for which the exclusion period has not been completed. 11. Pregnant, lactating or parturient women. 12. Persons deprived of their liberty by a judicial or administrative decision, hospitalized without consent or admitted to a health or social establishment for purposes other than that of research. 13. Majors under legal protection or unable to express their consent. 14. People in an emergency situation unable to express their prior consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events through Day 90. | Baseline to Day 90 | Subject incidence of treatment-emergent adverse events through the treatment period. |
| Change from baseline in hematologic and biochemical safety parameters at Day 90. | Baseline and Day 90 | Change from baseline to Day 90 in complete blood count, blood glucose, calcium, electrolytes, total protein, albumin, alkaline phosphatase, bilirubin, blood urea nitrogen, creatinine, AST, ALT, and estimated glomerular filtration rate (eGFR). |
| Change from baseline in vital signs at Day 90. | Baseline and Day 90. | Change from baseline to Day 90 in systolic and diastolic blood pressure, pulse rate, respiration rate, and body temperature. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in percentage of HbF-positive cells. | Baseline, Day 30, Day 60, Day 90. | — |
| Change in HbF content in Red Blood Cells. | Baseline, Day 30, Day 60, Day 90. | — |
| Change in percentage of circulating irreversibly sickled cells. | Baseline, Day 30, Day 60, Day 90. | — |
| Change in hematocrit. | Baseline, Day 30, Day 60, Day 90. | — |
| Change in indirect bilirubin level. | Baseline, Day 30, Day 60, Day 90. | — |
| Change in reticulocyte count. | Baseline, Day 30, Day 60, Day 90. | — |
| Change in serum lactate dehydrogenase level. | Baseline, Day 30, Day 60, Day 90. | — |
| Change in ASCQ-Me Questionnaire (Adult Sickle Cell Quality of Life Measurement Information System) | Baseline, Day 30, Day 60, Day 90. | Questionnaire on acute and/or chronic pain, energy level, usage of pain medications and activity levels. |
| Change in pain intensity score. | Baseline, Day 30, Day 60, Day 90. | Evaluation of pain intensity for each body location (using a numeric pain rating scale from 0, no pain to 10 worst possible pain) |
| Change in pain relief score. | Baseline, Day 30, Day 60, Day 90. | Evaluation and evaluation of pain relief (pain relief scale in percent from 0%, no relief to 100% complete relief) |
| Occurrence of vaso-occlusive crises during the study | Day 0 to Day 90. | — |
Countries
India
Contacts
STUDY_DIRECTORMatthias CANAULT, PhD
LGD
Outcome results
None listed