Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication MAVENCLAD is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS [see Warnings and Precautions (5)… FDA label
Also known as Cladribine (MAVENCLAD®), Cladribine Low Dose, Mavenclad
Cladribine · 4 trials · 5 indications
To establish whether there is efficacy superiority of cladribine tablets over placebo in reducing deterioration of upper limb function in pwAMS. To investigate whether cladribine tablets 3.5mg/kg over 24 months is an effective DMT in pwAMS as measured using the 9-hole peg test (9HPT) peg speed at 24 months.
Area under the plasma concentration-time curve from zero to tau at steady state (AUCt,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.
Maximum observed plasma concentration in steady state (Cmax,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.
Minimum observed plasma concentration in steady state (Cmin,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.
Plasma concentration at end of dosing interval at steady state (Ctrough) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.
Time to reach the maximum observed plasma concentration at steady state (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel were reported. Calculated using descriptive statistics.
Average plasma concentration at steady state (Cav,ss) ) of Ethinyl Estradiol and Levonorgestrel were reported. Cav,ss =AUCt,ss/ tau, where, AUCt,ss was defined as the area under the plasma concentration-time curve in steady state during a complete dosing interval (tau) and Tau is the Complete dosing interval. Calculated using descriptive statistics.
The PTF within complete dosing interval at steady state, calculated as PTF (%) = (\[Cmax - Cmin\]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.
The maximum or peak plasma concentration observed after the administration of cladribine.
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | DBPC Period: Participants will be administered with Placebo, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5. BE Period: Participants initially randomized to placebo matched to cladribine in DBPC period will receive cladribine Low Dose or High Dose, orally as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated if clinically justified with placebo matched to cladribine. RT Period: If clinically justified, participants requiring retreatment with cladribine Low Dose or High Dose or cladribine supplemental dose will receive the selected dose of cladribine or matching placebo regimen. |
| Cladribine Low Dose | EXPERIMENTAL | DBPC Period: Participants will be administered with cladribine Low Dose, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5. BE Period: Participants initially randomized to cladribine Low Dose in DBPC period will receive placebo matched to cladribine as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated with cladribine supplemental dose if clinically justified. RT Period: If clinically justified, participants requiring retreatment with cladribine Low Dose regimen and/or supplemental dose will receive the selected dose of cladribine or matching placebo regimen. |
| Cladribine High Dose | EXPERIMENTAL | DBPC Period: Participants will be administered cladribine High Dose, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5. BE Period: Participants initially randomized to cladribine High Dose in DBPC period will receive placebo matched to cladribine as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated with cladribine supplemental dose if clinically justified. RT Period: If clinically justified, participants requiring retreatment with cladribine High Dose regimen and/or supplemental dose will receive the selected dose of cladribine or matching placebo regimen. |
| Cladribine (MAVENCLAD®) | ACTIVE_COMPARATOR | - |
| Sequence 1: First Cladribine, Then Placebo | EXPERIMENTAL | Period 1: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28. Period 2: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine matched Placebo along with Microgynon® from Day 9-14. From Day 15-28 participants received once daily Microgynon® along with 5-day once-daily Cladribine 10 to 20 mg depending on body weight. |
| Sequence 2: First Placebo, Then Cladribine | EXPERIMENTAL | Participants 5-day once daily Period 1: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine matched Placebo along with Microgynon® tablet once daily from Day 9-28. Period 2: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28. |
| Microgynon® | EXPERIMENTAL | Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle. |
| Cladribine followed by Cladribine + Pantoprazole | EXPERIMENTAL | Subjects will receive a single dose of cladribine10 milligram (mg) orally on Day 1. After a wash out period of 10-25 days, subjects will receive pantoprazole 40 mg orally for 2 consecutive days. On Day 2 of the pantoprazole administration, a single dose of cladribine 10 mg will be administered orally 3 hours after the second pantoprazole dose. |
| Cladribine + pantoprazole followed by Cladribine | EXPERIMENTAL | Subjects will receive pantoprazole 40 mg orally for 2 consecutive days. On Day 2 of the pantoprazole administration, a single dose of cladribine 10 mg will be administered orally 3 hours after the second pantoprazole dose. After a wash out period of 10-25 days, subjects will receive a single dose of cladribine 10 mg orally. |
| Name | Type | Description |
|---|---|---|
| Placebo | OTHER | Participants will receive placebo matched to cladribine in two courses separated by 4 weeks. |
| Cladribine Low Dose | DRUG | Participants will receive cladribine low dose in two courses separated by 4 weeks. |
| Cladribine High Dose | DRUG | Participants will receive cladribine high dose in two courses separated by 4 weeks. |
| Cladribine (MAVENCLAD®) | DRUG | Cladribine (MAVENCLAD®) 3.5mg/kg, administered as weight-adjusted 10mg tablets in two treatment courses (12 months apart) lasting 8- 10 days each. Cladribine (MAVENCLAD®) 10mg available in blister packs of 1 tablet, 4 tablets and 6 tablets. |
| Cladribine | DRUG | Participants received cladribine once-daily for 5 consecutive days in treatment period 1 and 2. |
| Microgynon® | DRUG | Participants received Microgynon® tablet once daily for 21 days in treatment period 1 and 2. Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle in Run-in period. |
| Pantoprazole | DRUG | Subjects will receive a pantoprazole 40 mg orally for 2 consecutive days either in first or second intervention period. |
Inclusion Criteria: * Adults of ≥ 18 years of age at the time of signing the informed consent. * Diagnosis of Myasthenia Gravis with generalized muscle weakness, meeting clinical criteria for Myasthenia Gravis Foundation of America Class II to IVa classification. * In participants positive for A...
Cladribine is used to treat multiple sclerosis, including relapsing multiple sclerosis and advanced multiple sclerosis, and is being studied in generalized myasthenia gravis. It is a small molecule immunology therapy developed by Merck KGaA. In myasthenia gravis, a new oral formulation is being tested against placebo.
Cladribine is developed by Merck KGaA, which trades under the ticker MKGAF. The company is running clinical development of the drug across multiple sclerosis and generalized myasthenia gravis, including a Phase 3 study of a new oral formulation in myasthenia gravis.
Cladribine is in clinical development, with a Phase 3 trial in generalized myasthenia gravis and a Phase 2 trial in advanced multiple sclerosis. It is investigational and is not described as approved in the supplied information. Phase 1 drug interaction studies have been completed.
Cladribine is being studied in NCT06463587, a recruiting Phase 3 trial of a new oral formulation versus placebo in generalized myasthenia gravis, and NCT04695080, an active Phase 2 trial in advanced multiple sclerosis. Completed Phase 1 studies include NCT03745144 and NCT00938366.
Yes, Cladribine is also known as MAVENCLAD and as Cladribine Low Dose. These names refer to the same small molecule immunology therapy developed by Merck KGaA, which is being evaluated in multiple sclerosis and generalized myasthenia gravis.